Laboratory Methods of Organic Chemistry - Sciencemadness Dot Org
Laboratory Methods of Organic Chemistry - Sciencemadness Dot Org
Laboratory Methods of Organic Chemistry - Sciencemadness Dot Org
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L A B O R A T O R Y M E T H O D S<br />
OF<br />
O R G A N I C C H E M I S T R Y<br />
BY<br />
L. GATTERMANN<br />
COMPLETELY REVISED BY<br />
HEINRICH WIELAND<br />
TRANSLATED FROM<br />
THE TWENTY-FOURTH GERMAN EDITION<br />
BY W. MCCARTNEY, PH.D.(EDIN.), A.I.C.<br />
LATE ASSISTANT IN THE DEPARTMENT OF MEDICAL CHEMISTRY, UNIVERSITY OF EDINBURGH<br />
WITH 59 ILLUSTRATIONS IN THE TEXT<br />
NEW YORK<br />
THE MACMILLAN COMPANY<br />
1937
COPYRIGHT<br />
PRINTFD IN GEEAT BRITAIN<br />
BY R. & R. CLARK, LIMITED, EDINBUEGH
PEEFACE TO THE TWENTY-FOUKTH EDITION<br />
WHILE the student is being educated in preparative work it is<br />
necessary for him to acquire some knowledge <strong>of</strong> the incessant progress<br />
in the methods <strong>of</strong> organic chemistry and at the same time to<br />
become familiar with the most recent results <strong>of</strong> research work. For<br />
these reasons a series <strong>of</strong> changes had to be made when this new<br />
edition was prepared. In order not to increase the bulk <strong>of</strong> the book<br />
these objects have been attained by sacrificing examples (e.g. linolenic<br />
acid, crystal violet, Gattermann-Koch aldehyde synthesis)<br />
with which, from this point <strong>of</strong> view, it seemed possible to dispense.<br />
Of the newly included methods two may be mentioned here :<br />
analysis by chromatographic adsorption which has attained such<br />
great importance, and the ozonisation <strong>of</strong> unsaturated compounds by<br />
the recently well-developed procedure.<br />
The section on analytical methods has been completely rewritten<br />
because the development <strong>of</strong> organic chemistry has caused<br />
the macro-methods practised in the classic period, methods which<br />
required considerable amount <strong>of</strong> material, to come to be regarded as<br />
survivals. The candidate for the Doctor degree, we know, no longer<br />
has to acquire the art <strong>of</strong> carrying out combustions since he is rightly<br />
unwilling, in practising this art, to sacrifice relatively enormous<br />
amounts <strong>of</strong> pure substance, <strong>of</strong>ten laboriously obtained. On various<br />
grounds I doubt the advisability <strong>of</strong> including micro-analysis in<br />
general practical courses.<br />
During a period <strong>of</strong> two years we have obtained such good results<br />
in this laboratory with a procedure worked out, on the basis <strong>of</strong><br />
Pregl's method, by Dr. F. Holscher that I have included it in this<br />
book. For this procedure 20-30 mg. <strong>of</strong> substance are required.<br />
The position has been reached where the candidate for the Doctor
vi LABORATOKY METHODS OF ORGANIC CHEMISTRY<br />
degree who reaps from his investigation a harvest not altogether<br />
too scanty and too precious, again carries out himself the combustion<br />
<strong>of</strong> his substances.<br />
It will be understood that, in working out this " meso-analytical "<br />
method now recommended we have made use, not only <strong>of</strong> the fundamental<br />
principles <strong>of</strong> Pregl, but also <strong>of</strong> all practical and tested<br />
improvements <strong>of</strong> other authors. (I propose the term " mesoanalytical<br />
" instead <strong>of</strong> the clumsy " half-micro ".)<br />
A reprint <strong>of</strong> the English edition <strong>of</strong> the book has appeared, and<br />
I have by chance learned that it has been translated into Russian<br />
and already published in two very large editions in Soviet Russia.<br />
An Italian translation is in course <strong>of</strong> preparation.<br />
I again have to thank several colleagues for valuable suggestions.<br />
In particular I have to thank Pr<strong>of</strong>. F. G. Fischer, Freiburg, and<br />
Dr. Elisabeth Dane, as well as my teaching assistant Dr. G. Hesse,<br />
for their active collaboration in the revision <strong>of</strong> the book. The<br />
pro<strong>of</strong>s have been corrected by T. Wieland.<br />
MUNICH, June 1935<br />
HEINRICH WIELAND
PEEFACE TO THE EEVISED (NINETEENTH)<br />
EDITION<br />
IT is rather more than thirty years ago since Ludwig Gattermann<br />
published the first edition <strong>of</strong> his Anleitungfiir das organisch-chemische<br />
Praktikum. The plan <strong>of</strong> providing the preparative directions with<br />
theoretical explanations has certainly proved satisfactory. That<br />
is already shown by the wide circulation <strong>of</strong> the book, <strong>of</strong> which<br />
eighteen editions have appeared. Methodology and technique are<br />
undoubtedly the chief objects <strong>of</strong> the practical course, but aiming<br />
merely at culinary art and technical achievement such a course<br />
does not accomplish enough. A command <strong>of</strong> methods implies above<br />
all an understanding <strong>of</strong> their rationale and a power <strong>of</strong> adapting<br />
their numerous modifications to particular requirements; the<br />
architect is more important than the mason. We demand that<br />
the student should be conversant with the theory <strong>of</strong> the transformations<br />
which he carries out practically. The comments made<br />
on the individual preparations are intended to facilitate a survey<br />
<strong>of</strong> the subject in hand, and to encourage the use <strong>of</strong> text-books<br />
and journals by further reading. Now that a knowledge <strong>of</strong> the<br />
principles <strong>of</strong> organic chemistry may be assumed during the preparative<br />
work in German universities, the danger <strong>of</strong> such comments<br />
becoming a pons asinorum is remote.<br />
In rewriting the book the theoretical and practical requirements<br />
have been deliberately increased. The equipment which sufficed<br />
during the last three decades has now become insufficient for those<br />
who desire to work at present-day problems, where difficulties<br />
have been accentuated alike in pure science and in technology.<br />
The idea <strong>of</strong> making the preparative work at once an explanation<br />
and a living experience <strong>of</strong> the science has demanded a rearrange-
viii LABOKATOKY METHODS OF ORGANIC CHBMISTEY<br />
ment <strong>of</strong> the subject matter in accordance with systematic relationships.<br />
It will be seen that the new arrangement does not depart<br />
seriously from the path which ascends from the more simple to the<br />
more difficult. In any case a considerable educational advantage<br />
may be expected to result from the rounding <strong>of</strong>f <strong>of</strong> successive subjects.<br />
The general part as well as the analytical have been completely<br />
revised and greatly shortened in order to make more space for the<br />
preparative part. The increase in the number <strong>of</strong> preparations is<br />
intended to provide variety, and to counteract a tendency towards<br />
stereotyped routine in the organic practical course.<br />
I am greatly indebted to my assistants, especially to Drs. Franz<br />
Bergel and F. Gottwalt Fischer, for untiring co-operation in carrying<br />
out numerous experiments. Dr. Fischer has, moreover, drawn the<br />
new diagrams for this edition and has prepared the index.<br />
FEEIBURG I. B., Master 1925<br />
HBINEICH WIBLAND
CONTENTS<br />
A. SOME GENERAL LABORATORY RULES<br />
Reaction Velocity and Temperature . . . . . .<br />
PAGE<br />
1<br />
Purification <strong>of</strong> <strong><strong>Org</strong>anic</strong> Substances . . . . . . 3<br />
Crystallisation . . . . . . . . 4<br />
Chromatographic adsorption . . . . . . 14<br />
Distillation . . . . . . . . . 15<br />
Sublimation . . . . . . . . . 26<br />
Distillation with Steam . . . . . . . 27<br />
Evaporation <strong>of</strong> Solvents . . . . . . . 29<br />
Extraction . . . . . . . . . 32<br />
Working with Compressed Gases . . . . . .35<br />
Heating under Pressure . . . . . . . 37<br />
Stirring and Shaking . . . . . . . . 38<br />
Determination <strong>of</strong> the Melting Point . . . . . . 40<br />
B. ORGANIC ANALYTICAL METHODS<br />
Detection <strong>of</strong> Carbon, Hydrogen, Nitrogen, Sulphur, and the Halogens . 43<br />
<strong><strong>Org</strong>anic</strong> Elementary Analysis . . . . . . 46<br />
I. Determination <strong>of</strong> Nitrogen by Dumas' Method . . .47<br />
II. Determination <strong>of</strong> Carbon and Hydrogen by Liebig's Method . 55<br />
III. Determination <strong>of</strong> Halogen, Sulphur, and other Elements . . 69<br />
1. Determination <strong>of</strong> halogen by the Carius method, p. 69; 2.<br />
Argentometric determination <strong>of</strong> chlorine and bromine, p. 73;<br />
3. Iodine determination by the Leipert-Munster method, p. 76;<br />
4. Determination <strong>of</strong> sulphur by the Carius method, p. 77; 5. Determination<br />
<strong>of</strong> sulphur by combustion, p. 78; 6. Simultaneous<br />
determination <strong>of</strong> halogen and sulphur, p. 79; 7. Determination<br />
<strong>of</strong> other elements, p. 79.<br />
IV. Determination <strong>of</strong> <strong><strong>Org</strong>anic</strong> Groups . . . . .80<br />
1. Volumetric determination <strong>of</strong> methoxyl and ethoxyl, p. 80;<br />
2. Determination <strong>of</strong> the acetyl and benzoyl groups, p. 82; 3.<br />
Determination <strong>of</strong> active hydrogen by the method <strong>of</strong> Tschugaeff<br />
and Zerevitin<strong>of</strong>f, p. 84.<br />
V. Determination <strong>of</strong> Molecular Weight . . . . .86
x LABOKATOKY METHODS OF OEGANIC CHBMISTEY<br />
C. PREPARATIVE PART<br />
On the Prevention <strong>of</strong> Accidents . . . . . .<br />
PAGE<br />
88<br />
Equipment required by the Beginner . . . . .90<br />
I. THE REPLACEMENT OF HYDROXYL AND HYDBOQEN BY HALOGEN.<br />
ALCOHOLS AND OLEITNES<br />
1. Ethyl bromide from ethyl alcohol . . . . .93<br />
• Methyl bromide, p. 95.<br />
2. Ethyl iodide from ethyl alcohol . . . . . . 95<br />
Methyl iodide, p. 96.<br />
3. Benzyl chloride from toluene . . . . . . 100<br />
4. Bromobenzene . . . . . . . . 103<br />
2>-Dibromobenzene, p. 105.<br />
5. Ethylene from ethyl alcohol. Ethylene dibromide . . . 107<br />
6. Glycol from ethylene dibromide . . . . . .114<br />
7. Isoamyl ether . . . . . . . .117<br />
8. Chloroacetic acid from acetic acid and chlorine . . . .118<br />
II. CAEBOXYLIC ACIDS AND THEIE SIMPLE DERIVATIVES<br />
1. Acid chlorides . . . . . . . . 121<br />
(a) Acetyl chloride, p. 121 ; (b) Benzoyl chloride, p. 121 ; Acetanilide,<br />
p. 125 ; Benzoyl peroxide, p. 125.<br />
2. Acetic anhydride . . . . . t. . 126<br />
3. Acetamide . . . . . . . . . 129<br />
Benzamide, p. 130.<br />
4. Urea and semicarbazide . . . . . . .131<br />
(a) Potassium cyanate by oxidative fusion, p. 131 ; (b) Urea, p. 132 ;<br />
(c) Semicarbazide, p. 134; (d) Urea (and uric acid) from urine, p. 135.<br />
5. Nitriles 137<br />
(a) Acetonitrile, p. 137 ; (b) Benzyl cyanide, p. 137.<br />
6. Hydrolysis <strong>of</strong> a nitrile to the acid. Phenylacetic acid . . 140<br />
7. Esters 141<br />
(a) Ethyl acetate from acetic acid and alcohol, p. 141, Ethyl benzoate,<br />
p. 141; (6) Isoamyl nitrite, p. 146, Ethyl nitrite, p. 147 ; (c) Ethyl<br />
nitrate, p. 148 ; (d) Hydrolysis <strong>of</strong> fat or vegetable oil, p. 149 ; Preparation<br />
<strong>of</strong> the free fatty acid, p. 150, Glycerol, p. 150; Analysis <strong>of</strong> fats,<br />
p. 151.<br />
8. Conversion <strong>of</strong> carboxylic acids into the next lower amines . .152<br />
(a) The H<strong>of</strong>mann reaction. Methylamine from acetamide, p. 152;<br />
(b) The Curtius reaction, p. 153, Benzoyl azide, p. 153, Phenyl<br />
cyanate, p. 153, Phenylurethane, p. 154.
CONTENTS x<br />
III. NlTBO-COMPOUNDS AND THEIR REDUCTION PRODUCTS<br />
1. Nitromethane . . . . . . .<br />
PAG]<br />
. 15(<br />
Methylamine, p. 158, N-Methylhydroxylamine, p. 158, Methylnitrolio<br />
acid, p. 158, Silver fulminate, p. 159, Phenylnitroethylene,<br />
p. 160.<br />
2. Nitration <strong>of</strong> an aromatic hydrocarbon . . . . .161<br />
(a) Nitrobenzene, p. 161; (b) Dinitrobenzene, p. 162.<br />
3. Reduction <strong>of</strong> a nitro-compound to an amine . . . . 16£<br />
(a) Aniline from nitrobenzene, p. 165, Diphenyltbiourea, Phenylisothiocyanate,<br />
p. 169; (b) m-Nitraniline from m-dinitrobenzene,<br />
p. 171.<br />
4. Phenylhydroxylamine . . . . . . . 174<br />
y-Aminophenol, p. 176, Nitrosophenylhydroxylamine, p. 177.<br />
5. Nitrosobenzene . . . . . . . . 17S<br />
Nitrosobenzene from aniline and Caro's acid, p. 179, Azobenzene<br />
from aniline and nitrosobenzene, p. 181, Azoxybenzene from phenylhydroxylamine<br />
and nitrosobenzene, p. 182.<br />
6. Hydrazobenzene and azobenzene . . . . . . 183<br />
(a) Hydrazobenzene, p. 183; (b) Azobenzene from hydrazobenzene,<br />
p. 184; (c) Benzidine from hydrazobenzene, p. 186. Mechanism <strong>of</strong><br />
the reduction <strong>of</strong> nitrobenzene, p. 188.<br />
IV. SeiiPHONic ACIDS<br />
1. Benzene monosulphonic acid from benzene and sulphuric acid . 191<br />
Diphenylsulphone, p. 191, Benzenesulphonyl chloride, p. 192,<br />
Benzenesulphonamide, p. 192, Benzenesulphohydroxamic acid, p.<br />
192.<br />
2. Toluene-p-sulphonic acid . . . . . . . 193<br />
3. Naphthalene-/?-sulphonic acid . . . . . . 194<br />
4. Sulphanilic acid from aniline and sulphuric acid . . . 195<br />
5. 2 : 4-Dinitro-a-naphthol-7-sulphonic acid (naphthol yellow S) . 195<br />
Thiophenol, p. 201.<br />
V. ALDEHYDES<br />
1. Formaldehyde . . . . . . . . 203<br />
Determination, p. 204.<br />
2. Acetaldehyde . . . . . . . . 205<br />
(a) From ethyl alcohol, p. 205 ; (b) from acetylene, p. 209.<br />
3. Benzaldehyde from benzylidene chloride . . . . 209<br />
Paraldehyde, p. 217, Metaldehyde, p. 217.<br />
•4. Cannizzaro's reaction. Benzoic acid and benzyl alcohol from<br />
.benzajdehyde . . . . . . . . 220
xii LABOKATOKY METHODS OF OEGANIC CHBMISTEY<br />
PAGE<br />
5. Acyloin condensation. Benzoin from benzaldehyde . . . 222<br />
Benzil from benzoin, p. 222, Benzilic acid, p. 225.<br />
6. Addition <strong>of</strong> hydrogen cyanide to an aldehyde. Mandelic acid from<br />
benzaldehyde . . . . . . . . 227<br />
7. Alanine 229<br />
8. Perkin's synthesis. Cinnamic acid from benzaldehyde and acetic<br />
anhydride . . . . . . . . 232<br />
Hydrogenation <strong>of</strong> cinnamic acid, p. 234, Sodium amalgam, p. 234.<br />
9. The Reimer-Tiemann synthesis. Salicylaldehyde from phenol and<br />
chlor<strong>of</strong>orm . . . . . . . . 235<br />
y-Hydroxybenzaldehyde, p. 236.<br />
VI. PHENOLS AND ENOLS. KBTO-ENOL TAUTOMERISM<br />
1. Conversion <strong>of</strong> a sulphonic acid into a phenol. /8-Naphthol . . 239<br />
Phenyl benzoate, p. 241, Naphthyl benzoate, p. 242, Tribromophenol,<br />
p. 242.<br />
2. Methylation <strong>of</strong> phenols . . . . . . . 244<br />
(a) Anisole, p. 244 ; (b) /3-Naphthyl methyl ether, p. 244.<br />
3. Ortho- and para-Nitrophenols . . . . . . 246<br />
4. Kolbe's salicylic acid synthesis . . . . . . 249<br />
5. Synthesis <strong>of</strong> the ester <strong>of</strong> a /?-keto-acid. Acetoacetic ester . . 251<br />
6. Acetylacetone . . . . . . . . 252<br />
Benzoylacetone, p. 253.<br />
7. Diethyl malonate . . . . . . . . 254<br />
Diethyl ethylmalonate, p. 254, Ethylmalonic acid, p. 255, Butyric<br />
acid from ethylmalonic acid, p. 255.<br />
8. Phenylnitromethane . . . . . . . 256<br />
(a) oct'-Phenylnitroacetonitrile sodium, f>. 256; (b) Sodium salt <strong>of</strong><br />
oct'-phenylnitromethane, p. 256.<br />
On keto-enol tautomerism . . . . . . . 257<br />
The use <strong>of</strong> ethyl acetoacetate and ethyl malonate for synthetic<br />
purposes . . . . . . . . 264<br />
VII. THE DIAZO-COMPOUNDS<br />
General . . . . . . . . . . 269<br />
A. Aliphatic Diazo-Compounds<br />
1. Diazomethane . . . . . . . .271<br />
Nitrosomethylurea, p. 271.<br />
2. Ethyl diazoacetate . . . . . . . . 275<br />
(a) Glycine ethyl ester hydrochloride, p. 275, Hippuric acid, p. 277 ;<br />
(b) Ethyl diazoacetate, p. 277.
CONTENTS xiii<br />
B. Aromatic Diazo-Compounds<br />
PAGE<br />
3. Diazotisation <strong>of</strong> aniline. Phenol, iodobenzene, and benzene from<br />
aniline. Isomerism <strong>of</strong> the diazo-compounds . . .281<br />
(a) Preparation <strong>of</strong> a solution <strong>of</strong> a diazonium salt, p. 281 ; (b) Conversion<br />
<strong>of</strong> the diazonium salt to phenol by boiling the solution, p. 282 ;<br />
(c) Iodobenzene from aniline, p. 283, Phenyl iodochloride, Iodosobenzene,<br />
Iodobenzene, p. 284; (d) Benzene from aniline, p. 285; (e) Solid<br />
phenyldiazonium chloride, p. 286, Phenyldiazonium nitrate, p. 287,<br />
Phenyldiazonium perbromide, p. 289, Phenyl azide, p. 289 ; (/) Sodium<br />
y-nitrophenyl-o»(t-diazotate, p. 290.<br />
4. p-Tolunitrile from p-tolnidine (Sandmeyer's reaction) .<br />
Benzonitrile, p. 292, y-Toluic acid, p. 292.<br />
. . 291<br />
5. Arsanilic acid from p-nitraniline . . . . . . 293<br />
6. Phenylhydrazine . . . . . . . . 296<br />
Benzene from phenylhydrazine, p. 299; Synthesis <strong>of</strong> indole, p. 299.<br />
7. Preparation <strong>of</strong> azo-dyes . . . . . . .<br />
(a) Helianthine, p. 300 ; (b) Congo red, p. 302 ; (c) /3-Naphthol orange,<br />
p. 303, Diazoaminobenzene and p-aminoazobenzene, p. 303.<br />
300<br />
On the coupling reaction <strong>of</strong> the diazo-compounds . . . 305<br />
VIII. QDINONOID COMPOUNDS<br />
1. Quinone from aniline . . . . . . . 309<br />
Quinol, p. 311, AnUinoquinone, p. 311, Quinhydrone, p. 314.<br />
2. p-Nitrosodimethylaniline . . . . . . . 314<br />
Dimethylamine and y-nitrosophenol, p. 316.<br />
3. ^-Aminodimethylaniline . . . . . . . 317<br />
Wurster's red, p. 319, Bindschedler's green, p. 321, Methylene blue,<br />
p. 322.<br />
4. Basic triphenylmethane dyes . . . . . . 324<br />
Malachite green from benzaldehyde and dimethylaniline, p. 324,<br />
Lead dioxide, p. 325.<br />
5. Fluorescein and eosin . . . . . . . 326<br />
Triphenylmethane dyes. Theoretical considerations . . . 327<br />
6. Alizarin 334<br />
IX. THE GRIGNARD AND FRIEDEL-CEAFTS SYNTHESES.<br />
ORGANIC RADICLES<br />
The Grignard Reaction<br />
1. Preparation <strong>of</strong> alcohols . . . . . . . 337<br />
(a) Benzohydrol from benzaldehyde and phenyl magnesium bromide,<br />
p. 337; (b) Triphenylcarbinol from ethyl benzoate and phenyl magnesium<br />
bromide, p. 338.<br />
2. Synthesis <strong>of</strong> a ketone from a nitrile. Acetophenone . . . 338
xiv LABOKATOKY METHODS OF OEGANIC CHBMISTEY<br />
The Friedel-Crafts Synthesis<br />
PAGE<br />
3. Synthesis <strong>of</strong> a ketone . . . . . . .343<br />
(a) Benzophenone from benzoyl chloride and benzene, p. 343; the<br />
Beckmann rearrangement, p. 344; (6) Acetophenone from benzene<br />
and acetic anhydride, p. 346.<br />
4. Triphenylchloromethane from benzene and carbon tetrachloride . 346<br />
5. 2 : 4-Dihydroxyacetophenone from resorcinol and acetonitrile . 347<br />
6. Quinizarin from phthalic anhydride and quinol<br />
<strong><strong>Org</strong>anic</strong> Radicles<br />
. . . 348<br />
7. Hexaphenylethane . . . . . . . . 352<br />
8. Tetraphenylliydrazine . . . . . . . 365<br />
Diphenylnitrosamine, p. 357.<br />
X. HBTEEOCYCIIC COMPOUNDS<br />
1. Pyridine derivatives . . . . . . . 361<br />
(a) Hantzsch's collidine synthesis, p. 361; (b) a-aminopyridine, p. 365.<br />
2. Quinoline . . . . . . . . . 366<br />
(a) Skraup's quinoline synthesis, p. 366 ; (b) Quinaldine synthesis <strong>of</strong><br />
Doebner and Miller, p. 367.<br />
3. Indigo . . . . . . . . . 369<br />
Phenylglycine, p. 369, Indoxyl fusion, p. 369, Indigo vat, p. 372,<br />
Dehydroindigo, p. 374.<br />
XI. HYDROGENATION AND REDUCTION. OZONJSATION<br />
1. Catalytic hydrogenation with palladium . . . . . 376<br />
Preparation <strong>of</strong> palladinised animal charcoal, p. 378; Preparation <strong>of</strong><br />
platinum oxide, p. 379.<br />
2. Catalytic hydrogenation with nickel. Cyclohexanol . . . 379<br />
Cyclohexane, p. 381.<br />
3. Replacement <strong>of</strong> the oxygen in carbonyl compounds by hydrogen.<br />
(Reduction by Clemmensen's method) . . . . 383<br />
(a) Ethylbenzene from aoetophenone, p. 383; (b) Dibenzyl from<br />
benzil, p. 383.<br />
4. Adipic aldehyde from cyclohexene by ozonisation . . . 384<br />
XII. NATURAL PRODUCTS<br />
1. Furfural . . . . . . . . . 386<br />
2. rf-Glucose from cane sugar . . . . . . 388<br />
3. Hydrolysis <strong>of</strong> cane sugar by saccharase . . . . . 388<br />
4. /?-Penta-acetylglucose and a-acetobromogluoose . . . 390
CONTENTS xv<br />
PAGE<br />
5. Lactose and casein from milk . . . . . . 391<br />
Ac'd hydrolysis <strong>of</strong> casein, p. 392.<br />
6. d-Galactose from lactose . . . . . . . 393<br />
Mucic acid, p. 393, Pyrrole, p. 393.<br />
7. Octa-acetylcellobiose and cellobiose . . . . . 394<br />
Some remarks on carbohydrates . . . . . . 395<br />
8. Saccharification <strong>of</strong> starch and alcoholic fermentation . . 401<br />
9. d-Arginine hydrochloride from gelatin . . . . . 404<br />
10. Caffeine from tea . . . . . . . . 406<br />
11. Nicotine from tobacco extract . . . . . . 406<br />
12. Haemin from ox blood . . . . . . . 407<br />
Chromatographic adsorption <strong>of</strong> pigment from leaves . . . 410<br />
13. The chief constituents <strong>of</strong> ox bile . . . . .411<br />
Glycocholic acid, p. 411, Cholic acid, p. 412, Desoxychohc acid,<br />
Fatty acids, and Cholesterol, p. 413.<br />
Hints for using the Literature <strong>of</strong> <strong><strong>Org</strong>anic</strong> <strong>Chemistry</strong> . . . 419<br />
Preparations from the Original Literature . . . . . 422<br />
Table for Calculations in the Determination <strong>of</strong> Nitrogen . . 424<br />
INDEX . . . . . . . . . . 427
xvi LABOKATOKY METHODS OF OEGANIC CHBMISTEY<br />
ABBEBVIATIONS<br />
The abbreviations <strong>of</strong> the titles <strong>of</strong> journals are those employed in British<br />
Chemical Abstracts. The abbreviated title is followed by the year, volume<br />
number (in heavy type), and page.<br />
Amer. Chem. J.<br />
Annaien<br />
Ann. chim.<br />
Ber.<br />
= American Chemical Journal.<br />
=Justus Liebig's Annaien der Chemie.<br />
=Annales de chimie [et de physique].<br />
= Berichte der deutschen chemischen Gesellschaft.<br />
Ber. deut. hot. Ges. = Berichte der deutschen botanischen Gesellschaft.<br />
Bull. Soc. chim. = Bulletin de la Soci6te chimique de France.<br />
Chem. Fabr. = Die chemische Fabrik.<br />
Chem. News = Chemical News.<br />
Chem. Zentr. = Chemisches Zentralblatt.<br />
Chem.-Ztg. = Chemiker-Zeitung.<br />
Compt. rend. =Comptes rendus hebdomadaires des seances de l'Academie<br />
des Sciences.<br />
Helv. Chim. Acta =Helvetica Chimica Acta.<br />
J. Amer. Chem. Soc. = Journal <strong>of</strong> the American Chemical Society.<br />
J.C.S.<br />
= Journal <strong>of</strong> the Chemical Society.<br />
J. pr. Chem. = Journal fur praktische Chemie.<br />
J.S.C.I.<br />
= Journal <strong>of</strong> the Society <strong>of</strong> Chemical Industry.<br />
Mikrochem. =Mikrochemie.<br />
Monatsh. =Monatshefte fur Chemie und verwandte Teile anderer<br />
Wissenschaften.<br />
Eec. trav. chim. =Recueil des travaux chimiques des Pays-Bas.<br />
Z. anal. Chem. = Zeitschrift fur analytische Chemie.<br />
Z. angew. Chem. = Zeitschrift ftir angewandte Chemie.<br />
Z. anorg. Chem. = Zeitschrift fur anorganische und allgemeine Chemie.<br />
Z. Elektrochem. =Zeitschrift fur Elektrochemie.<br />
Z. physikal. Chem. = Zeitschrift fur physikalische Chemie.<br />
Z. physiol. Chem. = Hoppe Seyler's Zeitschrift fur physiologische Chemie.
A. SOME GENERAL LABORATORY RULES<br />
Reaction Velocity and Temperature.—Eeactions with organic substances<br />
take place much more slowly than those which form the<br />
subject matter <strong>of</strong> a course <strong>of</strong> practical inorganic and analytical<br />
chemistry. The latter are nearly always ionic reactions, which<br />
proceed with immeasurable rapidity, but organic substances usually<br />
react much more slowly and therefore their preparation requires<br />
to be accelerated by increased temperature. A rise in the temperature<br />
<strong>of</strong> 10° doubles or trebles the velocity <strong>of</strong> most reactions. If the<br />
velocity at 20° is represented by v, then on the average that at 80°<br />
is vx2-5 6 . Consequently reactions will proceed in boiling alcohol<br />
about 250 times as fast as at -room temperature.<br />
For this reason many reactions <strong>of</strong> organic substances are<br />
brought about in heated solvents, usually at the boiling<br />
point.<br />
The vapour <strong>of</strong> the solvent is cooled in a condenser<br />
fixed on the reaction vessel in such a way that the<br />
evaporated solvent continuously flows back again.<br />
Tap water is passed through the condenser.<br />
In order to concentrate a solution the solvent is<br />
distilled "through a downward condenser". For this<br />
purpose various forms <strong>of</strong> coil condenser are more convenient<br />
than the Liebig pattern. For working " under<br />
reflux " such coil condensers are less suitable because<br />
<strong>of</strong> the layers <strong>of</strong> liquid which form in the coil between<br />
the vapour and the external atmosphere. A condenser<br />
designed by Dimroth has proved suitable for<br />
both types <strong>of</strong> work. In it the cooling water passes<br />
through the coil (Fig. 1). In order to prevent condensation<br />
<strong>of</strong> water vapour on the coil it is advisable<br />
FIG. 1<br />
to fix a calcium chloride tube into the upper opening <strong>of</strong> the condenser.<br />
If a solvent which boils above 100° is used, the water-cooled<br />
1 B
2 BXTBENAL COOLING<br />
condenser can be replaced by a long, wide glass tube (air condenser).<br />
The condenser is attached to the reaction vessel by means <strong>of</strong> a<br />
tightly fitting cork, which is s<strong>of</strong>tened in a cork-squeezer before being<br />
bored. The diameter <strong>of</strong> the cork-borer chosen should be less than<br />
that <strong>of</strong> the glass tube for which the hole is made. The borer is<br />
heated in the flame <strong>of</strong> a Bunsen burner and is driven in a strictly<br />
vertical position through the cork, which stands on the bench with<br />
the narrow end upwards. As far as is practicable, collodion should<br />
not be used for making stoppers gas-tight. In general, rubber<br />
stoppers should not be used in experiments in which they are exposed<br />
to the vapours <strong>of</strong> boiling organic solvents, since they swell greatly<br />
and also give <strong>of</strong>f soluble constituents which contaminate the reaction<br />
solution.<br />
The highest degree <strong>of</strong> purity is attained by using apparatus with<br />
standard ground joints (see e.g. Fig. 47); its sole disadvantage is<br />
its rather high price.<br />
External Cooling.—Many reactions which occur with great<br />
evolution <strong>of</strong> heat require to be moderated. Further, in the preparation<br />
<strong>of</strong> labile substances which might be damaged by a high<br />
temperature, it is <strong>of</strong>ten necessary to provide for the cooling <strong>of</strong> the<br />
reaction mixture. The degree <strong>of</strong> cooling varies and, depending on<br />
the amount <strong>of</strong> heat to be removed and on the reaction temperature<br />
necessary, is produced by running tap water (8°-12°), by ice,<br />
which is finely crushed and mixed with a little water, by an ice and<br />
salt mixture (0° to - 20°), or by a mixture <strong>of</strong> solid carbon dioxide<br />
with ether or acetone (down to -80°). Liquid air is generally<br />
not required in preparativp organic work. To prepare freezing<br />
mixtures such as are <strong>of</strong>ten required, ice, well crushed in an ice<br />
mill or metal mortar, is thoroughly mixed by means <strong>of</strong> a small<br />
wooden shovel with about one-third <strong>of</strong> its weight <strong>of</strong> rock-salt,<br />
preferably in a low, flat-bottomed glass jar or in a low enamelled<br />
saucepan.<br />
In order to keep a freezing mixture cold for hours (or even over<br />
night) it is transferred to a " thermos " flask, in which the contents <strong>of</strong><br />
test tubes pushed into the freezmg mixture can be maintained at<br />
low temperatures for a long time. For keeping larger vessels cold in<br />
this way, Piccard has indicated an arrangement easily constructed<br />
from two filter jars placed one inside the other. The bottom <strong>of</strong> the<br />
outer vessel is covered with kieselguhr until the rim <strong>of</strong> the centrally<br />
placed smaller jar is level with that <strong>of</strong> the outer jar. Then the
PUKIFICATION OF OEGANIC SUBSTANCES 3<br />
annular space between the jars is likewise packed with pressed down<br />
kieselguhr and its upper portion between the rims is tightly closed<br />
with pitch.<br />
Too little attention is generally paid to the concentrations <strong>of</strong> the<br />
reactants in preparative organic work. With the exception <strong>of</strong> rare<br />
cases (e.g. in intramolecular rearrangements) we are concerned with<br />
reactions <strong>of</strong> orders higher than the first, and in these several kinds<br />
<strong>of</strong> molecules—usually two—are involved. Since, according to the<br />
kinetic molecular theory, the velocity <strong>of</strong> bimolecular reactions is<br />
proportional to the number <strong>of</strong> collisions between the various dissolved<br />
molecules and therefore to the product <strong>of</strong> the concentrations,<br />
v = CA.CB.K (K = velocity constant),<br />
it is advisable in all cases where there is no special reason to the<br />
contrary to choose the highest possible concentration for a reacting<br />
solution.<br />
It should always be borne in mind that reduction <strong>of</strong> the concentration<br />
to one-half, one-quarter, or one-tenth makes the reaction<br />
four, sixteen, or one hundred times as slow.<br />
PURIFICATION OF ORGANIC SUBSTANCES<br />
The substances which form the object <strong>of</strong> preparative work are<br />
usually solid crystalline materials or liquids—occasionally also gases.<br />
Because <strong>of</strong> the multiplicity <strong>of</strong> reactions in which organic substances<br />
can take part, and in pronounced contrast to most reactions <strong>of</strong> inorganic<br />
chemistry, it is rare for an organic reaction to proceed<br />
strictly in one direction only and to yield a single end-product.<br />
Almost always secondary reactions occur and greatly complicate<br />
the isolation <strong>of</strong> pure homogeneous substances from a reaction mixture<br />
; this isolation constitutes the chief aim <strong>of</strong> preparative exercises.<br />
Sometimes several well-defined chemical compounds are produced<br />
at the same time and must be separated ; sometimes it is a question<br />
<strong>of</strong> separating the required substance with as little loss as possible<br />
from undesirable products which accompany it—the so-called resins<br />
or tars. These terms are used for by-products the origin and nature<br />
<strong>of</strong> which have usually not been investigated ; sometimes they unfortunately<br />
become the main product. As regards classical organic<br />
chemistry, they have awakened interest only in so far as they are<br />
regarded as an unmitigated nuisance.
4 CRYSTALLISATION<br />
The substances to be prepared must be freed very carefully from<br />
all these undesirable admixtures. For this purpose two methods<br />
are in principle available :<br />
1. Crystallisation<br />
2. Distillation<br />
1. CRYSTALLISATION<br />
General Considerations.—Solid crystallisable substances are<br />
usually obtained at the end <strong>of</strong> a reaction in the form <strong>of</strong> a crude<br />
product which separates in more or less pure form from the solvent<br />
on cooling, either directly or after concentration. The rate at<br />
which organic substances crystallise varies within very wide limits,<br />
and their tendency to form supersaturated solutions is extraordinarily<br />
great. But even when supersaturation is counteracted by<br />
dropping a crystal into the solution—by " seeding "—the attainment<br />
<strong>of</strong> equilibrium in the cold saturated solution is <strong>of</strong>ten exceedingly<br />
slow. The cause is indeed the slow rate <strong>of</strong> crystallisation.<br />
Hence the full yield <strong>of</strong> crude product is <strong>of</strong>ten obtained only after<br />
the solution has been left for many hours.<br />
The process <strong>of</strong> recrystallisation is most simply (and most frequently)<br />
carried out as follows : A hot saturated solution <strong>of</strong> the<br />
crude product in a suitable solvent is prepared, and from this<br />
solution the substance crystallises again in a purer condition. If<br />
the procedure is to succeed it is essential that the impurities should<br />
be more soluble than the substance itself, and should consequently<br />
remain dissolved in the cooled solution {the mother liquor).<br />
The principle <strong>of</strong> differential solubility is also applied conversely,<br />
namely, when the by-product can be separated from the just-saturated<br />
solution <strong>of</strong> the substance because <strong>of</strong> its low solubility in an<br />
appropriate solvent. Since, in this case, the solution always remains<br />
saturated with respect to the by-product, it is never possible<br />
by this method to obtain a substance in one operation, as may be<br />
possible by the first method.<br />
It is also important for recrystallisation from hot saturated<br />
solution that the temperature-solubility curve should rise as steeply<br />
as possible, i.e. that the dissolving power <strong>of</strong> the solvent should<br />
increase greatly with increasing temperature. In that case only<br />
can the amount <strong>of</strong> substance taken be recovered from the solution<br />
in the highest possible yield.
CHOICE OF SOLVENT 5<br />
The choice <strong>of</strong> the right solvent is therefore <strong>of</strong> great importance<br />
for the process <strong>of</strong> recrystallisation. The most commonly used<br />
solvents are the following : water, ethyl alcohol, methyl alcohol, ether,<br />
acetone, glacial acetic acid, ethyl acetate, benzene, petrol ether, chlor<strong>of</strong>orm,<br />
carbon bisulphide.<br />
For quite sparingly soluble substances, formic acid, pyridine,<br />
bromobenzene, nitrobenzene, and occasionally also phenol, ethyl<br />
benzoate, aniline, and dioxan are used. A distinct relation exists<br />
between the constitution <strong>of</strong> solute and solvent, and is expressed by<br />
the old rule : similia similibus solvuntur. Thus, as is well known,<br />
substances containing hydroxyl (e.g. sugars, carboxylic acids) are<br />
soluble in water, whereas hydrocarbons are more soluble in benzene<br />
and petrol ether than, for example, in alcohols.<br />
The above statements, however, generally hold with some degree<br />
<strong>of</strong> certainty for simple organic compounds only. With complicated<br />
substances the conditions are more involved, and unless the worker<br />
has long experience he is obliged to test the available solvents<br />
seriatim. Alcohol is used most, and with this one usually begins;<br />
then perhaps water, benzene, and petrol ether. It may be said that,<br />
on the whole, <strong>of</strong> the more usual solvents, benzene, chlor<strong>of</strong>orm, and<br />
ether have a very great, petrol ether and water a moderate solvent<br />
power for organic substances. Although the validity <strong>of</strong> this rule is<br />
contravened by many substances, it nevertheless gives some indication<br />
for testing purposes. Thus if the sample is too sparingly<br />
soluble in alcohol a solvent from the first group is chosen; if it is too<br />
soluble, one from the second. In the case <strong>of</strong> sparingly soluble substances<br />
a higher boiling homologue <strong>of</strong> the same class is <strong>of</strong>ten chosen<br />
—in place <strong>of</strong> the lower alcohol, propyl or amyl alcohol, instead <strong>of</strong><br />
benzene, toluene or xylene—because the higher boiling point brings<br />
about increased solvent power.<br />
It very <strong>of</strong>ten happens that the preparation <strong>of</strong> a substance leads<br />
to an amorphous crude product, resinous or flocculent, which becomes<br />
crystalline on digestion with a suitable solvent or else by<br />
direct recrystallisation. It must be remembered that the solubilities<br />
<strong>of</strong> the amorphous and crystalline forms <strong>of</strong> the same substance are<br />
altogether different, and that the amorphous preparation is always<br />
much the more soluble.<br />
Salts dissolve quite generally with ease in water, and <strong>of</strong>ten also<br />
in the alcohols, acetone, and chlor<strong>of</strong>orm, but they are not dissolved<br />
by ether, benzene, or petrol ether. Consequently organic acids can
6 CKYSTALLISATION<br />
be extracted by aqueous solutions <strong>of</strong> alkali, and organic bases by<br />
aqueous solutions <strong>of</strong> acid, from a mixture <strong>of</strong> neutral substances in<br />
a solvent like ether.<br />
When a substance has not the necessary moderate solubility in<br />
any solvent but is either too readily or too sparingly soluble, the<br />
combination <strong>of</strong> different solvents is a useful expedient. The solvents<br />
which are used together must be miscible with each other. The<br />
following are most frequently used :<br />
Alcohol, glacial acetic acid, acetone with water.<br />
Ether, acetone, benzene, chlor<strong>of</strong>orm with petrol ether.<br />
Pyridine with water, ether, or alcohol.<br />
The method <strong>of</strong> procedure is to add the solvent used as diluent<br />
drop by drop to the cold or hot concentrated solution until turbidity<br />
is just produced ; crystallisation is then induced by leaving<br />
the liquid to stand or by scratching with a sharp-edged glass rod.<br />
When crystallisation has begun the solution is cautiously diluted<br />
further. It is a mistake to precipitate the dissolved substance at<br />
one stroke with large amounts <strong>of</strong> the diluent.<br />
In the case <strong>of</strong> all operations which are not yet under control, 'preliminary<br />
test-tube experiments should be carried out. The student<br />
should acquire the habit <strong>of</strong> doing this from the very beginning.<br />
Aqueous nitrates should be collected in beakers, but organic<br />
solvents in conical flasks, which prevent evaporation and so check the<br />
formation <strong>of</strong> crusts. Already in order to obtain some idea <strong>of</strong> the<br />
degree <strong>of</strong> purity from the appearance <strong>of</strong> the crystals, the crystallisation<br />
should be left to go on undisturbed so that crystals may separate<br />
in the best possible form. It is an error to assume that fine crystals<br />
produced by immediate strong cooling <strong>of</strong> a solution constitute an<br />
especially pure substance ; on the contrary, the large surface <strong>of</strong> the<br />
deposit favours the adsorption <strong>of</strong> by-products. Moreover, with wellformed<br />
crystals it is much easier for the organic chemist to meet<br />
the imperative requirement that he should check the homogeneity<br />
<strong>of</strong> a substance. The examination <strong>of</strong> the preparation with a lens<br />
or under the microscope should not be neglected ; 50- to 100-fold<br />
magnification is sufficient.<br />
If a solution has become saturated at room temperature the<br />
yield <strong>of</strong> crystals can be increased by placing the vessel in ice-water<br />
or in a freezing mixture.<br />
Substances <strong>of</strong> low melting point occasionally separate as oils<br />
when their hot saturated solutions are cooled. The solution must
DISSOLVING THE SUBSTANCE<br />
then be diluted somewhat. Moreover, in such cases provision is<br />
made for slow cooling by standing the flask containing the solution in<br />
a large beaker <strong>of</strong> water at the same temperature and leaving till cold<br />
or wrapping a towel round it. Of substances which crystallise with<br />
difficulty a small sample should always be retained for use as<br />
" seeding " crystals. Separation as an oil may then be obviated by<br />
dropping these crystals into the solution before it has become quite<br />
cold and rubbing with a glass rod.<br />
Procedure.—In order to prepare a hot saturated solution the<br />
substance to be purified is covered, preferably in a short-necked,<br />
round-bottomed flask, with a little solvent which is then heated to<br />
boiling. More solvent is gradually added in portions until all the<br />
substance has dissolved. Since crude substances frequently contain<br />
insoluble impurities, the process <strong>of</strong> dissolution is carefully watched<br />
to see exactly if and when the compound to be recrystallised has<br />
completely dissolved. On account <strong>of</strong> the lability <strong>of</strong> many substances<br />
prolonged boiling is to be avoided. Solutions made with<br />
solvents which boil under 80° are prepared on the boiling water bath<br />
under reflux condenser; the solvent to be added may be poured<br />
into the flask through a funnel placed in the top <strong>of</strong> the condenser.<br />
It is better, however, at least when using large quantities, to fit a<br />
two-neck attachment (Anschiitz tube, Fig. 30, p. 39) to the flask,<br />
since in this way it is possible to add the solvent conveniently and,<br />
in other cases, to drop in solid substances also. The condenser is<br />
fixed in an oblique position to the oblique tube ~<br />
<strong>of</strong> the attachment, whilst the vertical tube,<br />
through which substances are added, is closed<br />
with a cork.<br />
Water and other solvents which boil above 80°<br />
are most suitably heated on an asbestos support<br />
in an air (Babo) oven or on an asbestos-wire<br />
gauze. If the boiling point lies considerably above<br />
that <strong>of</strong> water (more than 20°) the danger <strong>of</strong> cracking<br />
the condenser must be avoided by circulating<br />
warm water through it, or else the water condenser<br />
must be replaced by a long, wide glass »<br />
tube (air condenser), which may be wrapped in F 2<br />
moist filter paper if necessary. For test-tube experiments<br />
under reflux the so-called " cold finger " (Fig. 2) is exceedingly<br />
convenient. It consists <strong>of</strong> a glass tube about 15 cm. long
8 FILTKATION<br />
and from 6 to 8 mm. wide sealed at one end. About 3 cm. from<br />
the other end a narrow tube 3 cm. long is attached at a right angle<br />
and bent downwards so that the apparatus can be hung on an iron<br />
ring. Cooling water is led away through this side tube to which<br />
thin rubber tubing is attached. The water is led into the " cold<br />
finger " through a bent glass tube which reaches to the bottom and<br />
is fixed in a small piece <strong>of</strong> rubber tubing which acts as a stopper.<br />
This handy condenser is fitted into the test tube by means <strong>of</strong> a<br />
notched cork.<br />
The very troublesome " bumping " is avoided by adding porous<br />
pot, in pieces about half the size <strong>of</strong> a pea, before the boiling begins.<br />
When the pieces <strong>of</strong> pot become inactive they are replaced by new<br />
ones (do not drop them into superheated solutions !). When violent<br />
bumping occurs in large volumes <strong>of</strong> solution the addition <strong>of</strong> wooden<br />
rods is to be recommended.<br />
In order to remove coloured impurities, which <strong>of</strong>ten adhere<br />
tenaciously to a colourless substance, the hot saturated solution is<br />
boiled for a short time with a few knife-points <strong>of</strong> animal charcoal or<br />
specially prepared wood charcoal. Since the air which escapes from<br />
the charcoal causes copious frothing the adsorbent must be added<br />
carefully and with shaking. On account <strong>of</strong> their colloidal nature the<br />
coloured impurities are most easily adsorbed from aqueous solutions.<br />
Filtration.—Solutions from which crystals are to be obtained<br />
are not completely clear, even in the absence <strong>of</strong> charcoal, and they<br />
must therefore be filtered. A filter paper in the ordinary conical<br />
form is generally to be preferred to the " folded " paper. The<br />
angle <strong>of</strong> glass funnels is usually not quite correct, and allowance can<br />
be made for this by making the second fold in such a way that the<br />
straight edges <strong>of</strong> the paper do not quite coincide and then using the<br />
larger cone for the filtration.<br />
In preparative organic work readily permeable " grained " filter<br />
paper is alone <strong>of</strong> use.<br />
The dissolved substances (especially if the solution is very concentrated)<br />
<strong>of</strong>ten crystallises in the funnel on account <strong>of</strong> local cooling<br />
and in this way nitration is hindered. This trouble can be partially<br />
met by using a funnel (Fig. 3) with the delivery tube cut short<br />
(0-5-1-0 cm.). But it is much more satisfactory to use a so-called<br />
hot water funnel (Fig. 4) in which the filtering surface <strong>of</strong> the funnel<br />
is heated with boiling water in a metal jacket. When inflammable<br />
solvents are used, the flame must be extinguished before filtration.
ISOLATION OF CEYSTALS 9<br />
The steam-heated funnel (as in Fig. 5) is likewise very useful. When<br />
small amounts <strong>of</strong> liquid are to be filtered, the empty glass funnel may<br />
he heated over a naked flame before use, or the paper may be fixed<br />
FIG. 3 FIG. 4 FIG. 5<br />
in the funnel, moistened with alcohol, ignited, and allowed to burn<br />
till it begins to char, while the funnel is held in a horizontal position<br />
and rotated.<br />
It is <strong>of</strong>ten advisable, especially in the case <strong>of</strong> aqueous solutions<br />
which are difficult to filter, to use a porcelain Biichner funnel and<br />
apply suction. A well-fitting filter paper is required and the filter<br />
flask must be cautiously warmed before use, preferably by standing<br />
it in an enamelled pail <strong>of</strong> warm water and heating to boiling.<br />
If the filter paper becomes choked by crystallisation <strong>of</strong> the substance,<br />
it is best not to push, a hole through it. The paper should rather be<br />
held upright in a small beaker in which fresh solvent is kept boiling,<br />
and the more dilute solution thus obtained is poured through the same<br />
paper. In such cases the whole solution must generally be concentrated<br />
by evaporation.<br />
If it is desired to produce well-developed crystals when recrystallising,<br />
the filtrate, in which separation <strong>of</strong> crystals <strong>of</strong>ten occurs<br />
even during filtration, must be reheated till a clear solution is<br />
obtained and then allowed to cool slowly without being disturbed.<br />
The isolation <strong>of</strong> the crystals is never accomplished by ordinary<br />
filtration, but always by collecting them at the pump on a filter<br />
paper, or, in the case <strong>of</strong> concentrated acids and alkalis, on glass<br />
wool, asbestos, or, best <strong>of</strong> all, on Schott filters <strong>of</strong> sintered glass.<br />
Large amounts <strong>of</strong> substance are collected on Biichner funnels (Fig.<br />
6) <strong>of</strong> size appropriate to the quantity <strong>of</strong> the material to be separated.
10 FILTKATION<br />
It is quite wrong to collect a few grammes <strong>of</strong> substance on a funnel<br />
six or more centimetres in diameter. In many cases, especially for<br />
FIG. 6 FIG. 7<br />
small amounts (5 g. or less), the Witt filter plate (Fig. 7) is to be<br />
preferred. It presents the advantage that its cleanliness can be<br />
checked much more readily than that <strong>of</strong> an opaque porcelain funnel,<br />
and, especially, that much less solvent is required to wash the more<br />
compact solid.<br />
In order to prepare the filter paper a small piece <strong>of</strong> the paper is<br />
folded over the upper edge <strong>of</strong> the filter plate and then a piece having<br />
a radius 2-3 mm. greater is cut out with scissors. This piece is<br />
moistened with the solvent and fitted closely to the funnel by<br />
pressing, rubbing out small folds with a rounded glass rod or, in<br />
the case <strong>of</strong> larger plates, with the finger-nail.<br />
When minute amounts <strong>of</strong> substance (a few<br />
hundred milligrammes or less) have to be filtered,<br />
small glass plates 0-5-1 -0 cm. in diameter<br />
are used as supports for the filter paper. These<br />
plates are made from thin glass rods by heating<br />
one end in the blow-pipe till s<strong>of</strong>t and then<br />
pressing out flat on an iron or earthenware<br />
plate (Diepolder). The glass rods must be long<br />
enough and thin enough to pass through the<br />
delivery tube <strong>of</strong> a quite small funnel and to<br />
project beyond its end. The pieces <strong>of</strong> filter<br />
FIG. 8<br />
paper which rest on the glass plates are cut<br />
somewhat larger than the plates themselves and are made to<br />
fit closely (Fig. 8).
FILTKATION 11<br />
In order to remove the substance from the filter plate after filtration<br />
the funnel is inverted over a basin or watch-glass and all the material<br />
is transferred to the latter with the help <strong>of</strong> a thin glass rod or copper<br />
wire; the " glass button " is pushed out from its lower end. The plate<br />
is removed with forceps, but the paper not before it is dry. The<br />
material which adheres to the funnel is removed without loss by scraping<br />
with a small, obliquely cut piece <strong>of</strong> thin cardboard.<br />
The nitrate is collected in a filter flash <strong>of</strong> a size appropriate to<br />
the volume <strong>of</strong> the solution. The very useful filter tube (Fig. 8) in<br />
its various sizes is also employed when filtering on a small scale.<br />
Such tubes stand in a lead support or in a wooden block bored with<br />
holes <strong>of</strong> various diameters.<br />
In view <strong>of</strong> its great importance as a method for preparing<br />
analytically pure substances, the technique <strong>of</strong> filtration deserves<br />
the special attention <strong>of</strong> the student <strong>of</strong> practical organic chemistry.<br />
The process <strong>of</strong> pouring the crystals along with the mother liquor<br />
on to porous plate and subsequently washing is emphatically to be<br />
rejected. Already in the preparation <strong>of</strong> organic substances the<br />
mind <strong>of</strong> the beginner should, above all, be directed to working as<br />
much as possible in quantitative fashion. It is not the number <strong>of</strong><br />
preparations which indicate success, but the care and thoroughness<br />
with which each separate reaction is carried out.<br />
For these reasons the " mother liquor " must not be treated as<br />
waste and neglected. Its importance will indeed only become clear<br />
to the research worker, but the beginner at preparative work should<br />
extract from it whatever is to be extracted for his purposes.<br />
Filtrates are therefore reconverted into (cold) supersaturated<br />
solutions by evaporation <strong>of</strong> part <strong>of</strong> the solvent, and so a second<br />
crop <strong>of</strong> crystals is obtained. Occasionally yet another crop may be<br />
produced. As a rule the crops so prepared must be recrystallised<br />
once again from fresh solvent (check by melting point determination<br />
!).<br />
A few words should be added about the washing <strong>of</strong> crystalline<br />
precipitates with the object <strong>of</strong> freeing them from adherent mother<br />
liquor. The same solvent as was used for crystallisation must<br />
always be employed and, since its solvent power for the substance,<br />
even in the cold, leads to more or less appreciable loss, it must be<br />
used in the smallest possible amounts. Suction should not be applied<br />
while washing; the precipitate is saturated with the solvent and<br />
then the pump is turned on.
12 DEYING<br />
It is desirable to provide the Woulf bottle or filter flask, which should<br />
be connected to every water-jet pump, with a regulating cook which not<br />
only enables the suction to be cut <strong>of</strong>f conveniently but also allows <strong>of</strong><br />
|_|<br />
V<br />
changes in the partial vacuum, which are necessary in many<br />
cases.<br />
In the case <strong>of</strong> substances which are readily soluble even<br />
in the cold, the solvent used for washing must previously<br />
be cooled in a freezing mixture.<br />
As long as mother liquor adheres to the crystals, although<br />
it no longer drains from them, no air should be drawn<br />
through the material if volatile solvents are used. Otherwise<br />
the impurities in the mother liquor are also deposited,<br />
and, especially in the case <strong>of</strong> easily soluble substances, there<br />
is no certainty that these impurities can again be completely<br />
removed by washing.<br />
Small amounts <strong>of</strong> substances are washed with drops <strong>of</strong><br />
the solvent. A so-called dropping tube (Fig. 9), i.e. a glass<br />
tube drawn out to a not too narrow capillary, is used. Such<br />
tubes are also very convenient for carrying out many re-<br />
9 actions and they promote cleanliness in working.<br />
The practice, which may <strong>of</strong>ten be observed, <strong>of</strong> " purifying " substances<br />
by evaporating their solutions to dryness in a crystallising<br />
basin, or <strong>of</strong> leaving them till the solvent has evaporated, naturally<br />
does not achieve its purpose because, <strong>of</strong> course, the impurities are not<br />
removed in this way.<br />
Small amounts <strong>of</strong> precipitates which are difficult to filter are<br />
conveniently and rapidly separated by means <strong>of</strong> a small hand<br />
centrifuge.<br />
Drying <strong>of</strong> the Substances.—A pure preparation must be completely<br />
freed from adherent solvent. Stable substances are most<br />
conveniently dried at room temperature by exposure to the air for<br />
one or two days between sheets <strong>of</strong> filter paper laid on a clean support.<br />
Substances <strong>of</strong> high melting point are more rapidly freed<br />
from solvent in a drying oven or on the water bath ; some care is,<br />
however, always indicated.<br />
The method which is most certain, and the sole applicable to<br />
analytically pure preparations, consists in drying in a vacuum<br />
desiccator containing sulphuric acid. The old type <strong>of</strong> Scheibler is<br />
probably the most suitable.
VACUUM DESICCATOKS 13<br />
The consistency <strong>of</strong> the grease used to make the cover <strong>of</strong> the desiccator<br />
air-tight is very important; the most suitable grease is dry<br />
lanoline (adeps lanae anhydricus) or a mixture <strong>of</strong> equal parts <strong>of</strong> beef<br />
suet and vaseline. The tube carrying the stop-cock is moistened with<br />
glycerol and pushed through the rubber stopper previously fixed in<br />
the opening <strong>of</strong> the desiccator. Sharp edges on the tube must be rounded<br />
<strong>of</strong>f and care taken that an air-tight closure is made. The support inside<br />
the desiccator consists <strong>of</strong> a porcelain plate having three short legs and<br />
several circular openings into which small basins, watch-glasses, and the<br />
like can be fitted. In order to prevent the support from sliding to and<br />
fro, three suitably cut pieces <strong>of</strong> cork are firmly fixed between the rim<br />
and the walls <strong>of</strong> the desiccator. When air is admitted to the desiccator<br />
there is a danger that substances which are being dried may be blown<br />
about. To prevent this a stiff strip <strong>of</strong> cardboard, or similar object, is<br />
fixed against the inner opening <strong>of</strong> the tube. In addition, before the<br />
cock is opened, a strip <strong>of</strong> filter paper is held before the outer opening.<br />
This paper is then sucked in against the tube and sufficiently moderates<br />
the current <strong>of</strong> air.<br />
In order to dry the air which enters, a straight calcium chloride tube<br />
is attached to the tube <strong>of</strong> the desiccator. The calcium chloride must<br />
be firmly held in position at both ends by means <strong>of</strong> glass wool or, better,<br />
cotton wool. ID desiccators which are <strong>of</strong>ten carried about the container<br />
for the sulphuric acid is filled to the acid level with pieces <strong>of</strong> glass<br />
—small pieces <strong>of</strong> broken tube, stoppers, and the like—or with small pieces<br />
<strong>of</strong> pumice which have previously been boiled with dilute hydrochloric<br />
acid and then dried. Splashing is thus avoided. From time to time<br />
the concentrated sulphuric acid is renewed. A special vacuum desiccator<br />
must be kept for analytical work.<br />
For intensifying the drying effect, especially in respect <strong>of</strong> water,<br />
a small basin filled with solid technical potassium hydroxide is laid<br />
on the support. Most solvents, with the exception <strong>of</strong> chlor<strong>of</strong>orm,<br />
benzene, petrol ether, and carbon bisulphide, are absorbed by this<br />
combination. In order to free substances from these four solvents,<br />
thin slices <strong>of</strong> paraffin wax in a shallow basin are placed in the desiccator<br />
beside the substance, if its properties are such as to preclude<br />
drying in the air.<br />
The rule should be adopted that any vacuum desiccator which<br />
does not fully keep its vacuum over night (test with a gauge) should<br />
be discarded. Thus it is sufficient to evacuate once and to leave<br />
over night. To continue suction at the pump for hours is to waste<br />
water.<br />
Many substances contain water or other solvent so firmly bound<br />
that it cannot be removed in a vacuum at room temperature. These
14 DEYING IN A VACUUM<br />
are dried in a vacuum at a higher temperature; they are heated in a<br />
small round flask on the water bath or oil bath until they cease to lose<br />
weight. The so-called " drying pistol" (Fig. 10) is especially convenient<br />
for this purpose.<br />
The vapours from the liquid<br />
boiling in A heat the wide<br />
inner tube B, in which the<br />
substance is exposed in a<br />
porcelain boat. C contains<br />
a drying agent—for water<br />
and alcohol, phosphorus<br />
pentoxide, for other vapours,<br />
paraffin wax. According<br />
to the temperature<br />
desired, the heating liquid<br />
chosen is chlor<strong>of</strong>orm (66°),<br />
water (100°), toluene (111°),<br />
xylene (140°). C is connected<br />
to the pump.<br />
FIG. 10<br />
For drying small<br />
amounts <strong>of</strong> substance the copper drying block shown on p. 51 is<br />
greatly to be recommended.<br />
If a non-volatile solvent, such as glacial acetic acid, xylene, highboiling<br />
petrol ether, or nitrobenzene, has been used for recrystallisation,<br />
it is washed out before drying by means <strong>of</strong> one which is more<br />
easily removed, e.g. ether, benzene, petrol. In general a substance<br />
which is sparingly soluble in glacial acetic acid or nitrobenzene is so<br />
also in ether.<br />
Very finely divided precipitates and also those which choke the<br />
pores <strong>of</strong> the filter paper are separated from the liquid phase by<br />
means <strong>of</strong> a centrifuge.<br />
Chromatographic Adsorption. 1 —Coloured substances which cannot<br />
be separated from each other by crystallisation may be separated<br />
by the process known as chromatographic adsorption, a process<br />
which has been applied with great success during the last few years.<br />
Advantage is taken <strong>of</strong> the fact that the constituents <strong>of</strong> the mixture<br />
exhibit different affinities for adsorbents (alumina, talc, silica gel,<br />
sugar, calcium carbonate, calcium oxide), the solution <strong>of</strong> the mixture<br />
(usually an organic solvent is employed) being drawn through a<br />
1 M. Tswett, Ber. Deut. bot. Ges., 1906, 24, 234, 361, 384. Details <strong>of</strong> the method<br />
are to be found in the paper by A. Winterstein and G. Stein, Z. physiol. Chem., 1933,<br />
220, 247. See also Cook, J.S.C.I., 1936, 55, 724-726.
DISTILLATION 15<br />
filter tube filled with the adsorbent. The zones in which the<br />
separate constituents are fixed are demarcated by moving the unadsorbed<br />
material further down the column or washing it away<br />
altogether with a solvent other than that initially employed. As a<br />
result <strong>of</strong> this " development " a " chromatogram " (see Fig. 59) is<br />
obtained. After the column has been dried the zones are separated<br />
from each other mechanically and " eluted " with suitable solvents.<br />
Frequently colourless substances can also be separated and<br />
purified by this procedure provided that the chromatogram, prepared<br />
in a tube* <strong>of</strong> special glass or quartz, can be divided up in the<br />
light <strong>of</strong> a mercury vapour lamp, in accordance with the fluorescence<br />
induced. For example, carotene has thus been separated into three<br />
components (E. Kuhn, P. Karrer).<br />
A characteristic example <strong>of</strong> the application <strong>of</strong> this very modern<br />
method is described under chlorophyll (p. 410).<br />
2. DISTILLATION<br />
Purification by distillation consists in transferring the substance<br />
in the gaseous state to another place where it is again liquefied or<br />
solidified. Where this method <strong>of</strong> purification is used it is essential<br />
that the substance be stable at its boiling point. The latter can be<br />
lowered by distillation in a vacuum—at the pressure usually produced<br />
by the water-pump (12 mm.) the boiling point is on the<br />
average 100°-120° below that at atmospheric pressure. This difference<br />
is greater in the case <strong>of</strong> substances which boil above 250° at<br />
ordinary pressure. Very <strong>of</strong>ten, therefore, substances which do not<br />
distil unchanged at atmospheric pressure can be purified by distillation<br />
in a vacuum because they are thus exposed to a much<br />
lower temperature.<br />
Simple substances, and in particular those which are also readily<br />
volatile, such as hydrocarbons, alcohols, esters, the lower acids and<br />
amines, are distilled under atmospheric pressure. All substances<br />
which decompose easily, and those which have especially high<br />
boiling points, are distilled under reduced pressure. In general<br />
solid substances should only be distilled when purification by<br />
crystallisation has been unsuccessful on account <strong>of</strong> too great solubility<br />
or for other reasons. Naturally in each case the possibility<br />
<strong>of</strong> distillation (without decomposition) must be established in<br />
advance.
16 DISTILLATION<br />
Distillation, whether at atmospheric pressure or in vacua, serves<br />
not only to separate the product from non-volatile impurities but<br />
also to fractionate mixtures <strong>of</strong> volatile substances having different<br />
boiling points (fractional distillation).<br />
Distillation at Atmospheric Pressure.—The simple distilling flask<br />
with side tube sloping downward (Kg. 11) serves exclusively as the<br />
distilling vessel. In general the side tube should be attached<br />
high in the case <strong>of</strong> low-boiling liquids and nearer<br />
the bulb in that <strong>of</strong> less volatile liquids.<br />
The thermometer is held in the flask by means <strong>of</strong> a<br />
clean bored cork ; the bulb <strong>of</strong> the thermometer must be<br />
completely immersed in the vapour and hence must be<br />
below the junction <strong>of</strong> neck and side tube.<br />
Since the ordinary laboratory thermometers are <strong>of</strong>ten<br />
inaccurate, they must be compared<br />
with, a standard thermometer before<br />
use. The most accurate method <strong>of</strong><br />
standardisation is to hang the two<br />
thermometers side by side with the<br />
FIG. 11 bulbs dipping in concentrated sulphuric<br />
acid or paraffin at 250°, and then to<br />
observe the temperatures during cooling<br />
at intervals <strong>of</strong> 10° and record the deviations. Thermometers for<br />
distillations should have small bulbs so that they record rapidly.<br />
Distilling flasks should be chosen <strong>of</strong> such a size that the bulb is<br />
half or two-thirds full <strong>of</strong> liquid. In order to avoid bumping and<br />
superheating a few pieces <strong>of</strong> porous plate (pot) half as large as peas<br />
are dropped into the flask before each distillation. If boiling is<br />
again delayed fresh pieces <strong>of</strong> pot must be added, not to the superheated<br />
liquid, however, but after brief cooling.<br />
The flask is fixed above the side tube in a clamp lined with cork.<br />
Sources <strong>of</strong> Heat.—Liquids which do not boil above 80° are<br />
heated in the water bath (enamelled jar or beaker); the temperature<br />
<strong>of</strong> the bath should be about 20° above the boiling point <strong>of</strong> the substance.<br />
The maintenance <strong>of</strong> the correct heating temperature is <strong>of</strong><br />
the greatest importance, since if it is raised too much the boiling<br />
point <strong>of</strong> the distillate will be found too high in consequence <strong>of</strong><br />
superheating.<br />
In the case <strong>of</strong> substances <strong>of</strong> high boiling point where, for preparative<br />
purposes, a margin <strong>of</strong> a few degrees in the boiling point
BATHS AND CONDENSEKS 17<br />
may be allowed, a naked smoky gas flame may generally be used,<br />
which is at first cautiously made to play round the flask. A conical<br />
air bath (Babo) or wire gauze may likewise be used. When the<br />
substance is valuable, when attention must be paid to analytical<br />
purity, or also when, on account <strong>of</strong> the degree <strong>of</strong> stability <strong>of</strong> the<br />
substance, superheating should be avoided, it is preferable to use an<br />
oil or paraffin bath. For temperatures greater than 220° a bath <strong>of</strong><br />
Wood's or Rose's metal or a molten mixture <strong>of</strong> equal parts <strong>of</strong> potassium<br />
and sodium nitrates, both in an iron crucible, is to be preferred.<br />
Substances <strong>of</strong> low boiling point are condensed in a Liebig condenser<br />
attached to the side tube <strong>of</strong> the flask by means <strong>of</strong> a cork.<br />
If it is desired to avoid all loss by volatilisation, the condenser is<br />
connected to the filter flask serving as receiver by means <strong>of</strong> a socalled<br />
adapter and the receiver is cooled in ice, or else in a freezing<br />
mixture.<br />
For liquids which boil at about 100° a shorter condenser suffices,<br />
and when small amounts are being distilled it is especially advisable<br />
to use a small cooling jacket slipped firmly over the side tube so that<br />
loss <strong>of</strong> material is minimised. Such a device is illustrated in Figs.<br />
19 and 23.<br />
In the case <strong>of</strong> boiling points above 120° cooling with running<br />
water is generally not practicable, because the condenser tube, being<br />
in contact with the hot vapour, may easily crack; instead, the<br />
jacket contains as cooling agent standing water which gradually<br />
grows warm. When the boiling point exceeds 150° simple air cooling<br />
(wide condenser tube without jacket) suffices.<br />
Substances which solidify rapidly after condensation should<br />
never be distilled from a flask having a narrow side tube ; the distillate<br />
in the tube can indeed be reliquefied by warming with the<br />
flame, but <strong>of</strong>ten it is hardly possible to<br />
clear away the material which, blocks parts<br />
covered by corks or other connections, so<br />
that time is lost and annoyance caused.<br />
The sausage flask (Fig. 12) is therefore<br />
at once chosen. It has a wide side tube<br />
from which the product can be removed<br />
without trouble when distillation is com- • •„ ,2<br />
plete, preferably by melting.<br />
Normally distillation is carried out as follows. After the contents<br />
<strong>of</strong> the flask have been gradually heated, the visible signs <strong>of</strong><br />
c
18 DISTILLATION<br />
boiling appear, the mercury column <strong>of</strong> the thermometer rises rapidly<br />
and becomes steady at a definite temperature—the boiling point.<br />
When this temperature has been attained to within one degree the<br />
receiver (a small wide tube or similar vessel) for the first runnings is<br />
replaced by one suited to the amount <strong>of</strong> distillate expected (a conical<br />
flask or a narrow-necked bottle in which a small funnel is placed),<br />
and heating is continued at such a rate that one drop distils every<br />
second or every other second. The thermometer must be watched<br />
all the time. In general the boiling point range should not exceed<br />
l°-2°; in the case <strong>of</strong> analytically pure preparations the limits<br />
should be even closer. If a naked flame is used for distillation the<br />
boiling point rises a few degrees as a rule towards the end <strong>of</strong> the<br />
process on account <strong>of</strong> superheating, although pure substance is still<br />
passing over. If the boiling point rises even earlier, beyond the<br />
limit given, the receiver must be changed again and the distillation<br />
continued so that a third fraction, the " last runnings ", is collected.<br />
It should be borne in mind that both in the first and last runnings<br />
there is some <strong>of</strong> the main product. The vapour pressure <strong>of</strong> a distillable<br />
substance is so considerable even below the boiling point<br />
that its vapours already pass over along with the more volatile<br />
constituents (usually residues <strong>of</strong> solvent) <strong>of</strong> the original material.<br />
On the other hand the boiling point <strong>of</strong> a substance rises when it is<br />
mixed with higher boiling substances.<br />
Thus ether, which, is very extensively used to take up organic<br />
preparations, is not completely removed from a much less volatile substance<br />
even on the boiling water bath, although the boiling point <strong>of</strong> this<br />
solvent is 35°. The benzene wash <strong>of</strong> coke ovens is another well-known<br />
example which cannot be discussed in detail here.<br />
Hence it is evident that the last runnings also are not free from<br />
the main product, and when first and last runnings form an important<br />
amount it is worth while to redistil these two portions<br />
separately according to the rules given.<br />
Fractional Distillation.—When several volatile reaction products<br />
are to be separated from one another the procedure is not so simple<br />
as described above. In proportion as the boiling points <strong>of</strong> the<br />
various constituents approach each other the separation becomes<br />
more difficult, and it is not easy with the help <strong>of</strong> the usual laboratory<br />
apparatus to separate with any degree <strong>of</strong> precision substances which<br />
differ in boiling point by 10°.
FKACTIONAL DISTILLATION 19<br />
The nearest approach to the desired end is attained by repeating<br />
the process <strong>of</strong> distillation. In the case <strong>of</strong> low-boiling substances it<br />
can be done in one operation with the help <strong>of</strong> so-called fractionating<br />
columns, which are devices introduced into the gaseous phase before<br />
final condensation occurs. In the several divisions <strong>of</strong> these columns,<br />
which can be constructed in various forms (Fig. 13), vapours are<br />
liquefied by air cooling, and the vapours which are formed later<br />
must pass through this liquid which lies in their path. In this way<br />
FIG. 14<br />
the less volatile constituents <strong>of</strong> the vapour are condensed, while the<br />
more volatile are exposed to the same treatment in the next division.<br />
Thus a number <strong>of</strong> separate distillations corresponding to the number<br />
<strong>of</strong> bulbs in the column occurs, and if the operation is carried out<br />
carefully and slowly a far-reaching separation is made possible.<br />
Cylindrical columns irregularly filled with glass Easchig rings are<br />
especially suitable.<br />
The " Widmer spiral ", x shown in Fig. 14, has proved especially<br />
trustworthy. The smaller sizes are inserted into the lumen <strong>of</strong> the<br />
distilling flask and they render excellent service also in the fractional<br />
distillation <strong>of</strong> small amounts <strong>of</strong> substance.<br />
1 Widmer, Helv. Chim. Ada, 1924, 7, 59.
20 VACUUM DISTILLATION<br />
Technically the principle <strong>of</strong> fractional distillation is applied in the<br />
manufacture <strong>of</strong> spirit and in the isolation <strong>of</strong> aromatic hydrocarbons<br />
from the light oil <strong>of</strong> coal-tar.<br />
Mixtures <strong>of</strong> liquids <strong>of</strong> higher boiling point (above 120°) are first<br />
separated by distillation into several fractions <strong>of</strong> about the same<br />
boiling-point interval; the separate distillates (in smaller flasks) are<br />
again divided by distillation into fractions, and the fractions <strong>of</strong><br />
adjacent boiling points are then fractionally redistilled, while the<br />
boiling-point ranges are continually reduced. If, as is very advisable,<br />
the above-mentioned Widmer spiral is also used here, the<br />
column in which it is placed must be well lagged with asbestos.<br />
Not all mixtures are separable by distillation; occasionally<br />
substances which boil at different temperatures form constant boiling<br />
mixtures.<br />
Detailed information about the theory <strong>of</strong> fractional distillation<br />
will be found in J. Bggert, Lehrbuch der physikalischen Chemie,<br />
3rd Edition, 1931, p. 248.<br />
Vacuum Distillation.—The organic chemist must continually bear<br />
in mind that almost all substances with which he has to deal are,<br />
from the thermodynamical standpoint, metastable. In all cases,<br />
however, increased temperature favours the setting up <strong>of</strong> the true<br />
equilibrium—here decomposition—and hence it is appropriate to<br />
adopt the rule : Never endanger substances unnecessarily.<br />
Hence distillation under reduced pressure, whereby the boiling<br />
point can be reduced by one hundred and more degrees, acquires<br />
_ . great importance in organic work.<br />
11 1 The organic chemist who is doing<br />
^^ preparative work must quickly learn<br />
how to apply the method, and should<br />
early accustom himself to regard<br />
vacuum distillation not as in any<br />
way extraordinary, but as one <strong>of</strong><br />
the most elementary operations <strong>of</strong><br />
laboratory practice.<br />
The appropriate vessel for the<br />
distillation is the Claisen flask (Fig.<br />
-5<br />
15). The very practical division <strong>of</strong><br />
the neck into branches minimises<br />
the spurting <strong>of</strong> the boiling liquid, which is especially dangerous<br />
in this process. In order that the bumping, which very easily occurs
VACUUM DISTILLATION 21<br />
during vacuum distillation, may be avoided, minute bubbles <strong>of</strong> air,<br />
or in the case <strong>of</strong> substances sensitive to the action <strong>of</strong> air, bubbles <strong>of</strong><br />
hydrogen or carbon dioxide, are drawn continuously through the<br />
boiling liquid by means <strong>of</strong> a fine capillary tube.<br />
This tube is drawn out in the flame <strong>of</strong> a blow-pipe from glass<br />
tubing 4-8 mm. wide and is then drawn out again to sufficient fineness<br />
in a micro-flame. To make sure before use that the capillary is<br />
not closed, the tip is submerged in ether in a small test tube and air is<br />
blown in from the mouth. The bubbles should emerge separately<br />
and slowly. Capillaries for distillation in a high vacuum should emit<br />
air bubbles only on powerful blowing, and then with difficulty.<br />
Occasionally, and especially when liquids which foam are being<br />
distilled, it is necessary to regulate the amount <strong>of</strong> air passing through<br />
the capillary. To do this the capillary must not be too fine, and a<br />
small piece <strong>of</strong> new, thick-walled rubber tubing is fixed to the upper<br />
end <strong>of</strong> the tube and a screw clip is so attached that its jaws grip<br />
the rubber immediately above the glass. It must be borne in mind,<br />
however, that if the distillation is interrupted the liquid in the flask<br />
will be driven back by the external air pressure into the still evacuated<br />
capillary tube, and sometimes into the rubber tubing. This is<br />
avoided by cautiously unscrewing the clip before the interruption.<br />
When obstinate foaming occurs, the thermometer is discarded in<br />
favour <strong>of</strong> a second capillary tube in the front neck <strong>of</strong> the Claisen<br />
flask (6 in Fig. 15). The fine current <strong>of</strong> air drawn in through this<br />
tube bursts the bubbles <strong>of</strong> foam before they can pass over. 1<br />
The capillary tube is inserted (with a little glycerol as lubricant),<br />
tip first, into a narrow-bored, undamaged rubber stopper which fits<br />
tightly into the neck a <strong>of</strong> the Claisen flask. The correct position<br />
<strong>of</strong> the tip is immediately above the deepest part <strong>of</strong> the bulb <strong>of</strong> the<br />
flask. A thermometer, likewise pushed through a rubber stopper,<br />
is inserted into the neck b. If it is desired to prevent contact <strong>of</strong><br />
the substance with rubber, Claisen flasks with constricted necks are<br />
used. The capillary tube and thermometer are held in position in<br />
these necks by means <strong>of</strong> small pieces <strong>of</strong> rubber tubing drawn over<br />
each neck and its capillary or thermometer. The proper use <strong>of</strong><br />
cork stoppers in vacuum distillations requires much practice.<br />
The vapours are cooled in the way described ; here the use <strong>of</strong> the<br />
small water-cooling jacket drawn over the side tube is especially to<br />
be recommended. 1 E. Dorrer, Dissertation, Munich, 1926.
22 EBCBIVEES<br />
Receivers.—When only one or two fractions are expected, small<br />
filter tubes <strong>of</strong> suitable size, as illustrated in Fig. 8, are used (the<br />
smallest for the first runnings), or, in the case <strong>of</strong> larger amounts <strong>of</strong><br />
substance, small filter flasks. The rubber stoppers for attaching<br />
them should be tested in advance as to fit. When the receiver is<br />
being changed, the distillation must, naturally, be interrupted.<br />
If this is to be avoided and several fractions are expected, it is<br />
preferable to use an apparatus which permits various receivers to<br />
be brought successively under the mouth' <strong>of</strong> the delivery tube.<br />
The form shown in Fig. 16 may be used, for example. According<br />
to its shape it is known in laboratory slang as a " spider ", " frog ",<br />
" pigling ", or " cow's udder ".<br />
FIG. 16 FIG. 17<br />
Finally, Anschutz and Thiele's adapter with stop-cock (Fig. 17)<br />
may be mentioned ; it is very useful, in particular in the distillation<br />
<strong>of</strong> large amounts <strong>of</strong> substance. After the cocks a and b <strong>of</strong> this<br />
adapter have been closed the pressure in the receiver can be allowed<br />
to rise by unscrewing the clip c and the receiver can be changed.<br />
Then after c has again been closed and a vacuum has been reestablished<br />
throughout by opening 6, the cock a may also be opened<br />
and distillation continued. The third cock is not required. Of still<br />
simpler construction is the adapter (Fig. 18) with a three-way cock.<br />
By means <strong>of</strong> a boring in the cock the receiver can be opened to the<br />
atmosphere while the vacuum in the apparatus is maintained. After<br />
the receiver has been changed the cock must, however, be turned<br />
very cautiously, so that the distillate which has collected above is<br />
not blown out by air drawn in from below.
HEATING 23<br />
The two pieces <strong>of</strong> apparatus just described have the great advantage<br />
that the various fractions are at once completely isolated and<br />
do not come into contact with the vapours;<br />
on the other hand, they cannot be used for<br />
thick viscous liquids which do not pass<br />
through the boring <strong>of</strong> the cock.<br />
They are therefore <strong>of</strong> special use for<br />
the distillation <strong>of</strong> relatively low-boiling<br />
substances the vapour pressure <strong>of</strong> which<br />
cannot be neglected.<br />
When substances which solidify rapidly<br />
are distilled in a vacuum, the side tube <strong>of</strong><br />
the Claisen flask should be wide, as described<br />
for ordinary distillation.<br />
Heating. — Only after much practice<br />
can a vacuum distillation be carried out<br />
with a naked flame. Indirect heating in<br />
a bath is much more reliable. Here also<br />
FIG. 18<br />
the temperature <strong>of</strong> the bath should be adjusted with the greatest<br />
care to suit the boiling point <strong>of</strong> the substance (about 20° higher ;<br />
when the side tube is attached high up, the difference must be<br />
increased); when the boiling point <strong>of</strong> a fraction has been reached,<br />
the temperature <strong>of</strong> the bath should be kept constant.<br />
The flask is immersed in the bath to such a depth that the surface<br />
<strong>of</strong> the material to be distilled lies below that <strong>of</strong> the heating liquid.<br />
The bulb <strong>of</strong> the flask should not be more than half filled with substance.<br />
When high-boiling substances are distilled, the flask is immersed<br />
as deeply as possible and the portion above the bath to the junction<br />
with the side tube is wrapped in asbestos paper held in position by<br />
a thin wire or by a string.<br />
Sensitive substances which, as such, can be distilled in a vacuum,<br />
occasionally decompose when subjected abruptly while hot to large<br />
changes <strong>of</strong> pressure. In such cases the pressure is allowed to rise only<br />
after the contents <strong>of</strong> the flask have cooled. To proceed in this way is<br />
quite generally appropriate because thereby the very common oxidising<br />
action <strong>of</strong> hot air is also avoided.<br />
In all distillations under reduced pressure a small gauge (Kg. 19),<br />
introduced between pump and apparatus, is indispensable, since the<br />
pressure must be controlled throughout, in view <strong>of</strong> its effect on the
24 VACUUM DISTILLATION<br />
boiling point. Inconstant boiling points are very <strong>of</strong>ten due to<br />
variations in pressure. In order to hold back vapours which would<br />
contaminate the gauge by condensing in it, the cock is kept closed<br />
during the distillation, and only opened from time to time to test<br />
the pressure.<br />
Before every vacuum distillation the whole apparatus must be<br />
tested for tightness with the gauge, i.e. it must be shown to keep up a<br />
satisfactory vacuum.<br />
The heating <strong>of</strong> the bath is only begun after the vacuum has been<br />
produced. If the pressure over the already warmed liquid is reduced,<br />
it <strong>of</strong>ten froths over, owing to superheating. This may happen before<br />
the boiling point <strong>of</strong> the substance is reached : it is enough if the<br />
material still contains a little solvent, e.g. ether, the removal <strong>of</strong><br />
which on the water bath is never quite complete because <strong>of</strong> the<br />
greatly reduced vapour pressure.<br />
In many cases when readily volatile low-boiling substances are<br />
distilled in a vacuum it is necessary to reduce the volatility by<br />
raising the pressure. The full vacuum <strong>of</strong> the water pump, which,<br />
depending on the pressure and temperature <strong>of</strong> the tap water,<br />
amounts to 10-20 mm. <strong>of</strong> mercury, is then not used, but, instead,<br />
pressures <strong>of</strong> 20-100 mm. Since the action <strong>of</strong> the pump cannot be<br />
FIG. 19<br />
regulated, a cock attached to the Woulf bottle (a, Fig. 19) is used,<br />
so that with the help <strong>of</strong> the gauge any desired pressure can be<br />
obtained. For substances which boil above 150° under atmospheric<br />
pressure the maximum effect <strong>of</strong> the water pump is employed.<br />
The extent to which, the reduction <strong>of</strong> pressure in a vacuum distilla-
EFFECT OF PEESSUEE ON BOILING POINT 25<br />
tion lowers the boiling point can be seen in Fig. 20, in which nitrobenzene,<br />
boiling point 208°/760 mm. (curve I), and benzaldehyde (II),<br />
boiling point 179°/760 mm., are the examples chosen. The importance<br />
<strong>of</strong> a " good vacuum " in preparative work is expressed in the steep<br />
slope <strong>of</strong> the curves in the low-pressure region. When the distillation is<br />
carried out at 20 mm. the boiling point is about 15° higher than when<br />
the pressure is 10 mm. As the pressure rises this effect is reduced, as<br />
the curve III in the upper part <strong>of</strong> the figure makes clear. This curve,<br />
mmHg 20 3 2 10 BoiimB<br />
Point<br />
which is on a different scale, represents the region <strong>of</strong> pressure from<br />
760 mm. downwards. At Munich a reduction <strong>of</strong> the sea-level barometer<br />
to 720 mm. only lowers the boiling point <strong>of</strong> water by 1-5°.<br />
The quantitative relations between pressure and boiling point<br />
vary from substance to substance, but among organic compounds<br />
the variation is not very great, so that the curves here reproduced<br />
can in practice very well be used as a guide.<br />
For example, if according to the literature a substance boils at<br />
96°/l2 mm., it will boil at 104-105° at 18 mm.<br />
Substances which boil at too high a temperature, even in the vacuum<br />
<strong>of</strong> the water pump, can <strong>of</strong>ten be distilled without decomposition in a<br />
high vacuum, i.e. at pressures <strong>of</strong> 1 mm. or less. Reduction <strong>of</strong> pressure
26 SUBLIMATION<br />
to this limit reduces the boiling point on the average by 150° as compared<br />
with, the boiling point at atmospheric pressure, and by about 40°<br />
as compared with that in the vacuum <strong>of</strong> the water pump. The dotted<br />
continuation <strong>of</strong> the nitrobenzene curve I illustrates this—it is not<br />
based on actual measurements.<br />
Since the introduction <strong>of</strong> the so-called mercury vapour-jet pumps,<br />
which are to-day available in almost every university laboratory, distillation<br />
in a high vacuum presents no difficulty, and whoever has<br />
mastered ordinary vacuum distillation will also be able to distil in a<br />
high vacuum when the occasion arises, possibly when working according<br />
to directions from original literature. Because the apparatus is easily<br />
damaged, at least in ordinary usage, it has not been applied to the<br />
practical exercises in this book, and is not further described. The<br />
excellent mercury vapour-jet pump <strong>of</strong> Volmer should be available<br />
to-day in every organic teaching laboratory.<br />
Always protect the eyes during a vacuum distillation!<br />
SUBLIMATION<br />
Volatile substances <strong>of</strong> which the vapours, on cooling, condense<br />
directly to crystals without passing through the liquid phase are<br />
sometimes advantageously purified by sublimation, particularly<br />
when solubility relations render recrystallisation difficult. The<br />
purification <strong>of</strong> iodine is a well-known case in point. In organic<br />
chemistry this process is particularly suitable for quinones.<br />
Small amounts <strong>of</strong> substance are conveniently sublimed between<br />
two watch-glasses <strong>of</strong> equal size. The substance is placed on the<br />
lower glass and covered with a round filter paper, having several<br />
perforations in the centre, and somewhat larger than the glass. The<br />
second watch-glass is laid with its convex side upwards on the lower<br />
glass, and the two are fixed together with a watch-glass clip. When<br />
now the lower glass is heated as slowly as possible on the sand bath<br />
with a small flame the vapour from the substance condenses in<br />
crystals on the cold upper glass ; the filter paper prevents the<br />
small crystals from falling back into the hot lower glass. The<br />
upper watch-glass can be kept cool by covering it with several<br />
layers <strong>of</strong> moist filter paper or with a small piece <strong>of</strong> wet cloth.<br />
If it is desired to sublime larger amounts <strong>of</strong> substance, the upper<br />
watch-glass <strong>of</strong> the apparatus just described is replaced by a funnel,<br />
<strong>of</strong> which the diameter is somewhat less than that <strong>of</strong> the watch-glass.<br />
Sublimation can also be carried out in crucibles, flasks, beakers,
DISTILLATION WITH STEAM 27<br />
retorts, tubes, etc. If the substance to be purified only sublimes at<br />
a high temperature, as is the case, for example, with indigo or<br />
alizarin, a vacuum is applied (small round-bottomed flask or retort).<br />
When carrying out sublimations the student should always make<br />
sure that the apparatus has cooled completely before taking it apart.<br />
DISTILLATION WITH STEAM<br />
This important method <strong>of</strong> purification is very extensively used,<br />
both in the laboratory and on a large scale in chemical industry.<br />
It is based on the fact that many substances, the boiling points <strong>of</strong><br />
which may lie considerably above that <strong>of</strong> water, are volatilised by<br />
injected steam to an extent proportional to their vapour pressure at<br />
that temperature, and are then condensed along with the accompanying<br />
steam in a condenser. The most suitable and theoretically<br />
simplest case (see below) arises when the substance is sparingly<br />
soluble or practically insoluble in water.<br />
To test for volatility in steam, heat a small sample <strong>of</strong> the substance<br />
to boiling (porous pot!) in a test tube with about 2 c.c. <strong>of</strong> water and hold<br />
the bottom <strong>of</strong> a second test tube containing some ice in the issuing<br />
vapours until a drop <strong>of</strong> water has formed on the cold surface. A<br />
turbidity in the drop indicates that the substance is volatile with steam.<br />
The substance to be distilled is placed along with a little water<br />
in a capacious, long-necked, roundbottomed<br />
flask which should not<br />
be more than one-third filled, and<br />
is heated over a burner until near<br />
the boiling point (in order to avoid<br />
great increase in volume due to<br />
condensation <strong>of</strong> water). Then<br />
after the water has been turned on<br />
in the long condenser and the receiver<br />
has been placed in position,<br />
a rather vigorous current <strong>of</strong> steam<br />
is passed in. The wide steamdelivery<br />
tube should reach nearly<br />
to the bottom <strong>of</strong> the flask and<br />
should be bent slightly, as shown<br />
PIG. 21 V-—- -" -^<br />
in Fig. 21. If steam is not laid on in the laboratory it is produced<br />
in a tin can rather more than half filled and provided with a long
28 SUPBEHBATBD STEAM<br />
vertical safety tube. As a rule distillation is continued until the<br />
distillate passes over clear. If the substance crystallises in the<br />
condenser the jacket is partly emptied for a short time and the<br />
steam then melts the crystals, so that the substance flows away.<br />
Care must be taken, however, when this procedure is adopted,<br />
that there is no loss <strong>of</strong> uncondensed vapour carried away with the<br />
steam. The readmission <strong>of</strong> the cooling water to the hot tube must<br />
be done cautiously.<br />
When distillation is complete, the connection between the steam<br />
tube and the flask is broken before shutting <strong>of</strong>f the steam, because<br />
otherwise the residue in the flask might be sucked back through the<br />
inlet tube. Special attention must be paid to this point when the<br />
steam is taken from the laboratory supply.<br />
Smaller amounts <strong>of</strong> substance can also be steam distilled from a<br />
distilling flask <strong>of</strong> sufficient size having the side tube attached high<br />
up on the neck, and specially volatile substances can also be distilled<br />
by simple heating with water, without a current <strong>of</strong> steam.<br />
Substances which volatilise only with very great difficulty are distilled<br />
with superheated steam. The superheating takes place in a<br />
copper tube (Fig. 22) wound in a conical spiral, interposed between<br />
FIG. 22<br />
the steam generator and the flask and heated from below with a<br />
burner. The flask with the substance stands in an oil bath heated<br />
to a high temperature (about 150°).<br />
Sometimes the distillation can be performed without the superheater<br />
if the steam, dried as completely as possible, is passed, not<br />
too rapidly, into the distilling flask, containing the dry substance,<br />
which is kept hot in the bath. Volatile substances, which tend to<br />
decompose, are occasionally distilled with steam under reduced<br />
pressure and consequently at reduced temperature.
THEOKY OF STEAM DISTILLATION 29<br />
On the Theory <strong>of</strong> Steam Distillation.—The ideal case occurs when<br />
the substance to be distilled is insoluble, or, more accurately,<br />
sparingly soluble in water (examples: toluene, bromobenzene,<br />
nitrobenzene) so that the vapour pressures <strong>of</strong> water and the substance<br />
do not affect each other, or hardly so. The case <strong>of</strong> substances<br />
which are miscible with water (alcohol, acetic acid) is quite different<br />
and involves the more complicated theory <strong>of</strong> fractional distillation.<br />
Let us consider the first case only and take as our example bromobenzene,<br />
which boils at 155°. If we warm this liquid with water,<br />
its vapour pressure will rise in the manner shown by its own vapour<br />
pressure curve and independently <strong>of</strong> that <strong>of</strong> water. Ebullition will<br />
begin when the sum <strong>of</strong> the vapour pressures <strong>of</strong> the two substances<br />
has become equal to the prevailing atmospheric pressure. This is<br />
the case, as we can find from the vapour pressure curves, at 95-25°<br />
under a pressure <strong>of</strong> 760 mm.<br />
At this temperature the vapour pressure <strong>of</strong> bromobenzene<br />
amounts to 121 mm., that <strong>of</strong> water to 639 mm., and their sum consequently<br />
to 760 mm.<br />
According to Avogadro's rule, therefore, the vapour phase will<br />
contain the two components in the molecular ratio 121 : 639, i.e.<br />
there will be 5-28 times as many water molecules in the mixed<br />
vapour as molecules <strong>of</strong> bromobenzene. The absolute ratio in which<br />
bromobenzene passes over with steam is simply determined by<br />
taking the molecular weights into consideration. To 1 mole <strong>of</strong><br />
bromobenzene <strong>of</strong> molecular weight 157 there are 5-28 moles <strong>of</strong><br />
water <strong>of</strong> molecular weight 18, or, with 157 parts by weight <strong>of</strong> the<br />
first there distil 5-28 x 18 =95 parts by weight <strong>of</strong> the second. This<br />
corresponds to a ratio bromobenzene : water <strong>of</strong> about 5 : 3.<br />
Accordingly, if the vapour pressure curve <strong>of</strong> a substance not<br />
miscible with water is known, it is easy to calculate approximately<br />
its degree <strong>of</strong> volatility with steam. The calculation is approximate<br />
only because the condition <strong>of</strong> mutual insolubility is hardly ever<br />
fulfilled.<br />
On steam distillation under reduced pressure see p. 278.<br />
EVAPORATION OF SOLVENTS<br />
Since, during preparative organic work, substances have very<br />
<strong>of</strong>ten to be isolated from dilute solution, this operation is one <strong>of</strong> the<br />
commonest. Ether is distilled from the steam or water bath through
30 EVAPOKATION OF SOLVENTS<br />
a downward condenser (preferably a coil condenser) and is used<br />
again, possibly after purification. If it contains volatile acids it is<br />
shaken with dilute sodium carbonate solution ; if volatile bases are<br />
present it is shaken with dilute sulphuric acid.<br />
In order to avoid loss and conflagration due to the volatility <strong>of</strong><br />
the ether, a filter flask, connected to the condenser with a cork,<br />
is used as receiver, and a length <strong>of</strong> rubber tubing hanging down<br />
below the bench is attached to the side tube <strong>of</strong> the receiver for<br />
safety.<br />
Naked flames must never be allowed on the bench when work with<br />
ether or any inflammable solvent is in progress.<br />
If large amounts <strong>of</strong> solvent have to be evaporated, and if it is<br />
also desired to distil the dissolved substance after removal <strong>of</strong> the<br />
solvent, the solution is admitted from a dropping funnel, in portions,<br />
to a suitable distilling flask at the rate at which the solvent distils<br />
(porous pot). In this way the use <strong>of</strong> too large a vessel is avoided.<br />
If a steam bath is not available and a water bath has to be used, the<br />
flame must be extinguished each time the vessel is refilled (funnel!).<br />
In this case the process is usually more rapidly carried out by<br />
distilling the whole <strong>of</strong> the solvent from a large round-bottomed or<br />
conical flask and then washing the residue (completely!) with a little<br />
solvent into the smaller vessel.<br />
Small amounts <strong>of</strong> easily evaporated liquids can be removed<br />
directly from a test tube or a small flask heated on the water bath.<br />
On each occasion the test tube is filled to a depth <strong>of</strong> 2-3 cm. only,<br />
and is replenished from time to time; during the boiling on the<br />
water bath it must be shaken continuously or stirred with a thin<br />
glass rod. All preliminary tests with solutions are carried out in<br />
this simple way previous to an examination <strong>of</strong> the residues. For<br />
the latter purpose solutions <strong>of</strong> substances liable to decompose are<br />
left exposed to the air in watch-glasses or small crystallising basins<br />
so that the solvent may evaporate.<br />
When it is necessary to remove completely such solvents as<br />
alcohol or benzene it is not sufficient to use the steam or water bath<br />
alone, because the boiling point rises higher and higher as the concentration<br />
<strong>of</strong> the solution increases ; even ether causes difficulties.<br />
In this case, when the solvent ceases to distil, an oil bath or, more<br />
frequently, a vacuum is used. It is sufficient to mount a capillary<br />
tube, place the flask in a deep porcelain basin or in an enamelled<br />
basin maintained at a moderate temperature, and connect directly
EVAPOKATION IN A VACUUM 31<br />
to the pump ; this removes most solvents, water included, rapidly<br />
and completely.<br />
Thin-walled glass apparatus such as conical flasks, flat-bottomed<br />
flasks, and test tubes should never be evacuated.<br />
Round-bottomed flasks should always be employed, or, in<br />
certain cases, filter flasks, but the latter should only be warmed<br />
cautiously. If, as so <strong>of</strong>ten happens in the case <strong>of</strong> sensitive substances,<br />
large amounts <strong>of</strong> solvent have to be removed by distillation<br />
in a vacuum, condensation is accelerated by the use <strong>of</strong> a fairly large<br />
condenser and, where necessary, by cooling the receiver with ice.<br />
The condenser can be dispensed with if a simple distilling flask<br />
supported on a large funnel having a wide rubber tube attached to<br />
the stem is used as receiver. Water from the tap is kept pouring<br />
on the flask from above. The end <strong>of</strong> the side tube <strong>of</strong> the flask<br />
containing the material to be distilled must reach to the middle <strong>of</strong><br />
the bulb <strong>of</strong> the receiving flask. This arrangement is especially<br />
suitable for concentrating aqueous solutions.<br />
The arrangement illustrated in Fig. 23 permits <strong>of</strong> the continuous<br />
distillation in a vacuum <strong>of</strong> large amounts <strong>of</strong> liquid, in particular<br />
water. By operating the cock<br />
from time to time the liquid<br />
distilled can be replaced by suction<br />
from the storage vessel.<br />
The side tube should have as<br />
wide a bore as possible.<br />
The persistent foaming <strong>of</strong><br />
aqueous solutions during distillation<br />
frequently causes annoyance<br />
and loss <strong>of</strong> time. By<br />
adding to the solution about<br />
3 per cent <strong>of</strong> its volume <strong>of</strong><br />
FIG. 23<br />
isoamyl alcohol the trouble can be overcome. The aim is attained<br />
more certainly by drawing the solution into the empty flask, fixed<br />
ready for distillation, at the same rate as that at which the water<br />
distils. If this procedure is adopted it is advisable to draw out<br />
the end <strong>of</strong> the delivery tube to a narrow bore and to adjust the<br />
rate <strong>of</strong> flow from the storage vessel exactly by means <strong>of</strong> a screw<br />
clip (Fig. 23).
32 EXTKACTION<br />
EXTRACTION<br />
In order to extract from water a dissolved reaction product, or<br />
one which is not sufficiently solid or crystalline to be removed by<br />
filtration, or else to separate a substance from insoluble material<br />
which accompanies it, it is taken up in a suitable solvent. Ether<br />
is most commonly used for this purpose. Thus, for example, the<br />
distillate from a steam distillation is treated in this way unless it<br />
spontaneously separates into two layers.<br />
For the above purpose separating funnels are used. For small<br />
volumes (25 c.c. and less) funnels <strong>of</strong> the type shown in Fig. 24 are<br />
employed. The stems <strong>of</strong> these are at most 5 cm.<br />
long and are cut obliquely so as to facilitate delivery.<br />
A filter funnel is always used when pouring liquids<br />
into the separator. After the layers have separated,<br />
the lower is run <strong>of</strong>f through the cock and the upper<br />
through the upper opening. The cock is not opened<br />
until the heavier liquid has settled to the bottom,<br />
and, especially when ether is the liquid used for<br />
extraction, the pouring away <strong>of</strong> part <strong>of</strong> the aqueous<br />
solution along with the ether is to be avoided.<br />
Small preliminary samples are separated after being<br />
withdrawn from the main solution by means <strong>of</strong> a<br />
dropping tube (Fig. 9).<br />
FIG. 24<br />
Occasionally when aqueous solutions, and particularly<br />
suspensions, are extracted with an organic<br />
solvent very unpleasant emulsions make a clean separation impossible.<br />
The most effective way <strong>of</strong> avoiding this difficulty is to mix<br />
the liquids carefully. Further remedies are : creation <strong>of</strong> a vacuum<br />
in the separating funnel, addition <strong>of</strong> a few drops <strong>of</strong> alcohol, saturation<br />
<strong>of</strong> the aqueous phase with common salt, . . . and patience.<br />
If a substance is soluble in both water and the organic solvent,<br />
the result <strong>of</strong> the extraction depends on the ratio <strong>of</strong> solubilities ; if<br />
the " partition coefficient ", e.g. the ratio <strong>of</strong> the solubility in water<br />
to that in ether, is large, correspondmgly more ether must be used or<br />
the number <strong>of</strong> extractions must be increased. For this coefficient<br />
determines how a substance soluble in two immiscible solvents will<br />
distribute itself between them. Whether an aqueous solution should<br />
be extracted with a certain amount <strong>of</strong> ether in one portion or<br />
whether it is better to extract several times with smaller portions is
DEYING OF SOLUTIONS 33<br />
determined by the following simple consideration. Let us assume<br />
that the distribution coefficient is equal to 1, and that we have one<br />
volume <strong>of</strong> water and two <strong>of</strong> ether, which in the one case are used in<br />
one lot and in the other in two equal portions. Suppose that the<br />
amount <strong>of</strong> substance in solution is a grammes. Then in the first<br />
2o<br />
case the amount which passes into the ether is —, whilst in the<br />
o<br />
a<br />
second the first half <strong>of</strong> the total volume <strong>of</strong> ether takes up ^, and<br />
a a<br />
the second once again takes half <strong>of</strong> the remaining „ g-> i& -., mak-<br />
%a<br />
ing a total <strong>of</strong> — g. In order to extract this amount from water in<br />
one operation three volumes <strong>of</strong> ether would be necessary. This<br />
means that two lots <strong>of</strong> one litre used separately perform the same<br />
service as three litres used in one lot. The practical conclusion is<br />
obvious.<br />
The coefficient <strong>of</strong> partition <strong>of</strong> organic substances between water and<br />
lipins (these are fat-like constituents <strong>of</strong> the cell wall) is <strong>of</strong> great importance<br />
in biological processes (H. H. Meyer and Overton's theory <strong>of</strong><br />
narcosis).<br />
For the extraction from water <strong>of</strong> a dissolved substance, ethyl<br />
acetate, chlor<strong>of</strong>orm, benzene, amyl alcohol are also used occasionally<br />
instead <strong>of</strong> ether. Since water dissolves about 10 per cent <strong>of</strong> its<br />
volume <strong>of</strong> ether, unnecessary dilution is to be avoided, already for<br />
the sake <strong>of</strong> economy.<br />
The Drying <strong>of</strong> Solutions.—After a substance has been extracted<br />
from aqueous solution or suspension with an organic solvent its<br />
solution is saturated with water and must therefore be dried ; if<br />
drying were omitted, the dissolved water would mostly remain behind<br />
with the substance to be isolated, after the solvent had been evaporated.<br />
In choosing a drying agent it should be borne in mind that<br />
it must not react with the solvent nor with the solute, and must be<br />
completely insoluble in the former. The ethereal solution <strong>of</strong> a base<br />
may well be dried with solid potassium hydroxide, but, <strong>of</strong> course, not<br />
that <strong>of</strong> an acid. The most active and most commonly used drying<br />
agent is calcium chloride, which is used in either granulated or<br />
(previously) fused form; ethereal solutions are almost exclusively<br />
dried with it, except when they contain substances, such as alcohols<br />
D
34 EXTKACTION APPAEATUS<br />
and amines, which yield addition compounds with the salt. Ethereal<br />
solutions containing alcohol, should, therefore, never be dried with<br />
calcium chloride ; the alcohol must first be removed by repeated<br />
extraction with water. As a rule much too much drying agent is<br />
used. For ordinary purposes it is sufficient to use so much calcium<br />
chloride that after some time there remains, along with saturated<br />
calcium chloride solution, about an equal amount <strong>of</strong> the solid salt.<br />
Anhydrous sodium sulphate, even when freshly ignited before<br />
use, is much less active than calcium chloride. It is used when a<br />
substitute for calcium chloride is indicated for the reasons given<br />
above. For solutions <strong>of</strong> basic substances ignited potassium carbonate,<br />
solid potassium hydroxide, and barium oxide are much used<br />
as drying agents.<br />
In order to free the usual solvents completely from water the<br />
following agents are used :<br />
For ether, benzene, and its homologues and petrol ether:<br />
sodium.<br />
For acetone, chlor<strong>of</strong>orm, ethyl acetate, carbon bisulphide:<br />
calcium chloride.<br />
The alcohols are freed from water by boiling under reflux for<br />
several hours with freshly ignited quick-lime and are then distilled.<br />
Solvents such as chlor<strong>of</strong>orm and carbon tetrachloride, which<br />
contain chlorine, should on no account be dried with sodium, because<br />
<strong>of</strong> the danger <strong>of</strong> explosion.<br />
Extraction Apparatus.—Very <strong>of</strong>ten an organic substance is so<br />
much more soluble in water than in ether and other solvents that<br />
shaking with a solvent even when repeated is ineffective. In such<br />
cases an apparatus for continuous extraction <strong>of</strong> solutions is used ;<br />
it should not be wanting in any organic laboratory. The apparatus<br />
<strong>of</strong> Schacherl (Fig. 25), which can be constructed from simple laboratory<br />
materials, indicates the principle involved. Still more convenient<br />
is the apparatus shown in Fig. 26. It likewise can be<br />
constructed in all dimensions from easily obtainable materials.<br />
This leads to a consideration <strong>of</strong> extraction apparatus for solid<br />
substances. The best known is that <strong>of</strong> Soxhlet, which is much<br />
used, especially for analytical purposes. For preparative work the<br />
simplified extractor (Fig. 27) is to be preferred, for it is cheaper and<br />
works more quickly. In order to prevent the formation <strong>of</strong> channels<br />
by the drops <strong>of</strong> solvent in the material to be extracted, a thin<br />
porcelain sieve-plate (filter-plate) is laid on top.
EXTKACTION APPAEATUS 35<br />
The extraction apparatus is used chiefly for dissolving out<br />
sparingly soluble constituents from mixtures, and for isolating<br />
natural products from (dry) vegetable or animal material. Occasionally<br />
it is very useful for " recrystallising " sparingly soluble<br />
substances from the extraction thimble by means <strong>of</strong> an appropriate<br />
solvent (especially ether). As a rule, crystals <strong>of</strong> the dissolved<br />
material separate already from the solution in the flask during the<br />
process <strong>of</strong> extraction. This solution soon becomes supersaturated<br />
even while hot.<br />
L<br />
FIG. 25 FIG. 26 FIG. 27<br />
When solvents <strong>of</strong> high boiling point are used the extraction<br />
thimble is directly suspended by a thin wire in the round-botomed<br />
flask, but should not dip into the liquid.<br />
WORKING WITH COMPRESSED GASES<br />
Nowadays every university laboratory is doubtless supplied with<br />
steel cylinders in which the most important gases in common use are<br />
stored in the compresed state.<br />
These gases are :<br />
(1) Oxygen, hydrogen, nitrogen.<br />
(2) Carbon dioxide, chlorine, ammonia, sulphur dioxide.
36 WOKKING WITH COMPKESSED GASES<br />
The elements under (1), with very low critical temperatures, are<br />
in the gaseous state in the cylinders, but the substances under (2) are<br />
present in liquid form. Oxygen, hydrogen, and nitrogen are usually<br />
under a pressure <strong>of</strong> 150 atmospheres in cylinders having a capacity<br />
<strong>of</strong> 10 litres; after filling, therefore, the cylinders contain gas sufficient<br />
to occupy 1-5 cubic metres at atmospheric pressure. The<br />
taps <strong>of</strong> the hydrogen cylinders have reversed screw threads so as to<br />
prevent accidental charging with oxygen.<br />
In the laboratory all cylinders should be fitted with reducing valves,<br />
for the maintenance <strong>of</strong> which an assistant should be responsible.<br />
The use by itself <strong>of</strong> the simple valve in the head <strong>of</strong> the cylinder makes<br />
regulation <strong>of</strong> the gas stream difficult and invariably leads to waste.<br />
For all gases (chlorine included) the so-called conical valve <strong>of</strong><br />
aluminium bronze can be used. It can be<br />
made cheaply by any skilled mechanic<br />
(Fig. 28).<br />
In all work with gases—whether from<br />
cylinders or from Kipp's apparatus — a<br />
means <strong>of</strong> gauging the velocity <strong>of</strong> the current<br />
must be used. Except with ammonia, a<br />
small bubbler containing concentrated<br />
sulphuric acid serves. It can be attached<br />
to the cylinder itself. As a rule, in order to<br />
dry at the same time, a wash-bottle is attached,<br />
preferably not one in two parts<br />
with a ground glass joint, because such<br />
bottles are <strong>of</strong>ten forced open by the slightest<br />
excess pressure. 1 If the gases have to be<br />
dried very thoroughly a wash-bottle with<br />
FIG. 28<br />
concentrated sulphuric acid is not sufficient,<br />
and one or two u-tubes containing phos-<br />
phorous pentoxide spread on glass wool are added. Ammonia is<br />
passed through potassium hydroxide solution 1 : 1 and is then dried<br />
by passage through a tower containing potassium hydroxide and<br />
calcium oxide.<br />
Ordinary laboratory apparatus cannot be used with, gas from a<br />
cylinder for carrying out reactions under pressure in a closed system.<br />
For example, if it is desired to leave a reaction solution under pressure<br />
1 After use the connection between steel cylinder and wash-bottle should always<br />
be broken so as to prevent sucking back <strong>of</strong> the sulphuric acid.
HEATING UNDEK PEESSUEE 37<br />
in hydrogen or carbon dioxide, the reaction vessel should not simply<br />
be left connected to the cylinder. In order to relieve the pressure in<br />
the apparatus the circuit includes a T-tube, one branch <strong>of</strong> which is<br />
connected to a glass tube dipping into a cylinder with mercury or<br />
water.<br />
In such cases it is more convenient to use a Kipp or, when nitrogen<br />
is employed, a gas-holder filled from a cylinder.<br />
Experience shows that much gas is wasted because the beginner<br />
rarely considers how much is approximately required for his reaction.<br />
Nevertheless he should do so.<br />
With the exception <strong>of</strong> nitrogen, all commonly used gases can,<br />
if necessary, be prepared by simple, well-known methods.<br />
HEATING UNDER PRESSURE<br />
When it is desired to accelerate a reaction in solution or with<br />
undissolved substances at a temperature above their boiling point,<br />
the reactants must be shut <strong>of</strong>f from the external atmosphere either<br />
by sealing in a glass tube in which they are then heated, or in a closed<br />
metallic vessel (autoclave). This is obviously necessary even when<br />
we wish a reaction to take place in alcoholic solution at 100° or in<br />
aqueous solution at about 120°. Thus the aim is entirely to increase<br />
the temperature <strong>of</strong> the reaction; the accompanying increase in<br />
pressure has no effect on the reaction velocity, for as a rule it is unaccompanied<br />
by any significant change in the concentration.<br />
Since solutions are most frequently heated in sealed tubes in<br />
which the vapour pressure <strong>of</strong> the solvent determines the pressure, it<br />
is necessary to reckon with quite considerable pressures at temperatures<br />
which are appreciably above 100°. Gases which may<br />
possibly be formed during the reaction will add to the pressure. An<br />
estimate <strong>of</strong> the degree <strong>of</strong> pressure to be expected in a sealed tube<br />
reaction should be made with the help <strong>of</strong> the vapour pressure curve<br />
<strong>of</strong> the solvent used. In preparative reactions carried out in the<br />
heated tube, the pressure is always that <strong>of</strong> the saturated vapour.<br />
The pressure is therefore not dependent on the absolute amount <strong>of</strong><br />
the solution taken. But since particularly water in the liquid state,<br />
and hence also solvents containing water, attack glass seriously at<br />
high temperatures, the tube is generally not more than half rilled.<br />
Naturally when a gas is produced during the reaction the amount <strong>of</strong><br />
free space available for it plays a part in determining the ultimate<br />
pressure.
38 SEALED TUBES AND AUTOCLAVES<br />
The pressure tubes <strong>of</strong> Jena glass commonly used can be employed<br />
with some degree <strong>of</strong> certainty for pressures <strong>of</strong> 20 to 25 atmospheres<br />
if chemical action on the glass is excluded.<br />
Tubes for sealing should always be filled through a funnel, and<br />
the inner walls in the neighbourhood <strong>of</strong> the part to be sealed must<br />
be kept clean. Concerning the handling <strong>of</strong> sealed tubes see pp.<br />
70-71.<br />
If the temperature is not to be raised above 100° the tube is<br />
wrapped in a towel and suspended in a specially protected water<br />
bath by means <strong>of</strong> a string or wire.<br />
When no pressure or only slight pressure is developed a sodawater<br />
bottle with patent stopper is used instead <strong>of</strong> the sealed tube<br />
and is heated in the water bath.<br />
For preparative work sealed tubes are unsatisfactory because<br />
<strong>of</strong> their small capacity, and therefore for<br />
larger quantities <strong>of</strong> material autoclaves are<br />
used. These are metal vessels capable <strong>of</strong><br />
withstanding high pressures. The covers<br />
(see Fig. 29) are made tight with a lead<br />
ring, and are fastened by means <strong>of</strong> six<br />
to eight bolts, <strong>of</strong> which the nuts are<br />
gradually tightened in regular succession.<br />
Various types <strong>of</strong> autoclave are in use. That<br />
known as the Pfungst tube may be specially<br />
recommended. Autoclaves should<br />
always be heated in the oil bath.<br />
When carrying out pressure work always<br />
protect the eyes, and form in advance some<br />
physical idea <strong>of</strong> the strain imposed on the<br />
apparatus.<br />
STIRRING AND SHAKING<br />
In work with homogeneous solutions<br />
mechanical agitation is not necessary except<br />
when it is desired to add a substance<br />
in small portions or drop by drop, so as to<br />
IQ- bring it at once into a state <strong>of</strong> fine division,<br />
whether in solution or in suspension. This holds especially<br />
in cases where a sensitive preparation is endangered by the heat <strong>of</strong>
STIEEING AND SHAKING 39<br />
reaction locally developed, e.g. when concentrated sulphuric acid is<br />
added.<br />
In such cases the solution must be continuously agitated—by<br />
manual shaking or, better, by mechanical stirring. A glass rod,<br />
to the lower end <strong>of</strong> which propeller-like blades <strong>of</strong> glass are sealed,<br />
makes a suitable stirrer. Its upper end is slipped through a somewhat<br />
wider glass tube or cork-borer, which again is pushed through<br />
a cork, clamped so as to hold the stirrer vertically. To the upper<br />
end <strong>of</strong> the stirring rod a small pulley or a grooved cork or rubber<br />
stopper is firmly fixed. The rod should move with the least possible<br />
friction (in a narrow rubber ring smeared with glycerol). For driving,<br />
a Eabe water turbine is used or else a small suitably geared<br />
electro-motor (jg-th horse-power is sufficient). In places where<br />
there is no water supply the stirrer may be driven by a small hotair<br />
engine, such as that made by Heinrici <strong>of</strong> Zwickau, which is also<br />
excellent for other purposes.<br />
If the contents <strong>of</strong> a closed vessel have to be stirred or if the<br />
material is at the same time to be heated under reflux, a mercury<br />
seal must be provided on the stirrer, as<br />
shown in Fig. 30. Such a seal cannot,<br />
however, withstand<br />
inside the flask.<br />
pressure developed<br />
When liquids consisting <strong>of</strong> non-miscible<br />
layers are to be stirred the blades <strong>of</strong> the<br />
stirrer must work at the interface. Heavy<br />
deposits, e.g. zinc dust, sodium amalgam,<br />
are generally not moved about adequately<br />
by small glass stirrers. In such cases mechanical<br />
stirring is <strong>of</strong>ten illusory, and a<br />
more powerful effect is obtained manually<br />
by stirring with a glass rod or strip <strong>of</strong> wood,<br />
or by frequent shaking.<br />
The shaking machine must also be<br />
mentioned here; it is used to produce<br />
the finest possible mechanical division in<br />
heterogeneous systems. Narrow - necked<br />
bottles with well - fitting ground glass<br />
Fro> 30<br />
stoppers are almost exclusively used as containers. The stopper is<br />
held down by means <strong>of</strong> a piece <strong>of</strong> rubber tube drawn over it and<br />
fastened to the neck with thin wire. Unless appropriate safeguards
40 DETEKMINATION OF THE MELTING POINT<br />
axe provided, reactions in which gas or much heat is produced may<br />
not be performed in the shaking machine.<br />
DETERMINATION OF THE MELTING POINT<br />
The purity <strong>of</strong> a crystallised organic substance is checked by the<br />
melting point. This easily determined constant also serves for the<br />
identification <strong>of</strong> substances and, in the case <strong>of</strong> new compounds, for<br />
their characterisation. The apparatus is a long-necked, roundbottomed<br />
flask into which a tested thermometer is fixed by means<br />
<strong>of</strong> a cork ; a sector is cut out <strong>of</strong> the cork with a sharp knife in order<br />
that the whole <strong>of</strong> the thermometer scale may be visible (Fig. 31).<br />
The heating liquid is pure concentrated sulphuric<br />
acid, with which the bulb <strong>of</strong> the flask is threequarters<br />
filled. The substance, in powder form, is<br />
introduced into a small, thin-walled capillary tube.<br />
Such tubes are made as follows from test tubes<br />
(preferably from damaged tubes which must, however,<br />
be clean and dry!). The tubes are rotated<br />
in the flame <strong>of</strong> the blow-pipe till s<strong>of</strong>t and then<br />
drawn out rapidly; already after short practice<br />
the student can strike the correct diameter, which<br />
should be 1 -0-1 -5 mm. internally. Suitable portions<br />
<strong>of</strong> the drawn-out material are cut <strong>of</strong>f with scissors.<br />
It is convenient to cut double lengths (about 12<br />
cm.), so that by sealing each length in the middle<br />
(micro-burner) two melting-point tubes are obtained<br />
ready for use.<br />
FIG. 31<br />
A small amount <strong>of</strong> the thoroughly dried substance<br />
is powdered on a watch-glass or on a small piece <strong>of</strong> porous<br />
plate with a spatula or pestle, and a column <strong>of</strong> the powder about 2<br />
mm. long is formed at the bottom <strong>of</strong> the capillary tube by dipping<br />
the open end into it and tapping cautiously so as to shake the<br />
substance down from the mouth. If the substance sticks at any<br />
point above the bottom, the tube is allowed to fall several times<br />
through a long glass tube on to a glass plate or a watch-glass.<br />
Adherent substances can also be caused to slip down by scratching<br />
the tube gently with a file.<br />
The melting-point tube is then attached to the lower end <strong>of</strong> the<br />
thermometer in such a position that the substance is at the level <strong>of</strong>
SINTEKING 41<br />
the middle <strong>of</strong> the mercury bulb ; this is done most conveniently by<br />
transferring a drop <strong>of</strong> concentrated sulphuric acid from the bulb to<br />
the upper end <strong>of</strong> the capillary. The bulb itself must be completely<br />
immersed during the determination. The apparatus is now heated<br />
with a moderate-sized flame held obliquely and moved slowly and<br />
regularly round the bath, which must be illuminated by reflected<br />
light. Substances having high melting points can be heated rapidly<br />
at first, but in the neighbourhood <strong>of</strong> the melting point the temperature<br />
should be raised slowly. As a rule, at this stage small particles<br />
<strong>of</strong> substance adhering to the upper part <strong>of</strong> the tube are s<strong>of</strong>tened by<br />
the hotter ascending sulphuric acid, and further heating should be<br />
carried out cautiously. The melting point is reached when the<br />
specimen, having collapsed, forms a clear liquid. In the case <strong>of</strong><br />
substances <strong>of</strong> unknown melting point a preliminary determination<br />
is made.<br />
Many organic compounds do not melt without decomposition,<br />
which <strong>of</strong>ten shows itself by change <strong>of</strong> colour and usually by evolution<br />
<strong>of</strong> gas, which can be very distinctly observed in the capillary.<br />
Such substances do not possess sharp melting points, but have<br />
decomposition points which are almost always dependent on the<br />
rate <strong>of</strong> heating ; acceleration <strong>of</strong> the latter raises the decomposition<br />
point. The change produced by heat in these substances, below<br />
their point <strong>of</strong> decomposition, is also made evident by a shrinking and<br />
s<strong>of</strong>tening, which is called " sintering ".<br />
When the melting point <strong>of</strong> a decomposing substance is to be<br />
determined the bath is heated rather rapidly to within 10°-20° <strong>of</strong><br />
the temperature <strong>of</strong> decomposition, and from that point onwards the<br />
rate <strong>of</strong> heating is reduced to about 5° per minute.<br />
When stable substances sinter before melting it is a sign that<br />
they have not been completely purified, and should be recrystallised<br />
or redistilled. Some substances sinter, however, even when perfectly<br />
pure, i.e. they have no sharp melting point. In this connection the<br />
so-called " liquid crystals" may also be mentioned (Lehmann,<br />
Vorlander).<br />
The rule should be adopted that a substance is only regarded as<br />
pure when its melting point no longer changes on repetition <strong>of</strong> the<br />
process <strong>of</strong> purification.<br />
The reason why impurities lower the melting point is that they<br />
act to some extent as dissolved substances ; now it is well known<br />
that the freezing point <strong>of</strong> a solution is always lower than that <strong>of</strong> the
42 MELTING POINT OF MIXTURES<br />
solvent (cryoscopy). An important method <strong>of</strong> identification is based<br />
on this fact. When the melting point <strong>of</strong> a compound, obtained by<br />
a new method, suggests identity with a known substance a certain<br />
decision can be reached by determining the melting point <strong>of</strong> an<br />
intimate mixture <strong>of</strong> the two compounds. If A differs from B the<br />
two substances will behave towards each other as impurities and the<br />
melting point <strong>of</strong> the mixture will be lowered ; on the other hand, if<br />
they are identical the melting point will remain unchanged. It is<br />
convenient, when determining a " mixed melting point ", to test the<br />
three samples (A, B, and A+B) simultaneously on the same thermometer.<br />
With a little practice this can be done with one sample<br />
on each side and one in front, or, if the thermometer is thick enough,<br />
with all three alongside each other in front (at the same level!).<br />
In the single case <strong>of</strong> isomorphous substances the mixed meltingpoint<br />
test fails.<br />
There are also several methods for the determination <strong>of</strong> the<br />
boiling point, with small amounts <strong>of</strong> substance, in the melting-point<br />
apparatus.<br />
The use <strong>of</strong> the sulphuric acid bath above 250° is not without<br />
danger ; as soon as signs <strong>of</strong> boiling appear heating is stopped and<br />
even before that temperature is reached the possibility that the<br />
flask may crack must be taken into consideration. Higher temperatures<br />
(up to 350°) are attained by using a bath <strong>of</strong> sulphuric acid in<br />
which potassium sulphate has been dissolved by heat. This heating<br />
bath solidifies on cooling, because potassium hydrogen sulphate<br />
crystallises from it; it must therefore be just melted before the<br />
thermometer is introduced.<br />
Here only a general review <strong>of</strong> methods and manipulations has<br />
been given, in so far as they are employed in the preparative<br />
exercises. The comprehensive and thorough works <strong>of</strong> Lassar-Cohn,<br />
Hans Meyer, and Houben-Weyl should be consulted for special<br />
requirements.
B. ORGANIC ANALYTICAL METHODS<br />
DETECTION OF CARBON, HYDROGEN, NITROGEN, SULPHUR,<br />
AND THE HALOGENS<br />
Testing for Carbon and Hydrogen.—If a substance bums with a<br />
flame (exceptions, e.g. sulphur) or decomposes with separation <strong>of</strong><br />
black charcoal when heated on platinum foil, it is to be regarded as<br />
organic. The tests for carbon and hydrogen can be carried out<br />
simultaneously as follows : Mix a dry sample <strong>of</strong> the substance with<br />
several times its volume <strong>of</strong> fine ignited copper oxide in a small test<br />
tube and cover the mixture with a little more oxide. Stopper the<br />
test tube with a cork carrying a tube bent at right angles and heat<br />
strongly. If the gases evolved produce turbidity in clear baryta<br />
water (CO2), the substance contains carbon, while the appearance <strong>of</strong><br />
small drops <strong>of</strong> water in the upper part <strong>of</strong> the tube indicates the<br />
presence <strong>of</strong> hydrogen.<br />
Testing for Nitrogen.—Press a clean piece <strong>of</strong> potassium or sodium<br />
half the size <strong>of</strong> a lentil between filter paper, transfer it to a small<br />
test tube about 5 mm. wide and 6 cm. long, add a small sample <strong>of</strong><br />
the substance and heat in the flame <strong>of</strong> a Bunsen burner until decomposition<br />
occurs, usually accompanied by slight explosion and darkening.<br />
Then heat the tube to redness and dip it, while still hot, into<br />
a small beaker containing 5 c.c. <strong>of</strong> water. Uncombined metal may<br />
be ignited and the tube will crack (fume chamber!). Remove glass<br />
and carbon by filtering the solution, which contains cyanide if the<br />
substance contained nitrogen. Add two drops each <strong>of</strong> ferrous sulphate<br />
and ferric chloride solutions to the filtrate, make sure that it<br />
is alkaline by testing, and heat. If cyanide is present potassium<br />
ferrocyanide is formed in one to two minutes. Now cool and acidify<br />
the alkaline liquid with hydrochloric acid. The ferric and ferrous<br />
hydroxides which were precipitated go into solution and the potassium<br />
ferrocyanide reacts with the ferric chloride in the usual way,<br />
yielding Prussian blue. Hence if the substance contained nitrogen a<br />
43
44 DETECTION OF THE ELEMENTS<br />
blue precipitate separates. If the proportion <strong>of</strong> nitrogen in the substance<br />
is only small it occasionally happens that, at first, no precipitate<br />
is obtained, but only a bluish-green solution. If this is kept, for<br />
instance over night, a precipitate is deposited. When readily volatile<br />
substances are tested for nitrogen a longer tube is used and the<br />
material which condenses on the cold parts is allowed to flow back<br />
repeatedly on to the hot metal. Substances which lose their nitrogen<br />
already at moderate temperatures, e. g. diazo-compounds, cannot<br />
be tested in this way. When such substances are burned with<br />
copper oxide in a tube filled with carbon dioxide, a gas (nitrogen),<br />
which is not absorbed by potassium hydroxide solution, is produced<br />
(cf. quantitative determination <strong>of</strong> nitrogen).<br />
Testing for Sulphur.—The qualitative test for sulphur is carried<br />
out in the same way as that for nitrogen. Ignite the substance in a<br />
small tube with sodium, dissolve the product in water, and add to<br />
one half <strong>of</strong> the cooled solution a few drops <strong>of</strong> sodium nitroprusside<br />
solution freshly prepared by shaking a few particles <strong>of</strong> the solid salt<br />
with cold water. A violet colour indicates the presence <strong>of</strong> sulphur.<br />
Since the nitroprusside reaction is extremely sensitive and does not<br />
allow any estimate <strong>of</strong> the amount <strong>of</strong> sulphur to be made, filter the<br />
second half <strong>of</strong> the liquid, add lead acetate solution to the filtrate, and<br />
acidify with acetic acid. According as the amount <strong>of</strong> sulphur is<br />
small or large, a dark turbidity or a more or less heavy precipitate<br />
will form.<br />
Readily volatile compounds cannot, as a rule, be tested in this<br />
way. As described in the method for the quantitative determination<br />
<strong>of</strong> sulphur, they are heated in a sealed tube to about 200°-300°<br />
with fuming nitric acid, and the solution produced is diluted with<br />
water and tested for sulphuric acid with barium chloride.<br />
Testing for the Halogens.—Chlorine, bromine, and iodine can<br />
but rarely be detected in organic compounds by direct precipitation<br />
with silver nitrate, since the halogen usually does not form<br />
ions.<br />
In order to test for un-ionised halogen ignite the substance with<br />
an excess <strong>of</strong> chemically pure lime in a moderately wide test tube in a<br />
Bunsen flame, dip the tube while still hot in a little water so that the<br />
glass is shattered, acidify with pure nitric acid, filter, and add silver<br />
nitrate solution.<br />
In substances which contain no nitrogen the halogens can be<br />
detected by ignition with sodium as in the test for nitrogen. In this
BBILSTBIN'S TEST 45<br />
case remove glass and decomposition products by nitration, acidify<br />
the filtrate with pure nitric acid, and add silver nitrate solution.<br />
Halogen can be detected very rapidly and conveniently by<br />
Beilstein's test. Twist a platinum wire round a small piece <strong>of</strong><br />
copper oxide the size <strong>of</strong> a lentil or round a small rod <strong>of</strong> the oxide<br />
0-5 cm. long and heat in the Bunsen flame until the latter appears<br />
colourless. Now cool the oxide, place a minute portion <strong>of</strong> the substance<br />
containing halogen on it, and heat again in the outer part <strong>of</strong><br />
the flame. The carbon first burns with a luminous flame which<br />
soon disappears, leaving a green or blue-green region produced by<br />
the copper halide vapour. It is possible to deduce from the time<br />
during which the colour persists whether the substance contains only<br />
traces <strong>of</strong> halogen or more. The Beilstein test can also be made<br />
with a copper wire fixed in a cork.<br />
Other elements which occur in organic compounds, such as phosphorus,<br />
arsenic, other non-metals, and metals in organic combination,<br />
are detected by destroying the organic material by oxidation<br />
(with nitric acid in a sealed tube or by fusion with potassium nitrate<br />
or sodium peroxide) and then applying the usual tests.<br />
The determination <strong>of</strong> the elements which make up a substance<br />
is but a small part <strong>of</strong> its qualitative investigation. The next and<br />
more difficult task is to classify it, to show to what class <strong>of</strong> compounds<br />
it belongs in view <strong>of</strong> its chemical and physical properties and<br />
reactions. The ease with which it is possible to show that a polar<br />
compound is an acid or a base contrasts with the difficulties encountered<br />
in assigning a neutral substance <strong>of</strong> unknown constitution<br />
to the correct class. The recognition <strong>of</strong> the characters <strong>of</strong> the most<br />
important organic groups (<strong>of</strong> alcohols, aldehydes, ketones, esters,<br />
amides, nitriles and nitro-compounds, to mention a few only), the<br />
differentiation <strong>of</strong> saturated, unsaturated, and aromatic substances<br />
by their reactions—the experimental solution <strong>of</strong> these and many<br />
other questions constitute an indispensable secondary object <strong>of</strong> a<br />
course <strong>of</strong> preparative organic chemistry. The student should not<br />
only acquire practice in the synthesis <strong>of</strong> representative compounds ;<br />
he should also become conversant with the properties <strong>of</strong> the substances<br />
he prepares, he should become thoroughly acquainted with<br />
their characteristic reactions, and by close scrutiny and experimental<br />
observation he should fix their individuality in his mind.<br />
Hence the illustrative experiments included in the following course
46 ORGANIC ELEMENTARY ANALYSIS<br />
<strong>of</strong> preparative work are intended to further the educational object above<br />
indicated, and should be taken seriously. The carrying out <strong>of</strong> these<br />
reactions should be considered just as important as the purely preparative<br />
work.<br />
In the course <strong>of</strong> the scientific work which succeeds the preparative<br />
course, and indeed whenever the chemist has to deal independently<br />
with a problem, questions requiring a knowledge <strong>of</strong><br />
qualitative analysis continually arise. Because <strong>of</strong> the limited time<br />
available we have unfortunately hitherto not attained the ideal <strong>of</strong><br />
following up the preparative work with a comprehensive course<br />
in the qualitative identification <strong>of</strong> organic substances, but nevertheless<br />
the closest attention should be given to this branch <strong>of</strong> study.<br />
General aids to the study here outlined should be sought during<br />
the practical course in Hans Meyer's thorough work, Analyse<br />
und Konstitutionsermittlung organischer Verbindungen. Formal<br />
schemes <strong>of</strong> analysis, leading to the classification <strong>of</strong> organic substances,<br />
have also been worked out, e.g. by H. Staudinger in his<br />
Anleitung zur organischen qualitativen Analyse, 2 Aufl., Berlin, 1929.<br />
ORGANIC ELEMENTARY ANALYSIS<br />
The quantatitive determination <strong>of</strong> the elements in an organic<br />
substance is known as elementary analysis. In this process carbon<br />
and hydrogen are determined simultaneously, whilst a separate<br />
analysis must be carried out for the determination <strong>of</strong> each <strong>of</strong> the<br />
other elements.<br />
The meso-analytical methods here described are carried out with<br />
20-30 mg. <strong>of</strong> material. They have been worked out on the basis <strong>of</strong><br />
Pregl's micro-procedure by Dr. F. Holscher. 1 For almost two years<br />
they have been in use in the Munich laboratories and have proved<br />
to be excellent: they have displaced the macro-analytical methods<br />
completely here.<br />
The Balance.—For reasons which can easily be perceived an<br />
ordinary analytical balance, accurate to within only 0-1 nig. cannot<br />
be used for weighing 20-30 mg. <strong>of</strong> substance. Accordingly a<br />
modern analytical balance (pointer reading method), a Kuhlmann<br />
1 F. Pregl and H. Roth, Die quantitative organ. Mikroanalyse (Springer, Berlin,<br />
1935); cf. H. Berger, J. pr. Chem., 1932, 133, 1 ; K. Kuspert, Chem. Fabr., 1933,<br />
6, 63; E. Sucharda and B. Bobrahski, Semimicro-<strong>Methods</strong> for the Elementary<br />
Analysis <strong>of</strong> <strong><strong>Org</strong>anic</strong> Compounds (London, 1936, A. Gallenkamp).
DETEKMINATION OF NITKOGEN 47<br />
rapid-weighing balance, or a similar " half-micro " balance with a<br />
limit <strong>of</strong> accuracy <strong>of</strong> 0-01 mg. is used. 1<br />
I. DETERMINATION OF NITROGEN BY DUMAS' METHOD<br />
A weighed quantity <strong>of</strong> substance is ignited with copper oxide in<br />
an atmosphere <strong>of</strong> carbon dioxide. The carbon is thus oxidised to<br />
carbon dioxide and the hydrogen to water, whilst the nitrogen is<br />
liberated as such and is determined volumetrically after collection<br />
over potassium hydroxide solution. Any oxides <strong>of</strong> nitrogen which<br />
may be formed are reduced to nitrogen by means <strong>of</strong> a glowing copper<br />
spiral. For the determination <strong>of</strong> nitrogen the following are required<br />
:<br />
A combustion tube <strong>of</strong> heat-resistant glass having a constriction at<br />
one end (length, without the constricted part 55 cm., external<br />
diameter 12 mm., length <strong>of</strong> the constricted part 3 cm., external<br />
diameter 3-3-5 mm., internal diameter 2 mm.).<br />
A one-holed rubber stopper. This stopper should be as nearly<br />
cylindrical as possible, should fit the wider opening <strong>of</strong> the tube,<br />
and must sit close to the wall <strong>of</strong> the tube.<br />
Wire-form copper oxide (" for analysis ").<br />
Long-fibre asbestos wool.<br />
Some silver wool.<br />
Two asbestos plates and a roll <strong>of</strong> iron-wire gauze (length 5 cm.;.<br />
Kipp apparatus, electric combustion furnace, 2 nitrometer, nickel<br />
dish, sieve <strong>of</strong> wire gauze, weighing bottle, and mixing tube are<br />
supplied by the laboratory.<br />
PREPARING THE APPARATUS<br />
Air-free Kipp fox Carbon Dioxide.—Cover small pieces <strong>of</strong> marble in<br />
a porcelain basin with dilute hydrochloric acid (1 vol. <strong>of</strong> HC1, d. 1-18 +<br />
1 vol. <strong>of</strong> water). After the first vigorous reaction has subsided pour<br />
<strong>of</strong>f the scum which collects on the surface and wash the chips with water.<br />
Now more than half-fill the middle globe <strong>of</strong> the Kipp with the chips, the<br />
opening from the lower globe being packed with chips <strong>of</strong> glass or closed<br />
with two semicircular glass rods. When the gas is being delivered<br />
from the apparatus it is taken from the highest point in the middle<br />
1 Details <strong>of</strong> the technique <strong>of</strong> weighing will be found in the Introduction by F.<br />
Holscher, Munich, 1934, State Chemical <strong>Laboratory</strong>. This book is privately<br />
published.<br />
a A suitable furnace is supplied by Griffin and Tatlock, London. The tube has<br />
two'supports, nob one as in Fig. 32. The resistance is mounted on the base-plate.
48 THE DUMAS METHOD<br />
globe through a glass tube shaped like a hook with the point upwards.<br />
This tube is attached by means <strong>of</strong> a short piece <strong>of</strong> rubber tubing to the<br />
inner end <strong>of</strong> the tube carrying a glass stop-cock which is fitted into the<br />
side opening <strong>of</strong> the globe. A rubber stopper, greased with a little<br />
vaseline, holds the stop-cock in place in this opening. Now pour dilute<br />
hydrochloric acid into the apparatus until the lowest globe and half <strong>of</strong><br />
the uppermost globe are filled (as in Fig. 32) and drop two small pieces<br />
FIG. 32<br />
<strong>of</strong> marble into the stem <strong>of</strong> the funnel globe so that they are trapped and<br />
remove the air dissolved in the acid by producing a vigorous evolution<br />
<strong>of</strong> carbon dioxide. Accelerate this removal by opening and closing<br />
the cock repeatedly.<br />
As a rule a newly charged Kipp supplies sufficiently pure carbon<br />
dioxide only after two or three days' standing. This time is required for<br />
the air adsorbed on the surface <strong>of</strong> the glass and rubber to be given up<br />
to the carbon dioxide atmosphere. When the " micro-bubbles " rising<br />
in the nitrometer, <strong>of</strong>ten overtaking each other and combining—when<br />
these bubbles ascend at a uniform rate, the gas may be regarded as<br />
satisfactory. The diameter <strong>of</strong> the bubbles (examined with a lens)<br />
should not exceed one-fifth <strong>of</strong> the distance between two graduation<br />
marks (about 0-2 mm.).<br />
The Kipp is attached to the combustion tube by means <strong>of</strong> a Z-shaped<br />
glass tube one end <strong>of</strong> which is drawn out to form a thick-walled, roughly<br />
conical capillary. This is pushed through the hole in the rubber stopper<br />
fixed in the combustion tube. At the other end is attached a short<br />
glass tube filled with asbestos wool to trap acid fog. This tube fits over<br />
the horizontal delivery tube from the stop-cock <strong>of</strong> the Kipp, the wellfitting<br />
glass-to-glass joint being made as tight as possible by means <strong>of</strong> a<br />
piece <strong>of</strong> rubber tubing moistened with a little glycerol (see Fig. 32).'
FILLING THE COMBUSTION TUBE 49<br />
Filling the Combustion Tube.—First clean the combustion tube<br />
with bichromate-sulphuric acid mixture, wash with distilled water,<br />
and dry with gentle warming, drawing a current <strong>of</strong> air through by<br />
means <strong>of</strong> a water-jet pump. Keep a stock <strong>of</strong> coarse wire-form<br />
copper oxide (" for analysis ") and <strong>of</strong> more finely broken copper<br />
oxide prepared from the coarse quality by powdering (not grinding)<br />
in a mortar so that, after dust has been removed with a sieve, the<br />
pieces are 1-2 mm. long. Ignite the copper oxide in a nickel basin<br />
before use. Used copper oxide is ready for immediate re-use after<br />
it has been sieved and heated to redness in air.<br />
Care must be taken to avoid contamination <strong>of</strong> the copper oxide<br />
with, alkaline solutions since such contamination results in nitrogen<br />
values which, are always too low. The only remedy, should contamination<br />
occur, is to boil with, acetic acid and re-ignite.<br />
First fill the conical part <strong>of</strong> the tube with some silver wool.<br />
Then push in some purified and ignited asbestos wool up to the<br />
constriction, using a suitable glass rod smoothly rounded at the end<br />
and pressing moderately hard, so that a pad 2-3 mm. thick is produced.<br />
After the asbestos pour in a column <strong>of</strong> coarse copper oxide<br />
12 cm. long, holding the tube vertically and striking it with the<br />
palm <strong>of</strong> the hand so that a moderately compact column is formed.<br />
In the same way, pour in now a 6 cm. column <strong>of</strong> the finely broken<br />
copper oxide and, after that, a 10 cm. column <strong>of</strong> the coarse. Confine<br />
this " permanent filling " in the tube by means <strong>of</strong> a second asbestos<br />
pad, gently pressed and a few millimetres thick.<br />
Now pass into the filled tube, from the wide end, a current <strong>of</strong><br />
hydrogen (washed with acid permanganate solution), reduce the<br />
6 cm. column <strong>of</strong> finely broken copper oxide by heating at a moderately<br />
high temperature with a Bunsen burner after completely<br />
expelling the air, and allow to cool slowly in a current <strong>of</strong> hydrogen.<br />
Then burn out the whole length <strong>of</strong> the newly prepared tube with its<br />
" permanent filling " in the electric furnace at a high temperature<br />
and leave to cool while filled with carbon dioxide at the pressure <strong>of</strong><br />
the Kipp. Always keep the tube when not in use connected to the<br />
Kipp and full <strong>of</strong> carbon dioxide at this pressure.<br />
The Half-micro-nitrometer.—The half-micro-nitrometer used to<br />
collect the nitrogen has a capacity <strong>of</strong> 8—10 c.c, a volume which corresponds<br />
to 20-30 mg. <strong>of</strong> substance. A completely satisfactory degree <strong>of</strong><br />
accuracy in measuring the gas is attained by graduating in sub-divisions<br />
<strong>of</strong> 0-02 c.c.
50 THE DUMAS METHOD<br />
The gas inlet tube <strong>of</strong> the nitrometer carries a fused-in glass stop-cock<br />
having a tap with a long arm. In order further to increase the degree<br />
<strong>of</strong> fine adjustment two fine grooves pointed at the outer ends are cut in<br />
the barrel <strong>of</strong> the tap (Fig. 33) by means <strong>of</strong> a sharp triangular<br />
file. The positions <strong>of</strong> these grooves are such<br />
that the long arm must be turned upwards in order to<br />
allow the gas to pass. The gas inlet tube <strong>of</strong> the nitrometer<br />
is connected to the combustion tube by means <strong>of</strong><br />
an obtuse-angled capillary tube and a piece <strong>of</strong> thickwalled<br />
rubber tubing covering the well-fitting glass-toglass<br />
joint. The external diameter <strong>of</strong> the capillary<br />
tube at the joint exactly corresponds with that <strong>of</strong> the<br />
tube from the stop-cock. The horizontal arm <strong>of</strong> the<br />
FIG. 33 capillary tube is drawn out to a roughly conical tip<br />
having external diameter exactly the same as that <strong>of</strong><br />
the constricted part <strong>of</strong> the combustion tube. A piece <strong>of</strong> narrowbored<br />
pressure tubing, 2-5-3 cm. long, moistened with a little glycerol,<br />
serves to cover the carefully fitted glass-to-glass joint between combustion<br />
tube and capillary tube. When the apparatus is taken<br />
apart the capillary tube is always left attached to the nitrometer.<br />
Before it is filled the nitrometer is cleaned with bichromate-sulphuric<br />
acid mixture. The rubber tube connecting the levelling bulb and the<br />
nitrometer is made fast with wire binding. Pure mercury is run in<br />
from the bulb until the level is 1-2 mm. above the highest point <strong>of</strong> the<br />
orifice <strong>of</strong> the inlet tube. The stop-cocks are greased slightly with<br />
vaseline, the grooves being kept clear. The liquid for filling the nitrometer<br />
is 50 per cent potassium hydroxide solution (from pure " stick<br />
potash ") which has been made completely free from froth by shaking<br />
with finely powdered baryta (2 g. per 200 g. <strong>of</strong> solution) and filtering<br />
through a dry filter.<br />
The levelling bulb is closed with a rubber stopper carrying a short<br />
glass tube drawn out to a capillary.<br />
Preparing the Substance.—Burn solid substances either after drying<br />
in air or immediately after drying to constant weight in an evacuated<br />
desiccator over sulphuric acid. It is not advisable first to powder the<br />
substance finely and so to increase its surface area unnecessarily. Such<br />
procedure adds greatly to the difficulty <strong>of</strong> weighing hygroscopic substances.<br />
If the substance retains some <strong>of</strong> the solvent dry at an increased<br />
temperature in a vacuum in a so-called drying pistol or, more<br />
conveniently, in a copper block desiccator (Pregl) which can easily be<br />
finely adjusted to any desired temperature by regulating the micr<strong>of</strong>lame<br />
which heats the block (Fig. 34). Weigh hygroscopic substances<br />
in a small weighing tube.
THE DUMAS METHOD 51<br />
FIG. 34<br />
CARRYING OUT THE COMBUSTION<br />
Weighing.—Weigh solid substances in a small pear-shaped tube<br />
having a ground-in stopper. This tube serves also as a mixing tube,<br />
and its diameter is so chosen that it can be conveniently inserted a<br />
few centimetres into the cylindrical funnel attached to the combustion<br />
tube. Clean the weighing tube with a pad <strong>of</strong> cotton wool<br />
wrapped round a thin wire, pour in a little <strong>of</strong> the fine copper oxide<br />
and weigh to 0-01 mg. on the balance. Always use forceps when<br />
handling the weighing tube. Now place the tube upright on a<br />
suitable wire stand, pour in 20-30 mg. <strong>of</strong> substance with a thin<br />
nickel spatula and re-weigh.<br />
Weigh liquids in a glass capillary tube 2 mm. in diameter and 7 to<br />
8 cm. long cut with a sharp glass-knife from a drawn-out test tube. First<br />
close the tube (Fig. 35) in the middle by fusing the glass over a very small<br />
Bunsen flame made just non-luminous,<br />
rotating the tube slowly and pressing<br />
the ends very gently inwards so that<br />
a solid lump <strong>of</strong> glass is formed in the<br />
middle. Then remove from the flame<br />
and draw out so as to produce a rod<br />
about 2-5 cm. long. Snap in the middle<br />
with the finger-nail and so obtain two<br />
capillary tubes with solid handles. Now<br />
drop a small crystal <strong>of</strong> potassium chlor-<br />
^ -<br />
ate to the bottom <strong>of</strong> the capillary tube,<br />
FlQ - 35<br />
melt cautiously over the micro-flame,<br />
and allow to cool. After introducing two minute granules <strong>of</strong> purified<br />
pumice s<strong>of</strong>ten the tube about 1 cm. from the bottom, rotating quite<br />
uniformly and slowly, remove from the flame, draw out to a fine capillary<br />
about 2 cm. long, and break <strong>of</strong>f. Now wipe the capillary first with a moist<br />
flannel cloth and then with a clean dry piece <strong>of</strong> linen, allow to cool completely,<br />
and weigh accurately to 0 -01 mg. Next cautiously warm the wide
52 THE DUMAS METHOD<br />
part <strong>of</strong> the weighed capillary over the micro-flame without melting the<br />
potassium chlorate, and dip into the liquid. After a suitable amount <strong>of</strong><br />
liquid has been sucked in, grasp the tube by the handle and shake the<br />
part <strong>of</strong> the liquid remaining in the capillary down to the bottom by holding<br />
the tube upright and striking it gently with the hand or by shaking<br />
suitably. In order completely to remove liquid from the fine capillary pass<br />
it rapidly a few times through the outer envelope <strong>of</strong> the flame, wipe it,<br />
make sure that no charring has occurred, and then seal the tip <strong>of</strong> the<br />
capillary; wipe with a moist flannel cloth, then with a clean linen cloth,<br />
and after allowing to cool for a few minutes accurately determine the<br />
increase in weight to 0 - 0l mg. Fill the combustion tube exactly as<br />
usual for nitrogen determination but use a 2-3 cm. column <strong>of</strong> fine copper<br />
oxide instead <strong>of</strong> 0-5 cm., shorten the weighed capillary tube by breaking<br />
<strong>of</strong>f the tip and the handle, cover with a small roll (4 cm. long) <strong>of</strong> freshly<br />
ignited oxidised copper wire gauze, and slip both, the capillary with its<br />
tip foremost, into the combustion tube held in a sloping position.<br />
Finally, fill up with copper oxide as usual.<br />
Filling the Combustion Tube and Setting Up the Apparatus.—<br />
Make a funnel from a wide test-tube and attach it to the combustion<br />
tube. Pour in first 7 cm. <strong>of</strong> coarse and then 0-5 cm. <strong>of</strong><br />
fine copper oxide, holding the tube upright and forming a moderately<br />
compact column by striking the side with the hand. Now cover<br />
the substance in the weighing tube with a layer, 2 cm. deep, <strong>of</strong> fine<br />
copper oxide, insert the stopper, shake well and empty the contents<br />
into the combustion tube. In the same way wash out the weighing<br />
tube three or four times with 1-1-5 cm. layers <strong>of</strong> fine copper oxide,<br />
tap the tube so that the fine particles also slip into the combustion<br />
tube, and finally pour in 4-5 cm. more <strong>of</strong> coarse copper oxide. Then<br />
place the tube in the electric furnace, so that, at the constricted end,<br />
2 cm. <strong>of</strong> the copper oxide filling projec't from the furnace ; for protection<br />
against heat slip a small asbestos screen over the constricted end<br />
and against the end <strong>of</strong> the furnace. Over the other end slip a roll<br />
5 cm. long <strong>of</strong> iron-wire gauze and a small asbestos screen to protect<br />
the rubber stopper from heat. Switch on the current, close the wide<br />
end <strong>of</strong> the tube with a one-holed rubber stopper, moisten the hole<br />
with a little glycerol, insert the capillary <strong>of</strong> the tube connecting<br />
with the Kipp so that the capillary projects just beyond the stopper,<br />
and open the stop-cock on the Kipp. Pass carbon dioxide through<br />
the tube for a few minutes and then connect the constricted end with<br />
the nitrometer, its stop-cock being open and the potassium hydroxide<br />
solution being transferred as completely as possible to the levelling
THE DUMAS METHOD 53<br />
bulb lowered for the purpose. After two more minutes, when the<br />
connecting tube and stop-cock have been washed out with the gas,<br />
close the stop-cock, fill the nitrometer, lower the levelling bulb again,<br />
cautiously open the stop-cock so that one to two bubbles per second<br />
pass through, and observe the size <strong>of</strong> the micro-bubbles which<br />
remain. If these are not yet small enough repeat the washing out<br />
with carbon dioxide. As soon as sufficiently small bubbles are<br />
produced close the Kipp and fully open the stop-cock on the connecting<br />
tube. At the same time push the roll <strong>of</strong> wire gauze over<br />
the last portion <strong>of</strong> copper oxide filling and place the moveable<br />
Bunsen burner underneath so that the part <strong>of</strong> the tube protected<br />
by the roll is in the flame, which is turned full up and made nonluminous.<br />
The Combustion.—As soon as the electric furnace begins to glow<br />
—15-20 minutes after switching on—and the evolution <strong>of</strong> gas<br />
caused by the heating <strong>of</strong> the tube with the Bunsen burner has<br />
ceased, close the stop-cock on the connecting tube, hold the levelling<br />
bulb just above the level <strong>of</strong> the stop-cock at the top <strong>of</strong> the nitrometer,<br />
and drive all the gas which has collected as well as accompanying<br />
impurities into the upper part (above the stop-cock) <strong>of</strong> the<br />
nitrometer by turning the tap rapidly on and <strong>of</strong>f allowing a little<br />
<strong>of</strong> the solution to pass above the stop-cock. Now lower the levelling<br />
bulb again, open full the stop-cock on the connecting tube and push<br />
the roll <strong>of</strong> wire gauze forward a few millimetres so that the Bunsen<br />
flame impinges on the rear end. In the same way move the roll<br />
and the burner or the electric heater forward as long as the rate at<br />
which the bubbles appear remains less than the permitted : take<br />
great care that the bubbles enter the nitrometer at a rate never<br />
exceeding two bubbles in three seconds. Consequently, when the<br />
evolution <strong>of</strong> gas is vigorous, and particularly when the substance<br />
has been reached, wait rather longer and continue the movement<br />
only after the rate <strong>of</strong> appearance <strong>of</strong> bubbles has considerably<br />
diminished. As soon as the Bunsen burner has been moved as far<br />
as the electric furnace (fifteen to twenty minutes are required for this)<br />
close the cock on the connecting tube, open full that on the Kipp<br />
apparatus, and then, by cautious movement <strong>of</strong> the fine adjustment<br />
arm <strong>of</strong> the stop-cock on the connecting tube, admit gas to pass into<br />
the nitrometer at the rate <strong>of</strong> two bubbles every three seconds. Carefully<br />
avoid exceeding this rate even for a short time. Now strongly<br />
heat the part <strong>of</strong> the copper oxide which is removed for each com-
54 THE DUMAS METHOD<br />
bustion for five to ten minutes longer, moving the burner and the roll<br />
as required. After that remove the burner and, five minutes later<br />
switch <strong>of</strong>f the current in the furnace. Avoid heating the combustion<br />
tube with the burner alone for long periods since such treatment<br />
causes the glass to s<strong>of</strong>ten and infallibly to blow out. When heating<br />
has been stopped increase the rate <strong>of</strong> passage <strong>of</strong> gas to two bubbles<br />
per second.<br />
As soon as micro-bubbles only are being produced in the nitrometer<br />
close the stop-cock on the connecting tube, detach the rubber<br />
connecting tube from the combustion tube, close the latter with a<br />
cap made from rubber tubing, and leave to cool whilst maintaining<br />
the internal carbon dioxide pressure. Remove the nitrometer to a<br />
somewhat cooler room (room in which the barometer is kept preferably)<br />
after raising the bulb so that the surfaces <strong>of</strong> the two columns<br />
<strong>of</strong> liquid are at the same level.<br />
After ten minutes take the reading by holding the bulb behind<br />
the graduated tube with the meniscus in the bulb accurately in the<br />
same plane as the meniscus in the tube. Read the scale division<br />
which is in the same horizontal plane as the lower edge <strong>of</strong> the<br />
meniscus. Also note the temperature (thermometer in the part <strong>of</strong><br />
the nitrometer above the stop-cock) and the barometric pressure.<br />
Calculation.—The percentage <strong>of</strong> nitrogen is given by the following<br />
formula :<br />
in which v is the volume <strong>of</strong> nitrogen read, a = ^=0-003663,<br />
2i to<br />
b is the barometric height, S is the correction <strong>of</strong> the barometric<br />
height to 0°, e is the vapour pressure <strong>of</strong> potassium hydroxide at t 0 , 1<br />
and s is the amount <strong>of</strong> substance taken.<br />
Limits <strong>of</strong> error <strong>of</strong> the determination : 0-3 per cent high, 0-1 per<br />
cent low.<br />
1 The values <strong>of</strong> the expression between brackets are given for various values <strong>of</strong><br />
b— 8 — e and t in the table on pp. 424, 425. With sufficient accuracy S may be replaced<br />
by Q and e by •=. For example : readings, 6 = 738 mm., t = 20° ; look up in<br />
the table the value for p =738- 2-5- 4 = 731-5. When calculating logarithmically<br />
use Kuster"s tables.
DETEKMINATION OF CAKBON AND HYDEOGBN 55<br />
II. DETERMINATION OF CARBON AND HYDROGEN BY<br />
LIEBIG'S METHOD<br />
The method is essentially as follows : A weighed amount <strong>of</strong><br />
substance is oxidised in a combustion tube in a current <strong>of</strong> air or<br />
oxygen by means <strong>of</strong> platinum catalyst or copper oxide and lead<br />
chromate and the oxidation products are absorbed, carbon dioxide<br />
by sodium hydroxide, water by calcium chloride, and are weighed.<br />
By using a " universal filling " all substances can be analysed in the<br />
same tube no matter whether they contain, in addition to carbon<br />
and hydrogen, nitrogen, halogen, or sulphur. Any oxides <strong>of</strong><br />
nitrogen produced are reduced to nitrogen by means <strong>of</strong> a layer <strong>of</strong><br />
glowing copper, halogen is trapped by silver wool and sulphur by<br />
lead chromate and silver wool.<br />
The apparatus required for determination <strong>of</strong> C and H is as<br />
follows:<br />
FIG. 36<br />
A combustion tube with, constriction (as in N determination).<br />
A one-holed rubber stopper which fits well and sits close to the wall<br />
<strong>of</strong> the tube.<br />
A calcium chloride absorption tube.<br />
A sodium hydroxide-asbestos absorption tube.<br />
Two pieces <strong>of</strong> narrow-bored pressure tubing 1-5 to 2 cm. in length.<br />
These are to be impregnated with vaseline in a vaccuum (cf. p. 57).<br />
A piece <strong>of</strong> silver wire, length 8-10 cm., diameter 1 mm.<br />
1 -0 g. <strong>of</strong> silver wool.<br />
Purified asbestos wool (" Gooch crucible asbestos for analysis ").<br />
Coarse and fine copper oxide.<br />
Copper oxide with lead chromate (cf. p. 59).<br />
Sodium hydroxide-asbestos (Merck's " for analysis ").<br />
Cotton wool, ordinary and dried at 100°.<br />
The platinum articles and the rest <strong>of</strong> the apparatus are supplied by<br />
the laboratory.
56 FILLING THE OXYGEN GAS-HOLDEE<br />
PREPARING THE APPARATUS<br />
Filling the Oxygen Gas-holder.—Open the cocks a and b (Fig. 37)<br />
and so fill the lower container completely with water. Now close both<br />
cocks, unscrew the cap c, introduce a rubber<br />
tube connected with an oxygen cylinder<br />
through the opening c and fill the holder with<br />
oxygen. Screw on the cap and fill the upper<br />
container with water. When the cocks a and<br />
-»5E 3 b are opened oxygen flows out at b.<br />
No further description <strong>of</strong> the filling <strong>of</strong> the<br />
holder with air is required.<br />
The Pressure Regulator.—The object <strong>of</strong><br />
this important piece <strong>of</strong> apparatus is to maintain<br />
a constant rate <strong>of</strong> passage <strong>of</strong> the gas<br />
current during the combustion. Its mode <strong>of</strong><br />
action can be seen in the diagram (cf. Fig. 36).<br />
Essentially it consists <strong>of</strong> a gas wash-bottle<br />
FIG. 37 half-filled with water containing some sodium<br />
hydroxide. The inlet tube can be adjusted<br />
in a cork ring fixture so as to give any desired pressure up to 15<br />
cm. <strong>of</strong> water. The gas wash-bottles <strong>of</strong> the regulators are connected<br />
to the storage gas holder by means <strong>of</strong> long rubber tubes which, in common<br />
with all rubber tubing connexions from gas-holder to combustion<br />
tube, are " artificially aged" for safety's sake in order to avoid combustible<br />
constituents being given up to the gas current by the fresh rubber<br />
tubing.<br />
New tubing is artificially aged by heating in the drying oven at<br />
100-110° (not higher !) drawing air through at the same time for one<br />
hour by means <strong>of</strong> a water jet pump.<br />
The connecting tubes are fitted with accurately adjustable clips with<br />
which the current from the storage gas-holder is so regulated that<br />
successive bubbles escape from the gas wash-bottles at the longest<br />
possible intervals (say every ten to fifteen seconds). The delivery tubes<br />
from the gas wash-bottles are connected by means <strong>of</strong> artificially aged<br />
tubing with the arms <strong>of</strong> a three-way stop-cock which permits convenient<br />
switching over from one gas current to the other. In order to maintain<br />
the concentration <strong>of</strong> the potassium hydroxide solution in the bubble<br />
counter on the outlet from the three-way cock a small calcium chloride<br />
tube containing coarse calcium chloride is interposed between gas washbottles<br />
and three-way cock.<br />
The Bubble-Counter and Drying Apparatus.—The bubble-counter<br />
is sealed on to the drying apparatus, which consists <strong>of</strong> a U-tube with two<br />
ground glass stoppers filled with sodium hydroxide-asbestos and calcium<br />
chloride.<br />
The apparatus is cleaned, dried, and filled as follows. A large pad <strong>of</strong>
THE DEYING APPAEATUS 57<br />
cotton wool is pushed through the opening adjacent to the bubblecounter<br />
almost to the lowest point in the bend, the tube leading to the<br />
bubble-counter is temporarily closed with a roll <strong>of</strong> cotton wool pushed<br />
in with a steel wire and a layer 0 - 5 cm. deep <strong>of</strong> ordinary not specially<br />
dried calcium chloride is introduced with tapping. This layer is fixed in<br />
position with a small pad <strong>of</strong> cotton wool and sodium hydroxide-asbestos<br />
(Merck's " for analysis ") is then poured in until the tube is filled almost<br />
to the level <strong>of</strong> the side tube. After this layer also has been fixed in<br />
position by means <strong>of</strong> pad <strong>of</strong> cotton wool, the roll in the side tube is<br />
replaced by a loosely fitting plug <strong>of</strong> cotton wool, ordinary coarse calcium<br />
chloride is poured in up to the level <strong>of</strong> the stopper, another pad <strong>of</strong><br />
cotton wool is pushed in and the stopper, which is smeared with just<br />
sufficient vaseline to make it appear transparent, is inserted. The<br />
bubble-counter is now filled with 50 per cent potassium hydroxide<br />
solution (non-frothing) by means <strong>of</strong> a drawn-out glass tube pushed into<br />
the free side tube. The solution just covers the tip <strong>of</strong> the small inlet<br />
tube. The inside and also the outside <strong>of</strong> the side tube are carefully<br />
cleaned with a roll <strong>of</strong> cotton wool. A loosely fitting roll <strong>of</strong> dried cotton<br />
wool is now inserted into the other side tube through the other opening<br />
<strong>of</strong> the U-tube, this side tube is closed with a rubber cap and calcium<br />
chloride is poured in with tapping up to the level <strong>of</strong> the stopper. The<br />
calcium chloride is in granules <strong>of</strong> the size <strong>of</strong> lentils and is first dried in'<br />
the oven at 18O°-2OO°. After this layer <strong>of</strong> calcium chloride has been<br />
fixed in position with a dried cotton wool pad the stopper is made gastight<br />
with vaseline. Then the bubble-counter is connected to the<br />
three-way stop-cock by means <strong>of</strong> an artificially aged rubber tube 25 cm.<br />
long. The whole drying apparatus, suspended on a freely moving wire<br />
stirrup, is attached to a stand.<br />
Great care must be taken that, when no gas is passing through the<br />
drying apparatus, its side tube, which leads to the combustion tube,<br />
remains closed by means <strong>of</strong> a rubber cap in order to protect the calcium<br />
chloride from atmospheric moisture. When the calcium chloride at the<br />
outlet is exhausted—the sodium hydroxide-asbestos lasts much longer—<br />
the stopper is removed and about half <strong>of</strong> the column is replaced with<br />
fresh calcium chloride.<br />
The drying apparatus is connected to the combustion tube by means<br />
<strong>of</strong> a glass jet made from a capillary tube having the same external<br />
diameter as the side tube <strong>of</strong> the drying apparatus. This capillary is<br />
drawn out so that it forms an elongated cone which is connected to the<br />
side tube by means <strong>of</strong> a piece <strong>of</strong> pressure tubing impregnated in a vacuum<br />
with molten vaseline and remains always attached to drying apparatus.<br />
When this apparatus is not in use the glass jet is always kept closed by<br />
means <strong>of</strong> a cap made from narrow-bored pressure tubing.<br />
The rubber connexions for the drying apparatus and the small<br />
absorption tube are impregnated with vaseline in a vacuum by suspending<br />
a series <strong>of</strong> small pieces <strong>of</strong> narrow-bored pressure tubing 1 -5 and
58 FILLING THE COMBUSTION TUBE<br />
2 cm. long on a string, completely submerging them in a round flask<br />
two-thirds filled with molten vaseline, closing the flask with a rubber<br />
stopper which clamps the ends <strong>of</strong> the string against the neck <strong>of</strong> the flask<br />
and evacuating at the temperature <strong>of</strong> the water bath by means <strong>of</strong> a<br />
water-jet pump. At first the occluded gases escape with copious<br />
frothing. The pressure is occasionally restored for a short time and the<br />
flask again evacuated until only isolated bubbles appear. The heating<br />
is continued for not more than half an hour as otherwise the rubber<br />
swells. When the tubing has been allowed to drain and has been wiped<br />
clean outside and inside it is ready for use. On connecting with the<br />
combustion tube the jet is inserted so far into the rubber stopper that<br />
the tip just projects. In order to prevent the glass from adhering to<br />
the stopper both are moistened with a trace <strong>of</strong> glycerol, excess being<br />
removed by careful wiping with cotton wool.<br />
Filling the Combustion Tube.—Twist one end <strong>of</strong> a silver wire<br />
(diameter 1 mm.) into a flat spiral and push it, the other end first,<br />
into the cleaned and dried tube so that it remains fast with the end<br />
just projecting from the constriction. Being a good conductor <strong>of</strong><br />
heat this wire prevents condensation <strong>of</strong> water in the constricted<br />
part <strong>of</strong> the tube. Now push up to the constriction with a rounded<br />
glass rod <strong>of</strong> suitable size a pad <strong>of</strong> silver wool and press it fairly tight<br />
so that it forms a layer 0-7 cm. long. Next push in a small pad <strong>of</strong><br />
freshly ignited asbestos wool (for Gooch crucible) pressing it gently<br />
against the silver wool so that it forms a layer 2 mm. thick. Pour<br />
in fine copper oxide to form a 1-5 cm. layer and above it place an<br />
asbestos pad similar to the first. Then pour in a layer, 5 cm. thick,<br />
<strong>of</strong> fine copper oxide, which is reduced in a current <strong>of</strong> hydrogen<br />
when the tube has been filled (see below). Hold the tube vertically<br />
and strike the sides with the palm <strong>of</strong> the hand so that the copper<br />
oxide settles well. Fix in position with a small asbestos pad.<br />
At this part <strong>of</strong> the tube introduce a pad, 7 cm. long, <strong>of</strong> longfibre<br />
ignited asbestos, by pushing in three separate portions <strong>of</strong> the<br />
material and pressing each time quite gently with the glass rod<br />
(avoid excessive pressure). This pad acts as a brake which "prevents<br />
a sudden change in the rate <strong>of</strong> passage <strong>of</strong> the gases. Such a change<br />
would involve the danger that unburned vapours might escape<br />
from the tube. The brake acts by ensuring always that only equal<br />
amounts <strong>of</strong> gas pass through this zone in equal times. The resistance<br />
to the current <strong>of</strong> gas produced by this brake should be such that<br />
when the pressure in the regulator is equivalent to about 7-10 cm.<br />
<strong>of</strong> water 10 c.c. <strong>of</strong> gas pass through the section per minute. The
FILLING THE COMBUSTION TUBE 59<br />
amount <strong>of</strong> gas which passes is determined by means <strong>of</strong> a bubblecounter<br />
calibrated for the purpose in the following way when the<br />
brake-pad is being introduced. Since the resistance <strong>of</strong> the pad is<br />
considerably greater when hot than when cold its permeability must<br />
be tested while the tube is hot.<br />
Connect the combustion tube (with the brake-pad in position) to the<br />
drying apparatus, switch on the heat, adjust the regulator to a pressure<br />
<strong>of</strong> about 5-7 cm. and, as soon as temperature equilibrium has been<br />
reached, determine the number <strong>of</strong> bubbles passing in ten seconds, using a<br />
watch and having the three-way cock full open with air passing. Now<br />
connect the constricted end <strong>of</strong> the combustion tube with the aspirator<br />
(see below) and lower the levelling device until the same number <strong>of</strong><br />
bubbles passes every ten seconds. In a small measuring cylinder measure<br />
the volume <strong>of</strong> water which drops from the levelling tube <strong>of</strong> the aspirator<br />
in exactly one minute. Calculate the " constant " <strong>of</strong> the bubble counter<br />
from the duration <strong>of</strong> the test and number <strong>of</strong> bubbles. Now adjust the<br />
permeability <strong>of</strong> the brake-pad by pressing cautiously, at the same time<br />
controlling the rate <strong>of</strong> passage <strong>of</strong> bubbles in the counter so that 10 c.c.<br />
<strong>of</strong> gas per minute pass through the section <strong>of</strong> the tube. In doing this,<br />
rather exceed the 10 c.c. limit a little (up to 12 c.c.) since the part <strong>of</strong> the<br />
tube filling which lies beyond the brake-pad <strong>of</strong>fers a small additional<br />
resistance. Calibrate the bubble-counter finally only after the filling<br />
<strong>of</strong> the tube has been completed.<br />
After the brake-pad introduce a pad, 2 cm. long, <strong>of</strong> silver wool,<br />
preferably formed beforehand in an old combustion tube so that<br />
the fit is rather right and pressure on the brake-pad is avoided. Fix<br />
the silver wool in position with a small, loose pad <strong>of</strong> asbestos and,<br />
with continuous turning and gentle sidewards tapping <strong>of</strong> the tube<br />
(not jolting !), pour in a layer 14 cm. long, <strong>of</strong> copper oxide-lead<br />
chromate. Fix this also in position with a loose asbestos pad.<br />
Prepare the copper oxide-lead chromate as follows: Spread a thin<br />
layer <strong>of</strong> coarse copper oxide over a small iron plate, heat from above<br />
with a blow pipe until the glow is as bright as possible and sprinkle with<br />
a thin layer <strong>of</strong> finely powdered lead chromate. The chromate melts at<br />
once and spreads over the copper oxide forming a firmly adherent layer<br />
and causing the strips <strong>of</strong> copper oxide to stick together a little. Now<br />
turn the cake over and treat the under side in the same way. When the<br />
mass has cooled break it up gently in a mortar and remove powder and<br />
unduly large pieces with a sieve.<br />
After the copper oxide-lead chromate layer has been placed in<br />
position clean the tube very carefully with a large pad <strong>of</strong> cotton<br />
wool continuing until the wool is no longer coloured by the lead
60 THE ABSOKPTION APPAEATUS<br />
chromate dust. Then introduce successively a layer <strong>of</strong> silver wool<br />
1-5 to 2 cm. long, a small loose asbestos pad, and finally a loose pad<br />
<strong>of</strong> platinised asbestos 2-5 cm. long or a small roll <strong>of</strong> platinum-wire<br />
gauze 3 cm. long. After five successive combustions <strong>of</strong> compounds<br />
containing halogen or sulphur renew the last silver layer.<br />
Test the permeability <strong>of</strong> the filling as described above and carry<br />
out a final calibration <strong>of</strong> the bubble-counter. Burn out the whole<br />
length <strong>of</strong> the tube whilst a current <strong>of</strong> dry air or oxygen is passing.<br />
The tube is now ready for the combustion <strong>of</strong> nitrogen-free substances.<br />
Such substances are preferably burned in a current <strong>of</strong> oxygen<br />
instead <strong>of</strong> air.<br />
For the combustion <strong>of</strong> substances containing nitrogen reduce the<br />
5 cm. layer <strong>of</strong> copper oxide in a current <strong>of</strong> hydrogen in the manner<br />
described under nitrogen determination. After the reduction burn<br />
out the filling for half an hour in a gentle current <strong>of</strong> dry nitrogen,<br />
allow to cool in nitrogen and then expel the nitrogen with air.<br />
Repeat the reduction <strong>of</strong> the copper layer when necessary—at<br />
the earliest after four determinations. If carefully handled the combustion<br />
tube has a life <strong>of</strong> 100 analyses and more.<br />
The Absorption Apparatus. Filling this Apparatus.—Small thinwalled<br />
glass on tubes with two ground glass stoppers<br />
(Blumer-Berger tubes, Fig. 38) are<br />
used for absorbing the water and<br />
carbon dioxide produced during the<br />
combustion. The external diameters<br />
<strong>of</strong> the small side tubes and the external<br />
diameter <strong>of</strong> the constricted<br />
part <strong>of</strong> the combustion tube must<br />
all correspond exactly. One <strong>of</strong> the<br />
ground stoppers <strong>of</strong> calcium chloride<br />
tube serves as a "water trap"<br />
having a fine hole in its inner end.<br />
A capillary tube is sealed over this<br />
hole.<br />
Clean and dry the calcium chloride<br />
tube and fill it as follows : First<br />
slightly grease with vaseline the<br />
FIG. 38<br />
stopper with the capillary, keeping<br />
clear <strong>of</strong> the upper two millimetres, or alternatively removing the<br />
vaseline from this part with a cloth—in this way the expression <strong>of</strong>
THE ABSOKPTION APPAEATUS 61<br />
grease when the stopper is introduced is avoided. The ground<br />
joint should be just transparent and the stopper should turn only<br />
with considerable stiffness. Carefully remove excess <strong>of</strong> vaseline<br />
from the opening in the stopper and from the side tube with a roll <strong>of</strong><br />
cotton wool. Now lay a small pad <strong>of</strong> cotton wool on the lower<br />
stopper, pour in first a 1 cm. layer <strong>of</strong> coarsely granulated calcium<br />
chloride, fix this layer in position with small pad <strong>of</strong> cotton wool and<br />
then, with gentle sidewards tapping, pour in granulated calcium<br />
chloride (granules the size <strong>of</strong> millet grains) previously dried at<br />
180°-200° until the layer reaches to just below the upper stopper.<br />
After this layer has been fixed in position with a dried pad <strong>of</strong> cotton<br />
wool, insert the upper stopper first greasing it with vaseline as above<br />
and carefully wiping away excess vaseline. Loosely fill the hollow<br />
<strong>of</strong> the stopper with dry cotton wool.<br />
Since the calcium chloride contains basic constituents the filling<br />
must be saturated with carbon dioxide before the absorption tube is<br />
used. For this purpose connect the side tube which leads to the water<br />
trap to the Kipp apparatus, interposing a drying tube, pass a strong<br />
current <strong>of</strong> carbon dioxide for 10 minutes, close the outlet, and allow to<br />
stand for half an hour, maintaining the pressure <strong>of</strong> the Kipp. After<br />
200 c.c. <strong>of</strong> dry air have been drawn through the tube by means <strong>of</strong> the<br />
aspirator, the tube is ready for use.<br />
One filling suffices for at least fifteen analyses. It is preferable<br />
to renew the filling when that <strong>of</strong> the sodium hydroxide-asbestos tube<br />
is being renewed.<br />
Clean and dry the sodium hydroxide-asbestos tube and fill it as<br />
follows. Push a loose pad <strong>of</strong> cotton wool into the hollow <strong>of</strong> the<br />
lower stopper, suitably grease this and insert it. Lay another small<br />
pad on the lower stopper and then pour in, with gentle sidewards<br />
tapping, Merck's sodium hydroxide-asbestos until the tube is twothirds<br />
full. Now fix this layer in position with a small pad <strong>of</strong> cotton<br />
wool and introduce a layer 0-5 cm. deep, <strong>of</strong> ordinary not specially<br />
dried calcium chloride. Again fix in position with a loose pad <strong>of</strong><br />
cotton wool and fill to just below the stopper with dried calcium<br />
chloride (granules the size <strong>of</strong> millet grains) dried at 180°-200°.<br />
Grease the upper stopper with vaseline and insert it after pushing in<br />
another dried pad <strong>of</strong> cotton wool. The tube is now ready for immediate<br />
use. The filling suffices for at least fifteen determinations.<br />
As the sodium hydroxide-asbestos absorbs carbon dioxide the dirty<br />
grey colour <strong>of</strong> the absorbent becomes noticeably lighter and observa-
62 THE ASPIEATOE<br />
tion <strong>of</strong> the colour change alone indicates if the filling still suffices<br />
for the next analysis. As soon as all but 1 cm. <strong>of</strong> the sodium<br />
hydroxide-asbestos is exhausted, renew the filling.<br />
Since the vapour tension over the sodium hydroxide-asbestos is<br />
less than that over the specially dried calcium chloride, some<br />
ordinary not specially dried calcium chloride must be interposed<br />
between those two layers.<br />
Connect the absorption tubes to each other and to the combustion<br />
tube by means <strong>of</strong> pieces (lengths 2 and 1-5 cm. respectively) <strong>of</strong><br />
narrow-bored rubber tubing previously impregnated in a vacuum<br />
with vaseline (cf. p. 57) taking care that the ends <strong>of</strong> the side tubes,<br />
which are carefully but only slightly rounded smooth in the flame,<br />
fit together as closely as possible. In order to avoid possible<br />
difficulties due to differences in the diameters <strong>of</strong> the tubes mark the<br />
rubber tubing with arrows pointing in the direction <strong>of</strong> the gas<br />
current and join always at the same places. Moisten the inside <strong>of</strong><br />
the tubing with a trace <strong>of</strong> glycerol by pushing in a plug <strong>of</strong> cotton<br />
wool containing a very small amount <strong>of</strong> glycerol. This facilitates<br />
the insertion <strong>of</strong> the glass tubes. Before this is done it is absolutely<br />
essential that all excess <strong>of</strong> glycerol is removed with a dry plug <strong>of</strong> the<br />
wool.<br />
The Aspirator.—Since the closely packed absorption vessels <strong>of</strong>fer a<br />
resistance equivalent to several centimetres <strong>of</strong> water to the gas stream<br />
there must be sufficient pressure at the junction <strong>of</strong> the constricted part<br />
<strong>of</strong> the combustion tube with the calcium chloride tube to overcome this<br />
resistance when the absorption apparatus is opened. But to create<br />
this pressure would seriously endanger the quantitative determination<br />
<strong>of</strong> the products <strong>of</strong> combustion because the high concentration <strong>of</strong> these<br />
set up at this point would increase the possibility <strong>of</strong> leakage. The most<br />
effective remedy consists in maintaining within the junction a pressure<br />
as near as possible to the atmospheric pressure. For this purpose an<br />
aspirator is attached to the apparatus so that a determined, easily<br />
variable diminished pressure can be maintained in the absorption<br />
apparatus.<br />
The arrangement <strong>of</strong> the aspirator can be seen in the diagram. The<br />
levelling tube is inserted into the opening through a cork (not a rubber<br />
stopper) in such a way that the tube can be moved to any desired level.<br />
The inlet tube, which is doubly bent downwards at right angles, carries<br />
a glass stop-cock which makes it possible to stop the action <strong>of</strong> the<br />
aspirator without changing the position at which the levelling tube has<br />
been set. An ordinary rubber tube connects the levelling tube with a<br />
small calcium chloride tube which has two side tubes bent at right angles.
CAEEYING OUT THE COMBUSTION 63<br />
During the analysis the calcium chloride tube is attached directly to the<br />
sodium hydroxide-asbestos tube. When the apparatus is not in use<br />
this calcium chloride tube is closed with a rubber cap.-<br />
CARRYING OUT THE COMBUSTION<br />
Weighing.—The chief difficulty in weighing the absorption<br />
apparatus lies in avoiding the errors due to the film <strong>of</strong> water which<br />
adheres to the surface <strong>of</strong> the glass, especially since the state <strong>of</strong> this<br />
film varies very greatly according to the external conditions. For<br />
this reason the absorption vessels must be treated in exactly the<br />
same way before and after the analysis and must be weighed after<br />
exactly equal periods since the difference in weight is accurately defined<br />
only under these " determined conditions ".<br />
First carefully wipe the filled sodium hydroxide-asbestos tube<br />
with a few slightly moistened flannel cloths and then wipe the whole<br />
tube with two chamois leather cloths, starting at the middle and<br />
moving the cloths with a twisting motion and pressing gently.<br />
Avoid undue rubbing and strong pressure. Now wipe out the side<br />
tubes with a clean plug <strong>of</strong> cotton wool wrapped round an iron wire.<br />
Avoid wiping too near the stopper since otherwise some vaseline<br />
may easily be removed. Finally, again wipe the absorption tubes<br />
with two small dry chamois leather cloths which should slip easily<br />
over the surface. Then, without touching the tube with the fingers,<br />
lay it on a wire stand (fountain-pen stand) close beside the balance,<br />
noting the exact time at which it is put down.<br />
In the same way prepare the calcium chloride tube for weighing.<br />
Weigh the substance preferably during the period in which the combustion<br />
tube is cooling (see below). .<br />
Now determine the zero point <strong>of</strong> , - T, [I ,<br />
the balance. Then grasp the sodium ^A—.Jl « 1 ^<br />
hydroxide-asbestos tube, which must not U<br />
be touched with the fingers after wiping,<br />
with the small dry chamois leather cloth,<br />
open the stop-cock (stopper) for a short<br />
time so as to permit equalisation <strong>of</strong> pres- FIG. 39<br />
sure, and, using an aluminium-wire fork<br />
(Fig. 39) lay the tube on a small wire frame on the left-hand pan <strong>of</strong><br />
the balance. The frame supports the tube at two points. Then<br />
put on the counterpoise (always use the same weights as counter-
64 CAEEYING OUT THE COMBUSTION<br />
poise) and 10 minutes after wiping the tube determine its approximate<br />
weight by adding centigramme weights until the rider<br />
can be set as near the beginning <strong>of</strong> the scale as possible. During<br />
the fifteenth minute determine the weight accurately. Directly<br />
thereafter determine the weight <strong>of</strong> the calcium chloride tube.<br />
When the combustion has been completed weigh the absorption<br />
vessels after exactly similar treatment and exactly the same time.<br />
When the weight has been exactly determined in the fifteenth minute<br />
rapidly put on the number <strong>of</strong> centigramme weights .corresponding<br />
to the increase in weight, move the rider to the corresponding notch<br />
at the beginning <strong>of</strong> the scale and again check the swing, which will<br />
now be somewhat different owing to the deviation <strong>of</strong> the weights<br />
from the reading given by the rider. By proceeding in this way<br />
one can avoid using additional weights, which would first have to<br />
be standardised, and can weigh by moving the rider alone after the<br />
next combustion.<br />
Weigh the substance in a small open platinum boat; weigh hygroscopic<br />
substances in a small weighing bottle.<br />
To clean the boat boil it in a test tube with dilute nitric acid,<br />
attach it to a platinum wire, and ignite it for a short time in the<br />
(non-luminous) Bunsen flame. Then set it to cool for about twenty<br />
seconds on a nickelled copper block.<br />
With a pair <strong>of</strong> forceps place the empty boat on the pan <strong>of</strong> the<br />
balance and carefully weigh accurately to 0-01 mg. Set the boat<br />
on a clean piece <strong>of</strong> paper, put in the substance, brush the outside<br />
clean with a fine hair brush, and determine the increase in weight<br />
with an accuracy <strong>of</strong> 0-01 mg. For C and H determinations weigh<br />
20-30 mg. After weighing, set the boat again on the copper block<br />
and cover with a small glass dish.<br />
THE COMBUSTION<br />
Switch on the current in the electric furnace while the absorption<br />
apparatus is cooling, at the same time passing air through the tube<br />
at the rate employed during analyses. 1 If the tube has not previ-<br />
1 When heating begins it will be observed that there is a distinct decrease in the<br />
rate <strong>of</strong> flow <strong>of</strong> bubbles in the counter although the adjustment <strong>of</strong> the pressure<br />
regulator remains unaltered. This decrease occurs because the brake-pad prevents<br />
immediate attainment <strong>of</strong> equilibrium following the rise in pressure caused by the<br />
increase in temperature. Thus every increase <strong>of</strong> pressure in the tube causes a<br />
diminution <strong>of</strong> the rate <strong>of</strong> flow <strong>of</strong> bubbles and hence greatly facilitates accurate<br />
control <strong>of</strong> the process <strong>of</strong> combustion during the analysis.
THE COMBUSTION 65<br />
ously been specially dried, or if it has been out <strong>of</strong> use for a long time,<br />
heat the empty part <strong>of</strong> the tube, before beginning a series <strong>of</strong> analyses,<br />
with a Bunsen burner after the furnace has reached steady temperature.<br />
Employ a small roll <strong>of</strong> wire gauze and carefully shield the<br />
rubber stopper with an asbestos plate, beginning to heat at a distance<br />
<strong>of</strong> 1 cm. from the stopper. When heating with the burner<br />
has extended to the furnace, remove the burner and slip the roll<br />
<strong>of</strong> wire gauze back to the end <strong>of</strong> the tube so that the part <strong>of</strong> the<br />
tube adjacent to the furnace cools again ready for the insertion <strong>of</strong><br />
the boat with the substance.<br />
After the absorption apparatus has been weighed push the side<br />
tube <strong>of</strong> the calcium chloride tube which leads to the water trap halfway<br />
into the 1 -5 cm. connecting piece <strong>of</strong> rubber tubing; in the same<br />
way attach the other end <strong>of</strong> the tube to the side tube <strong>of</strong> the sodium<br />
hydroxide-asbestos tube which leads directly to sodium hydroxideasbestos,<br />
using the 2 cm. connecting tube and taking care that the<br />
ends <strong>of</strong> the tubes fit together as closely as possible, and attach the<br />
absorption apparatus to the stand. Now rapidly check the rate <strong>of</strong><br />
flow <strong>of</strong> the bubbles, using a watch (number <strong>of</strong> bubbles in ten seconds)<br />
and, if necessary, adjust the pressure regulator so that 9-10 c.c. <strong>of</strong><br />
air (or oxygen) pass per minute as determined by means <strong>of</strong> the<br />
calibrated bubble-counter.<br />
Failure <strong>of</strong> the bubble-counter is frequently due to the increase in<br />
concentration <strong>of</strong> the alkali which results from long use. If such<br />
"failure " occurs introduce fresh (but rather more dilute) alkali. Then<br />
calibrate the bubble-counter anew. Another source <strong>of</strong> error is the sticking<br />
together <strong>of</strong> the calcium chloride granules in the drying apparatus or<br />
in the drying tube attached to the gas wash-bottle. Take the greatest<br />
care to prevent the alkali flowing from the bubble-counter into the<br />
rubber tube leading to the three-way cock.<br />
Now fit the calcium chloride tube closely to the constricted part<br />
<strong>of</strong> the combustion tube and connect the sodium hydroxide-asbestos<br />
tube to the calcium chloride tube <strong>of</strong> the aspirator. Then remove<br />
the rubber stopper from the combustion tube, push back the stand<br />
carrying the drying apparatus so as to make more room, raise the<br />
copper block with the boat to the opening <strong>of</strong> the combustion tube,<br />
with the forceps insert the boat, push it inwards 4-5 cm. up to the<br />
furnace with a clean glass rod <strong>of</strong> suitable size, taking care not to tip<br />
the boat over, insert the rubber stopper loosely into the tube,<br />
moistening the stopper if necessary with a very thin film <strong>of</strong> glycerol,
66 THE COMBUSTION<br />
and gently press the jet <strong>of</strong> the drying apparatus into the bore <strong>of</strong> the<br />
stopper until the tip projects just beyond the inner surface. Insert<br />
the substance as rapidly as possible so that no moisture from the<br />
atmosphere passes into the combustion tube.<br />
Now open the cocks on the absorption apparatus and the cock<br />
on the aspirator, and make sure that the previously determined rate<br />
<strong>of</strong> flow <strong>of</strong> the bubbles in the counter is maintained. A difference<br />
<strong>of</strong> 1-2 units in the number <strong>of</strong> bubbles passing in ten seconds has no<br />
detrimental effect. If necessary, restore the former rate <strong>of</strong> flow <strong>of</strong><br />
the bubbles by lowering or raising the levelling tube <strong>of</strong> the aspirator.<br />
(Collect the water which drops from the aspirator during the analysis<br />
in a 500 c.c. measuring cylinder). Then place in position the copperwire<br />
frame which conducts the heat from the furnace to the constricted<br />
part <strong>of</strong> the tube and to the side tube <strong>of</strong> the calcium chloride<br />
tube so that the metal touches the glass. Condensation <strong>of</strong> water in<br />
the side tubes is thus absolutely prevented.<br />
Now begin the actual combustion. Take care that the gas washbottles<br />
always remain filled with air (or oxygen) during the analysis<br />
so that one bubble is released every ten to fifteen seconds. As soon<br />
as the part <strong>of</strong> the tube inside the furnace has reached red heat push<br />
forward the 5 cm. roll <strong>of</strong> wire gauze so that its front end reaches<br />
almost to the boat and place the non-luminous flame <strong>of</strong> the Bunsen<br />
burner under the back end <strong>of</strong> the roll. After a short time the fall<br />
in the rate <strong>of</strong> flow <strong>of</strong> the bubbles which occurs as heating begins is<br />
no longer observed. Usually the portion <strong>of</strong> the substance in the rear<br />
part <strong>of</strong> the boat begins to melt, distil, or sublime after a few minutes.<br />
Never move the roll and the Bunsen burner forward until the changes<br />
which the substance undergoes have completely ceased. Then, approximately<br />
every two minutes, push the roll forward two or three<br />
millimetres and follow with the burner so that it always rests under<br />
the rear end <strong>of</strong> the roll. Temporary decrease in the rate <strong>of</strong> flow <strong>of</strong><br />
the bubbles in the counter occurs while these movements are being<br />
made. Check this decrease as much as possible by adjusting the<br />
movements in such a way that there is always an excess <strong>of</strong> oxygen.<br />
Then continue the movements as before when the original rate <strong>of</strong><br />
flow has been restored. Keep a continual watch on the behaviour <strong>of</strong><br />
the substance and also on the bubble-counter. Avoid moving too<br />
rapidly as otherwise the vapours in the tube strike back. On no<br />
account should the flow <strong>of</strong> bubbles stop or the liquid move backwards.<br />
In most cases a large drop <strong>of</strong> liquid forms on the floor <strong>of</strong>
THE COMBUSTION 67<br />
the tube immediately in front <strong>of</strong> the boat as a result <strong>of</strong> condensation.<br />
This very appreciably simplifies the conduct <strong>of</strong> the combustion<br />
since the effect <strong>of</strong> the regulation <strong>of</strong> temperature can be very accurately<br />
observed in the changes which the drop undergoes. The<br />
whole art <strong>of</strong> carrying out a combustion consists then in gradual,<br />
patient evaporation <strong>of</strong> the drop, remembering that the amount <strong>of</strong><br />
heat conducted increases greatly as soon as the burner reaches<br />
the boat, and consequently that the rate <strong>of</strong> movement must be<br />
correspondingly reduced. As soon as the last portion <strong>of</strong> the liquid<br />
has evaporated, heat with the flame (without wire gauze) the part <strong>of</strong><br />
the tube in which the boat rests until tube and boat just begin to<br />
glow ; in the same way rapidly bring the part <strong>of</strong> the tube between<br />
boat and furnace to a dull red heat. Most <strong>of</strong> the carbon produced<br />
during the decomposition <strong>of</strong> the substance is thus rapidly burned ;<br />
if necessary direct the flame also on the tube from above. If<br />
carbonaceous material difficult to burn forms an adherent layer on<br />
the Wall <strong>of</strong> the tube during the decomposition <strong>of</strong> the substance the<br />
following little trick <strong>of</strong>ten helps. Allow the material temporarily<br />
to cool and so to absorb oxygen. Then heat again. The material<br />
burns rapidly, especially if a current <strong>of</strong> oxygen moving at the same<br />
rate as the air current which it replaces is substituted after the liquid<br />
has evaporated. But oxygen need only be used thus when the<br />
material burns with very great difficulty. If oxygen is used, replace<br />
it by air as soon as the carbon has been completely burned so as to<br />
protect the layer <strong>of</strong> reduced copper.<br />
During the combustion the rate <strong>of</strong> flow <strong>of</strong> bubbles in the counter<br />
<strong>of</strong>ten increases rather appreciably because the rapid absorption in the<br />
sodium hydroxide-asbestos tube <strong>of</strong> the carbon dioxide produced causes<br />
a slight decrease in the pressure. If this happens reduce the rate <strong>of</strong><br />
dropping <strong>of</strong> water from the aspirator or even stop it altogether temporarily.<br />
No harm is done by this decrease in pressure. Should there be<br />
any small leaks at the constricted parts <strong>of</strong> the tube there would, it is<br />
true, be a danger that air might be sucked in. In view <strong>of</strong> the short<br />
duration <strong>of</strong> the reduction in pressure, however, the errors caused would<br />
have no appreciable effect on the determination. Obviously no<br />
" adjustment " <strong>of</strong> the flow from the aspirator must be made while the<br />
reduced pressure prevails. The former rate <strong>of</strong> dropping is automatically<br />
restored.<br />
As soon as the burner has reached the furnace (usually fifteen to<br />
twenty minutes, or for substances which burn with very great difficulty,<br />
up to thirty minutes, are required) move the roll and the
68 THE COMBUSTION<br />
burner back again to the end <strong>of</strong> the tube and push the furnace so far<br />
back that most <strong>of</strong> the layer <strong>of</strong> reduced copper extends outside the<br />
furnace. Thus, for the most part, the reduced layer is preserved for<br />
the next analysis. Now begin immediately to drive the products<br />
<strong>of</strong> combustion completely into the absorption apparatus by passing<br />
a further 180 c.c. <strong>of</strong> air through the tube. While the air is passing<br />
through, again ignite the empty part <strong>of</strong> the tube for a short time,<br />
beginning 1 cm. from the rubber stopper, using the burner and roll <strong>of</strong><br />
gauze. When 150 c.c. <strong>of</strong> water have been collected switch <strong>of</strong>f the<br />
current in the furnace. When the air current has been stopped close<br />
the cock on the aspirator, then close the cocks <strong>of</strong> the absorption<br />
apparatus, detach them from the combustion tube, close it with a<br />
rubber cap, and let it cool, maintaining the pressure <strong>of</strong> air from the<br />
gas holder. In this way the tube is ready for immediate use in the<br />
next analysis. Weigh the absorption vessels after preparing them<br />
suitably for the purpose (see below).<br />
Liquids.—Weigh liquids in a small hard glass tube 1 about 4 cm.<br />
long having glass supports (legs) at the open end and a ground glass<br />
stopper. Sealed to the closed end is a small glass hook by means <strong>of</strong><br />
which the weighing tube can be moved in the combustion tube with<br />
a bent wire. Clean the tube and drop in a small crystal <strong>of</strong> potassium<br />
chlorate, melt the crystal over a small flame and let it solidify again.<br />
After it has cooled, accurately weigh the prepared tube to 0-01 mg.<br />
on a suitable wire frame and pour in from a fine capillary tube 20-30<br />
mg. <strong>of</strong> the liquid to be analysed. Insert the stopper when weighing<br />
volatile substances. For combustion push the tube with the substance,<br />
open end towards the filling, into the combustion tube to<br />
within 7-9 cm. <strong>of</strong> the furnace. If the tube is weighed stoppered,<br />
loosen the stopper immediately before introducing into the combustion<br />
tube, but leave the stopper in the tube. The stopper also<br />
has a small glass hook sealed to it.<br />
When carrying out the combustion <strong>of</strong> liquids heat somewhat<br />
more carefully than is indicated above for solids, since liquids are<br />
more volatile.<br />
Weighing the Absorption Apparatus.—Prepare the absorption<br />
apparatus for weighing and weigh, in exactly the same way as described<br />
on p. 63.<br />
While the combustion tube is cooling withdraw the boat with a<br />
hooked platinum wire, ignite for a short time in the non-luminous flame<br />
1 A. Friedrich, Z. angew. Chem., 1932, 45, 477.
DETERMINATION OF HALOGEN, SULPHUR, ETC. 69<br />
<strong>of</strong> a Bunsen burner, allow to cool (on the copper block), and weigh out<br />
the substance for the next analysis.<br />
Immediately after the weight <strong>of</strong> the absorption vessels has been<br />
finally determined, do not forget to place on the pan the number <strong>of</strong><br />
centigramme weights equivalent to the increase in weight and, after<br />
moving the rider to the appropriate notch at the beginning <strong>of</strong> the scale,<br />
determine the new tare.<br />
Calculation.—The percentages <strong>of</strong> carbon and hydrogen can be<br />
calculated by means <strong>of</strong> the following formulae :<br />
0/ p_C02 found 300<br />
'° ~ substance 11 '<br />
H2O found<br />
'° substance<br />
Use Kiister's logarithm tables. The limits <strong>of</strong> error are : for<br />
carbon ± 0-3 per cent, for hydrogen -(-0-2 and - 0-1 per cent. Good<br />
analyses give about 0-1 per cent C too little and 0-1 per cent H too<br />
much.<br />
III. DETERMINATION OF HALOGEN, SULPHUR, AND<br />
OTHER ELEMENTS<br />
If a substance contains yet other elements besides carbon,<br />
hydrogen, oxygen, and nitrogen, the former are either determined<br />
by oxidising the substance in a sealed tube by heating with red<br />
fuming nitric acid (Carius) or by burning on a platinum catalyst<br />
in a current <strong>of</strong> oxygen (Dennstedt). Halogens are determined as<br />
silver halide, iodine preferably as iodic acid, sulphur as barium<br />
sulphate, phosphorus as magnesium pyrophosphate.<br />
1. DETERMINATION OF HALOGEN BY THE CAEIUS METHOD<br />
For the determination the following apparatus and chemicals<br />
are required :<br />
Hard glass (Jena) tubes for sealing (length 35 cm., internal diameter<br />
2-5 cm., wall thickness 1-2 mm.). 1<br />
Red fuming nitric acid (d 1-5).<br />
Solid silver nitrate.<br />
Small filter tube with Jena glass fritted filter plate (13 f. G 2).<br />
Halogen-free alcohol and dilute nitric acid (1:100).<br />
Preparing the Carius Tube.—First clean the tube with bichro-<br />
1 The tubes can be used repeatedly (three or four times).
70 HALOGEN BY THE CAEIUS METHOD<br />
mate-sulphuric acid mixture, wash out with water, connect to a<br />
water-jet pump, and dry with gentle warming.<br />
Weigh the substance in a small tube having a stem 8-10 cm.<br />
long (Fig. 40) made in the laboratory from a suitable glass rod.<br />
When weighing, lay the tube on a<br />
small wire frame (Fig. 40). After<br />
the approximate weight <strong>of</strong> the tube<br />
has been determined, weigh out<br />
40 accurately to 0-01 mg. 20-30 mg.<br />
<strong>of</strong> substance for the halogen determination.<br />
Hold the Carius tube horizontally, insert the weighing<br />
tube as far as possible, bring into a vertical position, and let the<br />
substance slip into the Carius tube. Carefully replace the weighing<br />
tube on the balance and determine the exact weight <strong>of</strong> substance<br />
taken by re-weighing.<br />
According to the amount <strong>of</strong> substance taken add 60-90 mg. <strong>of</strong><br />
finely powdered silver nitrate (it is best to add one and a half times<br />
the amount which corresponds to the expected halogen content).<br />
Then, if the substance is only slowly attacked by nitric acid in the<br />
cold, add 1 -0-1 -5 c.c. <strong>of</strong> red fuming nitric acid. In the case <strong>of</strong> substances<br />
which react vigorously with nitric acid in the cold, hold the<br />
Carius tube obliquely and add the acid in a small round-bottomed<br />
tube (length 6 cm., width 0-8 cm.), cautiously allowing it to slide<br />
to the bottom <strong>of</strong> the Carius tube and taking care that substance and<br />
acid do not come into contact with each other.<br />
Sealing the Tube.—In addition to compressed air use oxygen from a<br />
cylinder connected to the blow-pipe when sealing the hard glass tube.<br />
Grasp the tube in the middle with the left hand. Taking care that<br />
the nitric acid does not escape from the small tube and reach the substance,<br />
move the Carius tube into a position as near to horizontal as<br />
possible and heat the end first with the luminous, then with the nonluminous<br />
flame, and finally with the flame reinforced with some oxygen<br />
until the glass s<strong>of</strong>tens, continually rotating the tube slowly throughout.<br />
Now fuse a glass rod on to the inside <strong>of</strong> the tube, draw against the other<br />
side, and, after this side also is attached to the rod, move the latter into<br />
a position co-axial with the tube. Heat the tube now a little further<br />
down, where it is still cylindrical, using first an almost completely<br />
luminous flame and then, admitting a moderate amount <strong>of</strong> oxygen,<br />
continue until the glass is s<strong>of</strong>t. Keep the tube rotating continuously<br />
and press very gently so that the walls collapse at this point; as soon as<br />
the glass has thickened greatly, remove from the flame and slowly draw
HALOGEN BY THE CAEIUS METHOD 71<br />
out to a thick-walled capillary. Seal this capillary in a fine-pointed<br />
flame, using oxygen. Allow the capillary to cool in a luminous flame<br />
and then place the tube in an iron case so that the capillary projects a<br />
few centimetres. When necessary pour into the case an appropriate<br />
amount <strong>of</strong> sand. As long as the tube remains sealed it must not be<br />
removed from the iron case or from the furnace room.<br />
Heating the Tube.—Place the iron case with its tube in a bomb<br />
or tube furnace in such a way that the end with the capillary is<br />
raised somewhat and directed towards the wall on which a shield is<br />
fixed and close the furnace. Several tubes may be heated simultaneously.<br />
Light all the burners and heat gradually to the desired<br />
temperature, regulating the gas supply at the main tap. For<br />
aliphatic halogen compounds (and many sulphur compounds) this<br />
temperature is about 250°, for the aromatic compounds (and sulphonic<br />
acids) it is about 300°. Most substances are completely<br />
oxidised after three to four hours, but in the case <strong>of</strong> aromatic compounds<br />
the heating is continued for some hours longer.<br />
Opening and Emptying the Tube.—When the tube is quite cold,<br />
remove the iron case from the furnace, expel with a luminous flame<br />
any liquid which may have collected in the capillary, and hold the<br />
latter in the tip <strong>of</strong> a blow-pipe flame (goggles!). After the compressed<br />
gases have perforated the s<strong>of</strong>tened glass, remove the tube<br />
from the case, make sure that the substance is completely decomposed<br />
; if necessary re-seal the tube and heat again. If the<br />
substance is completely decomposed, re-seal the capillary tube and<br />
direct a fine-pointed oxygen flame against the tube a little further<br />
down, where the shape is cylindrical, so that at this point the tube<br />
blows out. Now s<strong>of</strong>ten the glass with the fine-pointed oxygen flame<br />
at the sides <strong>of</strong> the opening produced and draw away glass with a glass<br />
rod so that a wide opening, extending two-thirds round the tube, is<br />
formed. When the connecting part has then been s<strong>of</strong>tened pull away<br />
the top <strong>of</strong> the tube sideways, at the same time forming a small spout.<br />
Clean the outside <strong>of</strong> the tube and cautiously dilute the contents<br />
with 10 c.c. <strong>of</strong> water. The small tube which contained the nitric<br />
acid rises to the surface. Grasp this tube with a pair <strong>of</strong> bone-tipped<br />
forceps, empty its contents into a beaker having a rounded bottom<br />
(depth 15 cm., width 3-3-5 cm.), and wash with distilled water.<br />
Break up the silver halide as much as possible with a glass rod and<br />
transfer the contents <strong>of</strong> the Carius tube quantitatively to the beaker,<br />
washing out repeatedly. With a glass rod remove any silver halide
72 HALOGEN BY THE CAEIUS METHOD<br />
which obstinately adheres to the walls, and wash out the last traces<br />
with a little (halogen-free) alcohol and a little water.<br />
Filtering and Drying the Silver Halide.—First heat the precipitate<br />
in the beaker on the boiling water bath. Heat silver iodide<br />
(and bromide) for two hours, since silver iodide forms with silver<br />
nitrate a solid compound which is only gradually decomposed by<br />
water. Further, when determining iodine, first reduce with sulphurous<br />
acid solution the silver iodate produced during the decomposition.<br />
For the filtration use a small filter tube with a fritted glass<br />
filter (cf. Fig. 41). Pour into the filter a suspension <strong>of</strong> finest asbestos<br />
(for Gooch crucibles) to form a layer 2-3 mm. thick after<br />
sucking dry at the pump. Before using the filter tube, pour in a<br />
little silver chloride precipitated in the cold. As soon as the filtrate<br />
is clear the tube is ready for use.<br />
Before the filtration, wash the tube with water, fill it with 96 per<br />
cent alcohol, connect to the pump, draw the alcohol through slowly,<br />
and dry the tube for ten minutes at 130-140° on the heated copper<br />
drying block, meanwhile drawing through a gentle current <strong>of</strong> air. To<br />
exclude dust carried in by the air, fit to the cup <strong>of</strong> the filter tube a<br />
clean cork stopper, free from pores and carrying a short glass tube<br />
filled with tightly packed cotton wool. (The short glass tube is<br />
provided with a stem.)<br />
Wipe the dried filter tube in the manner<br />
described for the absorption vessels (p. 63) and<br />
weigh it accurately fifteen minutes after laying<br />
down, taking note <strong>of</strong> the position <strong>of</strong> the zero<br />
point.<br />
Transfer the silver halide precipitate to the<br />
filter by means <strong>of</strong> a delivery tube (Fig. 41),<br />
previously carefully cleaned. Attach the delivery<br />
tube to the filter tube by means <strong>of</strong> a small<br />
rubber stopper. Lower the delivery tube to the<br />
•p 4, bottom <strong>of</strong> the beaker and draw over the precipitate<br />
at a moderate speed (about two drops<br />
per second). Then wash with a little alcohol and, when the alcohol<br />
has been drawn through, with a little dilute nitric acid (1 : 100).<br />
If necessary repeat the successive washing with a little alcohol<br />
and a little water. Finally wash with alcohol the end <strong>of</strong> the<br />
delivery tube which is in the filter tube, fill the cup <strong>of</strong> the filter
DETEKMINATION OF CHLOKINE AND BROMINE 73<br />
tube to the brim with alcohol and, as soon as this alcohol has been<br />
drawn through, dry the filter tube at 130-140° for ten minutes on<br />
the copper drying block, continuing the suction meanwhile. Weigh<br />
after fifteen minutes.<br />
The Carius method is trustworthy but time-consuming. It is<br />
perferable to determine iodine by Leipert's method (p. 76) and chlorine<br />
and bromine as follows.<br />
2. ARGENTOMETRIC DETERMINATION OF CHLORINE AND<br />
BROMINE BY MEANS OF ADSORPTION INDICATORS<br />
The substance is burned on a platinum catalyst in a stream <strong>of</strong><br />
oxygen in a tube packed with beads and the gaseous products <strong>of</strong><br />
combustion are absorbed in the front portion <strong>of</strong> the tube, which<br />
contains the beads moistened with 5 per cent hydrogen peroxide<br />
solution. Absorption is made certain and rapid by spreading the<br />
absorbing liquid over a large surface. Elementary halogen is converted<br />
into halogen ion by the hydrogen peroxide. After the tube<br />
has been washed out the halogen ions in the solution are determined<br />
by the method <strong>of</strong> K. Fajans, 1 —direct titration with neutral silver<br />
nitrate solution, using organic dyes as indicators (" adsorption indicators<br />
").<br />
The following are required for the determination:<br />
A hard glass combustion tube (length 60-70 cm., internal diameter<br />
0 - 9 cm., wall thickness 1 mm. ; the front portion <strong>of</strong> the tube is<br />
drawn out to a constriction and ends in a small thick-walled tube,<br />
1-2 cm. long and 1 mm. in internal diameter ; the non-constricted<br />
part <strong>of</strong> the tube is filled, for 28-30 cm. <strong>of</strong> its length, with pieces <strong>of</strong><br />
hard glass rod 2-3 mm. long and 2 mm. thick; these pieces are<br />
held in position by means <strong>of</strong> a spiral <strong>of</strong> hard glass sealed into the<br />
tube).<br />
Three pieces <strong>of</strong> platinum-wire gauze each 5 cm. long.<br />
Acid-free perhydrol (Merck's).<br />
Neutral silver nitrate solution 0-02 N.<br />
0'0l per cent solution <strong>of</strong> dichlor<strong>of</strong>luorescein in 60 per cent alcohol<br />
(indicator for determination <strong>of</strong> Cl').<br />
0-1 per cent aqueous solution <strong>of</strong> eosin sodium (indicator for determination<br />
<strong>of</strong> Br').<br />
1 K. Fajans and H. Wolff, Z. anorg. Chem., 1924, 137, 221 ; cf. I. M. Kolth<strong>of</strong>f,<br />
Z. anal. Chem., 1927, 70, 369 ; 1927, 71, 235 ; J. Amer. Chem. Soc, 1929, 51, 3273 ;<br />
B. Bobianski, Z. anal. Chem., 1931, 84, 225 ; F. Holscher, Z. anal. Chem., 1934,<br />
96, 308.
74 DETEKMINATION OF CHLOKINE AND BKOMINE<br />
Preparing the Combustion Tube.—Thoroughly clean the tube,<br />
insert a small mouthpiece filled with cotton wool and suck into the part<br />
containing the beads 5 per cent hydrogen peroxide solution, freshly<br />
prepared from perhydrol before beginning each series <strong>of</strong> analyses,<br />
until the liquid moistens the spiral. Then let the tube drain.<br />
To moisten the beads 2-3 c.c. <strong>of</strong> liquid are quite sufficient. Cover<br />
the part <strong>of</strong> the tube containing the beads with a clean test tube<br />
and lay the combustion tube on the combustion stand. Boil the<br />
platinum catalysts with dilute nitric acid (1 : 1), ignite them strongly<br />
and push them into the tube so that the end <strong>of</strong> the foremost rests<br />
about 6 cm. from the spiral and spaces about 2 cm. long remain<br />
between them. Now adjust the tube on the stand so that the part<br />
containing the beads and about 5 cm. <strong>of</strong> the empty part project.<br />
Support the projecting part on a forked stand. Slip an asbestos<br />
shield on to the tube so that the shield rests against the wall <strong>of</strong> the<br />
furnace, so retaining the heat. Over the part <strong>of</strong> the tube containing<br />
the catalysts slip a roll <strong>of</strong> iron wire gauze, 20 cm. long, cover this<br />
part, which is to be heated with a perforated tube burner, with a<br />
wire gauze ro<strong>of</strong> to retain the heat and, finally, slip on another roll<br />
<strong>of</strong> wire gauze 5 cm. long for use with the moveable burner (cf. Fig.<br />
42 p. 76).<br />
For the determination, weigh in a platinum boat, in the usual<br />
way, 20-30 mg. <strong>of</strong> substance and insert the boat into the tube.<br />
The boat should rest 6-7 cm. beyond the long roll <strong>of</strong> wire gauze.<br />
Now close the tube with a rubber stopper and a capillary tube<br />
drawn out to a fine point and connect to an oxygen gas holder.<br />
Between the gas holder and the capillary interpose a small bubblecounter<br />
containing 50 per cent potassium hydroxide solution.<br />
For the determination <strong>of</strong> halogen in liquids weigh the substance in<br />
the manner described for C and H determination and introduce the<br />
weighing tube into the combustion tube in such a way that the former<br />
rests about 8-10 cm. beyond the front end <strong>of</strong> the long wire gauze roll.<br />
For liquids which burn with very great difficulty substitute ammonium<br />
nitrate for the potassium chlorate.<br />
Carrying out the Combustion.—After introducing the substance<br />
adjust the precision clip so that a current <strong>of</strong> oxygen passes at the<br />
rate <strong>of</strong> 7 to 9 c.c. per minute (calibration <strong>of</strong> the bubble-counter with<br />
the aspirator, cf. p. 59) and heat the platinum catalysts to bright<br />
red heat with the tube burner. As soon as this degree <strong>of</strong> heat has<br />
been attained push the small roll <strong>of</strong> wire gauze to within a few
DETEKMINATION OF CHLOKINE AND BROMINE 75<br />
millimetres <strong>of</strong> the boat and set the moveable burner with the flame<br />
made non-luminous, under the back end <strong>of</strong> the roll. Now wait<br />
until the changes which the substance undergoes have ceased, and<br />
then move the roll and the burner forward about 2-3 mm. every<br />
two minutes. In the case <strong>of</strong> substances which distil after melting<br />
proceed very carefully and wait until the distillate, which collects<br />
as a drop in the empty part <strong>of</strong> the tube between boat and catalyst,<br />
no longer increases in size. As soon as the edge <strong>of</strong> the Bunsen<br />
flame impinges below the boat, stop the movement and carefully<br />
observe whether or not the distillate evaporates appreciably while<br />
the burner is at rest. At least half an hour is required for the combustion<br />
<strong>of</strong> the substance. If less time is taken complete combustion<br />
and quantitative absorption cannot be assured.<br />
For the combustion <strong>of</strong> liquids move the small roll <strong>of</strong> wire gauze,<br />
before burning begins, to within 1-3 cm. at most, according to the<br />
volatility <strong>of</strong> the substance, <strong>of</strong> the small weighing tube and wait; when<br />
distillation begins, until it has ended, keeping the burner at rest. Then<br />
continue slowly as described above.<br />
Washing out the Tube and Titrating.—After the tube has cooled<br />
remove the boat, clamp the tube in a vertical position and replace<br />
the test tube by a clean conical flask (100-150 c.c). Then wash<br />
out the inside <strong>of</strong> the tube with a water jet (volume <strong>of</strong> water about<br />
10 c.c.) driving the liquid finally with small hand-bellows through the<br />
beads into the flask. Repeat this operation three times more, using<br />
10 c.c. <strong>of</strong> water each time, wash the constricted part <strong>of</strong> the tube,<br />
transfer the contents <strong>of</strong> the test tube also to the flask, and wash<br />
out the test tube.<br />
Before titrating, neutralise the mineral acid which has been<br />
produced with a few drops <strong>of</strong> saturated halogen-free sodium acetate<br />
solution so that the solution exhibits only a faint acetic acidity.<br />
For the determination <strong>of</strong> chlorine ions add to the solution 5-10<br />
drops <strong>of</strong> a 0-01 per cent alcoholic solution <strong>of</strong> dichlor<strong>of</strong>luorescein<br />
and titrate with neutral 0-02-0-025 N silver nitrate solution, using<br />
a micro-burette with 0-02 c.c. scale divisions. At the beginning<br />
<strong>of</strong> the titration the solution is only slightly opalescent; deep<br />
turbidity develops as the end-point is approached. At this stage<br />
continue to titrate cautiously with vigorous shaking until the silver<br />
halide sol suddenly coagulates to reddish-pink flocks.<br />
For the determination <strong>of</strong> bromine ions add to the solution 5-10<br />
drops <strong>of</strong> a 0-1 per cent aqueous solution <strong>of</strong> eosin sodium. In this
76 DETEKMINATION OF IODINE<br />
titration the end-point is very sharp ; until this point is all but<br />
reached the strongly opalescent solution remains transparent.<br />
Meanwhile the indicator acquires a shade which tends more towards<br />
blue. On the addition <strong>of</strong> the next drop the solution suddenly loses<br />
its transparency and the silver halide, when vigorously shaken,<br />
separates with an intensely reddish-pink colour.<br />
Titrate rather rapidly in diffused daylight. Avoid direct sunlight,<br />
because the sensitivity to light <strong>of</strong> the silver halide is greatly increased<br />
by the sensitising action <strong>of</strong> the dye.<br />
Limits <strong>of</strong> error in these determinations : ± 1 per cent <strong>of</strong> the<br />
halogen content.<br />
The halogen ions produced during the combustion <strong>of</strong> an organic<br />
substance can naturally be determined in the usual way also—gravimetrically<br />
by precipitation with Ag'.<br />
3. VOLUMETRIC DETERMINATION OF IODINE BY THE METHOD<br />
OF LEIPERT AND MTJNSTER 1<br />
The substance is burned on a platinum catalyst in a stream <strong>of</strong><br />
oxygen and the iodine liberated is oxidised to iodic acid by bromine<br />
in acetic acid. After excess bromine has been removed with formic<br />
acid, potassium iodide is added to the solution, and the iodine liberated<br />
is titrated with thiosulphate. Since the amount <strong>of</strong> iodine titrated<br />
is six times the iodine content <strong>of</strong> the substance the method yields<br />
very accurate results.<br />
The following are required for the determination :<br />
A combustion tube (Fig. 42) <strong>of</strong> hard glass (internal diameter 0-9<br />
cm., length 55-60 cm.; length <strong>of</strong> the delivery tube 18 mm.,<br />
internal diameter 2 mm. A<br />
small constriction is made<br />
close to the point <strong>of</strong> attachment<br />
<strong>of</strong> the delivery tube).<br />
10 per cent solution <strong>of</strong> pure<br />
sodium acetate in 96 per cent<br />
FIG. 42 acetic acid.<br />
Bromine (free from iodine).<br />
Pure formic acid (80-100 per cent).<br />
Potassium iodide and 0-1 N sodium thiosulphate solution.<br />
Carrying out the Combustion.—Thoroughly clean and dry the<br />
1 T. Leipert, Mikrochem. (Pregl Festschrift), 1929, 266; W. Munster, Milcrochem.,<br />
1933, 14, 23.
DETEKMINATION OF SULPHUE 77<br />
tube. Boil the platinum-wire gauze catalysts with dilute nitric acid<br />
(1 : 1), ignite them strongly and push them into the tube until they<br />
rest close to the constriction. Round this part <strong>of</strong> the tube slip a<br />
roll <strong>of</strong> iron-wire gauze 20 cm. long and, in order further to retain the<br />
heat, place a ro<strong>of</strong> <strong>of</strong> iron-wire gauze on the combustion stand above<br />
the roll. The delivery tube clips into a receiver <strong>of</strong> the type shown<br />
in Fig. 41. The receiver contains 12-15 c.c. <strong>of</strong> the acetate-acetic<br />
acid solution and 10-12 drops <strong>of</strong> bromine.<br />
For the determination <strong>of</strong> iodine weigh out 20-30 mg. <strong>of</strong> substance<br />
in a small platinum boat and carry out the combustion in the manner<br />
described above for the other halogens. Adjust the rate <strong>of</strong> flow <strong>of</strong><br />
the oxygen to 4-5 c.c. per minute.<br />
After the tube has cooled remove the boat and catalysts and<br />
pour into the tube, holding it obliquely, about 4 c.c. <strong>of</strong> solution <strong>of</strong><br />
bromine in acetic acid in order to oxidise the iodine deposited in<br />
the constriction. The constriction retains the solution at this point.<br />
After ten minutes wash the contents <strong>of</strong> the receiver and tube<br />
quantitatively into a clean conical flask, containing a solution <strong>of</strong><br />
2 g. <strong>of</strong> sodium acetate in a little water.<br />
In order to use up the excess <strong>of</strong> bromine let a few drops (up to 0-5<br />
c.c.) <strong>of</strong> formic acid run down the wall <strong>of</strong> the flask, shaking vigorously<br />
meanwhile so that the bromine in the gaseous phase is also absorbed.<br />
Wait a fewseconds until thesolution has become decolorised and then<br />
add at once some dilute sulphuric acid and 1 -5 g. <strong>of</strong> potassium iodide.<br />
Shake, leave for five minutes, and titrate the liberated iodine with<br />
0-1 ./y thiosulphate solution from a micro-burette with 0-02 c.c. scaledivisions,<br />
adding starch when the colour has diminished to yellowand<br />
then continuing the titration until the colour disappears.<br />
Limits <strong>of</strong> error <strong>of</strong> the method : ±0-3 per cent.<br />
4. DETERMINATION OF SULPHUR BY THE CARIUS METHOD<br />
The determination <strong>of</strong> sulphur by the Carius method is carried<br />
out in the same way as is the determination <strong>of</strong> halogen, but, in place<br />
<strong>of</strong> the silver nitrate, anhydrous barium chloride is here used.<br />
The following are required for the determination :<br />
Hard glass Carius tube.<br />
Red fuming nitric acid (d 1-5).<br />
Solid barium chloride.<br />
Porcelain Gooch crucible for ignition with a protective saucer.<br />
(Crucible Al, depth 2-7 cm., capacity 6 c.c. Berlin State Porcelain.)
78 DETEKMINATION OF SULPHUE<br />
Preparing the Caxius Tube.—For the determination <strong>of</strong> sulphur<br />
weigh out, as in the halogen determination, 20-30 mg. <strong>of</strong> substance.<br />
Introduce the substance into the tube, add 130-200 mg. (according<br />
to the weight <strong>of</strong> substance taken) <strong>of</strong> previously dehydrated barium<br />
chloride, and slip cautiously into the Carius tube, held in a sloping<br />
position, a small tube containing 1-1 -5 c.c. <strong>of</strong> red fuming nitric acid,<br />
taking care that the substance and acid do not come into contact<br />
with each other.<br />
Seal, heat, and open the tube as described for the determination<br />
<strong>of</strong> halogen.<br />
Emptying the Tube and Determining the Barium Sulphate.—<br />
Clean the outside <strong>of</strong> the tube and transfer its contents with repeated<br />
washing with distilled water to a small ordinary type beaker.<br />
Remove barium sulphate which adheres obstinately to the wall <strong>of</strong><br />
the tube with a glass rod (not rubber capped). By alternate washing<br />
with a little alcohol and a little water transfer the last traces <strong>of</strong><br />
the barium sulphate to the beaker.<br />
Carefully clean the crucible with bichromate-sulphuric acid<br />
mixture before the nitration, wash with distilled water, and suck<br />
dry at the pump. Wipe the crucible with a clean cloth, place it in<br />
a porcelain ignition dish standing on a pipeclay triangle, dry by<br />
fanning with a small Bunsen flame, and then heat slowly, raising the<br />
temperature gradually until a dark red heat is attained. After<br />
heating for twenty minutes, cool in the air for five minutes and then<br />
transfer crucible and dish to a desiccator. Weigh the crucible<br />
(without the dish) after it has cooled in the desiccator for one hour.<br />
Heat the contents <strong>of</strong> the beaker to boiling, fix the weighed<br />
crucible in a filter tube attached to a filter flask and transfer the<br />
barium sulphate directly from the beaker to the crucible, the last<br />
traces being transferred by alternate washing with alcohol and<br />
water. Finally, fill the crucible again with water, suck dry at the<br />
pump, and prepare for weighing exactly as described above.<br />
Limits <strong>of</strong> error <strong>of</strong> the method : ±0-3 per cent.<br />
5. DETERMINATION OF SULPHUR BY COMBUSTION<br />
The determination <strong>of</strong> sulphur in the tube with bead packing is<br />
carried out in a manner analogous to that employed in the argentometric<br />
determination <strong>of</strong> halogen (see p. 73).<br />
The packing is moistened with 5-10 per cent hydrogen peroxide
DETEKMINATION OP HALOGEN 79<br />
solution, any lower oxidation products <strong>of</strong> sulphur which may be<br />
formed being converted into sulphuric acid.<br />
After preparing the tube carry out the combustion <strong>of</strong> the substance<br />
exactly as is described in detail for the halogen determination.<br />
Since complete absorption <strong>of</strong> sulphur trioxide by the absorbent<br />
requires a long period <strong>of</strong> contact, employ a slower current <strong>of</strong> oxygen<br />
(3-4 c.c. per minute) and, correspondingly, move the Bunsen burner<br />
forward more slowly. The combustion <strong>of</strong> the substance should<br />
require about one hour.<br />
After the combustion is finished wash out the tube as described<br />
for the halogen determination, collecting the liquid in a small clean<br />
beaker and add the contents <strong>of</strong> the test tube, washing it out also.<br />
Then add a clear filtered mixture <strong>of</strong> 2-3-5 c.c. <strong>of</strong> barium chloride<br />
solution (1 : 10) and 10 drops <strong>of</strong> dilute hydrochloric acid, cover with<br />
a clean watch-glass, heat to boiling, and continue until separation <strong>of</strong><br />
barium sulphate ceases. Immerse the beaker in cold water to cool<br />
and complete the determination as described in the preceding<br />
section.<br />
6. SIMULTANEOUS DETERMINATION OF HALOGEN AND SULPHUR<br />
If halogen and sulphur have to be determined simultaneously in<br />
one substance, first determine the halogen by the Carius method.<br />
Collect the filtrate from the silver halide in a carefully cleaned filter<br />
flask, transfer to a beaker <strong>of</strong> heat-resistant glass, dilute to 120-<br />
150 c.c, and precipitate the sulphuric acid from the boning solution<br />
with 1 per cent barium nitrate solution absolutely free from halogen.<br />
For washing the precipitate use distilled water, not water containing<br />
hydrochloric acid.<br />
7. DETERMINATION OF OTHER ELEMENTS<br />
Most <strong>of</strong> the other elements are determined by the methods <strong>of</strong><br />
inorganic analysis after organic material has been oxidised in nitric<br />
acid solution by the Carius procedure.<br />
Alkali and Alkaline Earth Metals are determined as sulphate.<br />
Weigh the substance in a quartz or platinum crucible, add a few<br />
drops <strong>of</strong> concentrated (for explosive or unstable substances use<br />
30-50 per cent acid) sulphuric acid and evaporate cautiously.<br />
Finally ignite at dull red heat.
80 DETEEMINATION OF OEGANIC GEOUPS<br />
IV. DETERMINATION OF ORGANIC GROUPS<br />
1. VOLUMETRIC DETERMINATION OF THE METHOXY AND<br />
BTHOXY GROUP 1<br />
The methyl <strong>of</strong> the CH3O group is converted into methyl iodide<br />
(Zeisel's method) by boiling with hydriodic acid and the methyl<br />
iodide is converted into the corresponding bromide with formation <strong>of</strong><br />
iodine bromide :<br />
The iodine bromide is oxidised to iodic acid by excess <strong>of</strong> bromine :<br />
BrI + 2Br2 + 3HaO = HIO3 + 5HBr.<br />
The excess <strong>of</strong> bromine is converted into hydrobromic acid by means<br />
<strong>of</strong> formic acid and, finally, after addition <strong>of</strong> potassium iodide, the<br />
iodine liberated is titrated with thiosulphate.<br />
Since, in this method, six equivalents <strong>of</strong> iodine are liberated for<br />
each alkoxyl group, the determination can be made with great<br />
accuracy even when the amounts <strong>of</strong> substance are very small.<br />
The following are required for the determination :<br />
5 c.c. <strong>of</strong> hydriodic acid (d 1-7 ; " for methoxyl determination ").<br />
10 c.c. <strong>of</strong> solution <strong>of</strong> pure sodium acetate in<br />
96 per cent acetic acid.<br />
Bromine free from iodine (best kept in a<br />
dropping funnel).<br />
Pure formic acid, 80-100 per cent.<br />
Sodium acetate (analytically pure).<br />
Potassium iodide and 0-1 N sodium thiosulphate<br />
solution.<br />
The apparatus (Fig. 43) is provided by<br />
the laboratory.<br />
Setting up and Preparing the Apparatus.—First<br />
pour into the washing tube<br />
(W) 3 c.c. <strong>of</strong> a suspension <strong>of</strong> about 150<br />
mg. <strong>of</strong> red phosphorus in water, the<br />
FIG. 43 phosphorus having been thoroughly purified<br />
with ammonia. Take care that none<br />
<strong>of</strong> the wash liquor gets into connecting tube. Into the receiver<br />
( ^I) P°ui 10 c.c. <strong>of</strong> the 10 per cent sodium acetate-acetic acid<br />
F. Vjebock and C. Brecher, Ber., 1930, 63, 2818, 3207.
DETEKMINATION OF THE METHOXY GEOUP 81<br />
solution, add 10-12 drops <strong>of</strong> bromine, mix well and tip the receiver<br />
so that about a third <strong>of</strong> the liquid passes into the second receiver<br />
( F2). Make the receiver fast to the apparatus with spiral springs.<br />
Then make ready a carbon dioxide Kipp apparatus, attach to it a<br />
wash bottle filled with dilute lead acetate solution, and connect to<br />
the apparatus for methoxyl determination with a rubber tube<br />
carrying a precision screw clip.<br />
For the determination <strong>of</strong> methoxyl weigh out in the manner<br />
described for determination <strong>of</strong> halogen 20-30 mg. <strong>of</strong> substance, using<br />
a small weighing tube. Transfer the substance to the reaction<br />
flask (K) and add a few small crystals <strong>of</strong> phenol and 0-5 c.c. <strong>of</strong><br />
acetic anhydride (or glacial acetic acid) in order to dissolve the substance.<br />
Then add about 0-2 g. <strong>of</strong> dry red phosphorus.<br />
Carrying out the Determination.—After introducing the substance<br />
connect the gas inlet tube <strong>of</strong> the reaction flask with the Kipp<br />
apparatus and immediately before attaching the flask to the apparatus<br />
pour in 5 c.c. <strong>of</strong> hydriodic acid, (d 1-7). Protect the receivers<br />
from radiant heat with an asbestos shield and for the same<br />
reason use the smallest possible glycerol bath (beaker) for heating<br />
the acid.<br />
After adjusting the speed <strong>of</strong> the gas stream so that only one<br />
bubble at a time passes through the receivers, heat the bath rapidly<br />
and maintain the temperature at 140°-150° during the determination.<br />
Neglect the temporary increase in the rate <strong>of</strong> flow <strong>of</strong> the gas ; as<br />
soon as the acid begins to boil the rate falls to its original level.<br />
After heating for one hour all the methyl iodide has certainly been<br />
carried over into the receivers. Detach them first and afterwards<br />
disconnect the Kipp apparatus from the reaction flask. The acid<br />
in the flask can be used without further treatment for three further<br />
determinations.<br />
When decomposing ethoxy compounds heat first under the small<br />
reflux condenser for half an hour, then diminish the cooling effect by<br />
allowing the water to run <strong>of</strong>f, and continue boiling for one hour.<br />
After removing the receivers run a few cubic centimetres <strong>of</strong><br />
water into the delivery tube and empty the contents into a 250 c.c.<br />
conical flask containing 1-5 g. <strong>of</strong> pure sodium acetate completely<br />
dissolved in a little water. Repeatedly wash out the receivers so as<br />
to make up the volume <strong>of</strong> liquid to about 100-150 c.c. Then run<br />
5-10 drops <strong>of</strong> pure formic acid down the wall <strong>of</strong> the flask and shake<br />
G
82 THE ACBTYL AND BENZOYL GEOUP<br />
round. If the operation is correctly carried out the colour <strong>of</strong> the<br />
bromine disappears in a few seconds. Shake vigorously so as to<br />
bring about absorption <strong>of</strong> the bromine in the gaseous phase. If<br />
the colour <strong>of</strong> the bromine does not disappear within a few minutes,<br />
the indication is that insufficient sodium acetate has been used.<br />
To the decolorised solution add some dilute sulphuric acid and<br />
about 1 g. <strong>of</strong> potassium iodide, cover the flask, and leave to stand for<br />
five minutes. Then titrate the iodine liberated with 0-1N thiosulphate<br />
solution from a micro-burette having 0-02 c.c. scale-divisions,<br />
adding starch solution when the colour has diminished to<br />
yellow and then continuing the titration until the colour disappears.<br />
1 c.c. <strong>of</strong> 0-1N thiosulphate solution corresponds to 0-51706 mg.<br />
<strong>of</strong> OCH3 and to 0-75067 mg. <strong>of</strong> OC2H5.<br />
2. DETERMINATION OF THE ACETYL AND BENZOYL GROUP X<br />
The substance is hydrolysed by boiling under reflux with 50<br />
per cent sulphuric acid and the acetic acid or benzoic acid produced<br />
is distilled in steam and titrated with sodium hydroxide solution,<br />
using phenolphthalein as indicator.<br />
The apparatus (Fig. 44) is supplied by the laboratory. The<br />
following are required for the<br />
determination:<br />
50 per cent sulphuric acid.<br />
Sodium hydroxide solution<br />
0-033 N.<br />
Carrying out the Determination.—<br />
Fill the bubblecounter<br />
with 50 per cent<br />
potassium hydroxide solution<br />
(non-frothing) and the<br />
U-tube and drying tube at-<br />
44 tached to it with calcium<br />
chloride.<br />
For the determination <strong>of</strong> acetyl or benzoyl weigh 20-30 mg. <strong>of</strong><br />
substance in the small weighing tube with long stem (see p. 70)<br />
and transfer to the reaction flask. Set the condenser in the reflux<br />
position, making the ground j oint C gas-tight with a drop <strong>of</strong> water,<br />
1 R. Kuhn and H. Roth, Ber., 1933, 66, 1274.
DETEKMINATION OF THE ACETYL GKOUP 83<br />
adjust the rate <strong>of</strong> flow <strong>of</strong> air through the apparatus to 30 bubbles<br />
per minute by regulating the precision screw clip and make the<br />
ground joint A gas-tight with a little moist phosphorous pentoxide.<br />
Make the joint <strong>of</strong> the funnel tube B gas-tight in the same way, run<br />
2-3 c.c. <strong>of</strong> the 50 per cent sulphuric acid into the flask, insert the<br />
glass rod S, and pour 1 c.c. <strong>of</strong> water into the funnel. Then heat<br />
the contents <strong>of</strong> the flask under reflux to boiling and continue to<br />
boil at a moderate rate.<br />
The hydrolysis <strong>of</strong> O-acetyl compounds is usually complete in<br />
thirty minutes, that <strong>of</strong> O-benzoyl compounds in sixty minutes. Up<br />
to three hours are required for the complete hydrolysis <strong>of</strong> N-acetyl<br />
and N-benzoyl compounds. The hydrolysis may be allowed to proceed<br />
over night, using some concentrated sulphuric acid.<br />
When the hydrolysis is complete carefully wash out the condenser<br />
with 10-12 c.c. <strong>of</strong> water. Then distil up to 5 c.c. <strong>of</strong> liquid<br />
into a small conical quartz flask. Use the condenser in the downward<br />
position and if necessary add a few " boiling capillaries " to<br />
the liquid in the flask. Eepeat the distillation three more times,<br />
each time adding 7 c.c. <strong>of</strong> water. Test the distillate (volume about<br />
20 c.c.) with some barium chloride for sulphuric acid (none should<br />
be present), boil for seven to eight seconds and titrate at once with<br />
0-033 N sodium hydroxide solution 1 from a micro-burette having<br />
0-02 c.c. scale-divisions. Use phenolphthalein as indicator and continue<br />
the titration until the colour becomes just pink and remams so<br />
for a few seconds. For the second titration distil 2 x 7 or 3 x 7 c.c. and<br />
for the third and fourth titrations only about 7 c.c. on each occasion.<br />
Example<br />
1st titration (about 20 c.c. <strong>of</strong> distillate) : 5-885 c.c. <strong>of</strong> alkali<br />
2nd „ ( „ 2x7 c.c. „ ): 0-680 c.c.<br />
3rd „ (,,2x7 c.c. „ ) : 0-040 c.c.<br />
4th „ (,,1x7 c.c. „ ) : 0-040 c.c.<br />
In the final titration not more than 0-05 c.c. <strong>of</strong> 0-033^ sodium<br />
hydroxide solution should be required.<br />
1 c.c. <strong>of</strong> 0-033 N sodium hydroxide solution corresponds to<br />
1-434 mg. <strong>of</strong> COCH3 or 3-5033 mg. <strong>of</strong> COC6H5. Limits <strong>of</strong> error <strong>of</strong><br />
the method + 0-5 per cent.<br />
In the apparatus described above C-methyl groups can also be<br />
1 Determine the factor <strong>of</strong> the alkali by titration with oxalic acid <strong>of</strong> approximately<br />
the same normality.
84 ZEKEVITINOFF'S METHOD<br />
determined by oxidation with chromic acid by the method <strong>of</strong><br />
K. Kuhn and F. L'Orsa. 1<br />
3. DETERMINATION OF ACTIVE HYDROGEN BY THE METHOD<br />
OF TSCHUGAEFF AND ZEREVITINOFF 2<br />
Prepare a Grignard solution in a distilling flask held in an<br />
oblique position and having a small condenser on the side tube (this<br />
condenser acts as reflux); use for this 20 c.c. <strong>of</strong> anisole 3 (amyl<br />
ether, 4 xylene) which has been distilled over sodium, 7 g. <strong>of</strong> methyl<br />
iodide, and 2 g. <strong>of</strong> magnesium; add also a few particles <strong>of</strong> iodine.<br />
If the reaction does not begin spontaneously, set it going by warming<br />
for a short time at 50° and complete by heating for one hour on the<br />
FIG. 45<br />
water bath. Then set the flask upright in the normal position and<br />
heat for a half an hour longer in a current <strong>of</strong> pure dry nitrogen so<br />
that the last traces <strong>of</strong> methyl iodide are removed. Pour <strong>of</strong>f the<br />
Grignard solution so obtained from unused magnesium or, better,<br />
filter with suction through a dry fritted glass filter and store in a<br />
well-closed bottle. For each determination use about 5 c.c. <strong>of</strong> this<br />
solution.<br />
The apparatus for the determination <strong>of</strong> active hydrogen is shown<br />
in Fig. 45. The Lunge nitrometer a, <strong>of</strong> which the levelling bulb is<br />
not shown in the sketch, is filled with saturated brine. By means <strong>of</strong><br />
the short calcium chloride tube b, interposed between the reaction<br />
vessel and the nitrometer, the access <strong>of</strong> water vapour to that vessel<br />
is prevented. For the determination weigh accurately, according to<br />
1<br />
Z. angew. Chem., 1931, 44, 847; Ber., 1933, 66, 1274.<br />
a<br />
Ber., 1907, 40, 2027.<br />
3 4<br />
Preparation, see p. 244.<br />
Preparation, see p. 117.
DETEKMINATION OF ACTIVE HYDKOGEN 85<br />
the molecular weight and hydroxyl content, 0-1-0-2 g. <strong>of</strong> the substance<br />
1 from a weighing bottle into the longer branch c <strong>of</strong> the welldried<br />
reaction vessel, cover with anisole or amyl ether, and dissolve<br />
by careful shaking. Then pour 5 c.c. <strong>of</strong> the Grignard solution from a<br />
graduated pipette into the other branch d and expel the air with dry<br />
nitrogen (essential!) Attach the reaction vessel by means <strong>of</strong> a clean,<br />
tightly fitting rubber stopper and a piece <strong>of</strong> rubber tubing to the<br />
calcium chloride tube <strong>of</strong> the nitrometer, from which the stop-cock has<br />
been removed, dip the reaction vessel into a beaker containing water<br />
at room temperature, wait for five minutes until temperature equilibrium<br />
has been attained, replace the stop-cock, and, by raising<br />
the levelling bulb, fill the nitrometer with brine. Then turn the<br />
cock through 90°, lower the levelling vessel, and put the reaction<br />
vessel into communication with the measuring tube by turning the<br />
cock again through 90°. Now remove the reaction vessel from the<br />
beaker, allow the solution <strong>of</strong> the substance to flow into the Grignard<br />
solution, pour the mixture backward and forward a few times, and<br />
shake until the meniscus in the measuring tube no longer falls and<br />
the evolution <strong>of</strong> methane is therefore at an end. Put the vessel back<br />
into the beaker, wait for ten minutes until it has regained the temperature<br />
which prevailed at the beginning <strong>of</strong> the experiment (check<br />
with a thermometer), and read <strong>of</strong>f in the usual way the amount <strong>of</strong><br />
methane produced. At the same time take the temperature <strong>of</strong> the<br />
gas with a thermometer hung on the measuring tube and also read<br />
the barometric height. Eeduce the volume to 0° and 760 mm.<br />
Calculation.—According to the equation RHn + nCH3.MgI—>•<br />
R.(Mg.I)n + nCH4 one mole <strong>of</strong> substance liberates nx22-4 litres <strong>of</strong><br />
methane where n is the number <strong>of</strong> atoms <strong>of</strong> active H ; a grammes<br />
a n.22400.o<br />
<strong>of</strong> substance = ^ moles liberate p c.c. <strong>of</strong> CH4. The volume<br />
found and reduced ( F() must be equal to volume calculated ( Fcalc)<br />
for one active H-atom (n = l), or, when there are several active<br />
H-atoms then F( must be a simple multiple <strong>of</strong> F^,,. It is<br />
convenient to express the result as the number <strong>of</strong> atoms <strong>of</strong> active<br />
H according to the ratio Vtj Fcalc. The limits <strong>of</strong> error amount to<br />
5-10 per cent.<br />
The meso-analytical determination <strong>of</strong> active hydrogen (using 20-30<br />
mg. <strong>of</strong> substance) is described in F. Holscher's primer.<br />
1 Of the compounds prepared by the student triphenylcarbinol, /S-naphthol,<br />
quinol, and benzoic acid may be used.
86 EAST'S METHOD<br />
V. DETERMINATION OF MOLECULAR WEIGHT<br />
The various methods are not described here since, as a rule, they<br />
are learned in the practical course in physics or physical chemistry.<br />
The cryoscopic process is much to be preferred to the ebullioscopic.<br />
The most frequently used solvents are benzene and glacial acetic<br />
acid, and the best apparatus is the closed one <strong>of</strong> Beckmann, with<br />
electromagnetic stirring.<br />
A very elegant and simple method by which the molecular weight<br />
<strong>of</strong> organic substances can be determined in a melting point apparatus<br />
was recently described by K. East. 1<br />
Camphor has a very high cryoscopic constant and its melting<br />
point is very greatly depressed by substances dissolved in it. The<br />
depression is about 8 times as great as that in benzene. EbeMene = 5 • 1,<br />
Ecamphor = 40. This means that a molar solution in camphor melts<br />
40° lower than the solvent, i.e. than camphor itself. Accordingly,<br />
even with relatively dilute camphor solutions the depressions obtained<br />
are so great that the sensitivity <strong>of</strong> an ordinary thermometer<br />
(which can be read to 0-25°) suffices completely for the determination.<br />
2<br />
Make the melting-point tubes as described on p. 40 from a<br />
clean test tube; the internal diameter should be about 4-5 mm.<br />
Cut <strong>of</strong>f pieces about 5 cm. long. Close the lower ends by sealing as<br />
uniformly as possible, also keeping the walls as thin as possible. By<br />
drawing the s<strong>of</strong>tened glass away sideways avoid reducing the bore<br />
more than a little.<br />
For introducing the substance and the camphor use a small<br />
tube widened above to form a funnel. Insert this into the tube,<br />
stand the tube in a cork support, and weigh on an ordinary analytical<br />
balance. Introduce about 10 mg. <strong>of</strong> substance, using as a ram a<br />
small glass rod <strong>of</strong> suitable diameter for pushing through the funnel,<br />
weigh accurately to 0-1 mg., introduce 100-125 mg. <strong>of</strong> camphor in<br />
the same way, and weigh again.<br />
Eemove the funnel and seal the tube in a micro-flame but do not<br />
draw out too finely. Now heat the contents in a bath <strong>of</strong> concentrated<br />
sulphuric acid at 180° so that a homogeneous melt is produced.<br />
1 Ber., 1922, 55, 1051, 3727. Abderhalden, Arbeitsmethoden, Abt. Ill, Teil A,<br />
p. 754.<br />
2 In the following description the procedure worked out by W. Minister is<br />
followed, by which, in contradistinction to that <strong>of</strong> East, the solidification point is<br />
determined instead <strong>of</strong> the melting point originally used.
DETEKMINATION OF MOLECULAK WEIGHT 87<br />
After cooling fix the tube to the thermometer by means <strong>of</strong> a rubber<br />
ring passed round the drawn-out portion and heat again in a melting<br />
point apparatus (Fig. 31) till a clear melt is formed, allow to cool,<br />
and thus determine the solidification point approximately. In order<br />
to obtain the accurate value, heat again, this time very carefully<br />
with the micro-flame, the tip <strong>of</strong> which should be about 4 cm. below<br />
the apparatus, until the contents <strong>of</strong> the tube, with the exception <strong>of</strong> a<br />
few quite small crystals adhering to the bottom, melt to a clear<br />
liquid. The temperature so observed lies usually 2° above the<br />
former solidification point. Now regulate the temperature by<br />
turning down the flame so that the temperature falls at about 1° per<br />
minute. In this way it is possible to ascertain very distinctly<br />
through a lens when the surviving crystals begin to grow. At<br />
this point read the temperature. As a check repeat the operation ;<br />
with careful working almost the same solidification point should<br />
again be found. It is desirable to surround the flame with a shield,<br />
a cylinder <strong>of</strong> glass or <strong>of</strong> paper 8 cm. in diameter, which should reach<br />
to the melting point apparatus.<br />
The solidification point <strong>of</strong> the camphor employed is determined<br />
beforehand in the same way. Use a quite pure preparation. If<br />
such is not available make sure <strong>of</strong> a homogeneous supply by melting<br />
together separate pieces.<br />
If the solidification temperature <strong>of</strong> camphor (177°) is depressed<br />
by A, and a = amount <strong>of</strong> substance, b = weight <strong>of</strong> camphor, then the<br />
, , . , „ 40.O.1000<br />
molecular weight M = j—-—.<br />
The limits <strong>of</strong> error are ± 5 per cent.<br />
To compounds which dissolve with difficulty in camphor, decompose<br />
at the temperature <strong>of</strong> melting, or react with camphor this<br />
method cannot, <strong>of</strong> course, be applied. In such cases use as " solvent<br />
" the hydrocarbon camphene, 1 which melts at 49°.<br />
1 Pirsch, Ber., 1932, 65, 862, 865.
C. PREPARATIVE PART<br />
ON THE PREVENTION OF ACCIDENTS<br />
Whoever sets about preparative work carelessly and thoughtlessly<br />
may easily come to harm. But even the careful are not secure against<br />
all danger. The serious accidents which, alas, again and again occur<br />
in chemical laboratories make it imperative that every worker in the<br />
laboratory should fully and seriously consider his duty towards his<br />
fellows.<br />
It is most important to protect the eyes. Strong goggles with stout<br />
glass must be worn in all vacuum and pressure work, and hence<br />
when distilling in a vacuum, evacuating a new desiccator for the<br />
first time, or working with sealed tubes, pressure bottles, or autoclaves.<br />
Goggles must also be worn when carrying out fusions with<br />
alkali and during all operations in which caustic or inflammable substances<br />
may spurt, and therefore, in particular, during all work with<br />
metallic potassium and sodium<br />
Many a serious accident has occurred in laboratories as a result <strong>of</strong><br />
working with metallic sodium. When handling it, therefore, every<br />
precaution must be taken, and no residues should be thrown into<br />
sinks or waste buckets. It should never be allowed to lie exposed,<br />
but should be immediately returned to the stock bottle or destroyed<br />
with 15 to 20 times its weight <strong>of</strong> alcohol. The use <strong>of</strong> the boiling<br />
water bath or <strong>of</strong> the steam bath is to be avoided when carrying out<br />
a reaction with metallic sodium or potassium. An oil or sand bath<br />
should always be used, even when distilling dried ether from sodium<br />
wire. Students should pay special attention to the soundness <strong>of</strong><br />
apparatus when working with sodium and potassium, and always<br />
bear in mind the consequences which may, in certain circumstances,<br />
result from the use <strong>of</strong> a leaky condenser or <strong>of</strong> a cracked flask. Protective<br />
goggles should invariably be worn.<br />
Work with explosive substances should never be done without<br />
wearing goggles, and the behaviour in the flame <strong>of</strong> unknown sub-
PKEVENTION OF ACCIDENTS 89<br />
stances should always first be tested with small amounts on a<br />
metallic spatula after the preparation itself has been put in a place<br />
<strong>of</strong> safety.<br />
In order to guard the eyes against unforseeable explosions,<br />
which can never be absolutely excluded, every worker in the laboratory<br />
should wear plain glasses, while not dispensing with goggles<br />
in the cases mentioned.<br />
Care must invariably be taken when working with ether and other<br />
volatile, readily inflammable liquids that no flame is burning in the<br />
neighbourhood. If a fire occurs, everything which may ignite must<br />
immediately be removed. The fire should then be extinguished with<br />
moist towels or by pouring on carbon tetrachloride, but not water.<br />
The best extinguisher is a small portable CO2 cylinder, which should<br />
be kept in every laboratory. A larger fire may be tackled by pouring<br />
on sand, but here also a large carbon dioxide cylinder is usually<br />
preferable.<br />
Parts injured with acids or caustic alkalis should first be washed<br />
thoroughly with water and then with bicarbonate solution or dilute<br />
acetic acid respectively. Slight burns should be washed with alcohol<br />
and then covered with linseed oil or an ointment.<br />
Cotton wool, bandages, and plaster must always be at hand. When<br />
serious accidents occur the nearest doctor should at once be called.<br />
When a caustic or irritant organic substance attacks the skin,<br />
washing with water is usually without effect. Immediate removal<br />
by washing with copious amounts <strong>of</strong> a suitable solvent such as<br />
alcohol or benzene is the procedure indicated. It must be borne in<br />
mind that the organic solvent itself facilitates the penetration <strong>of</strong><br />
the harmful substance into the skin and therefore the formation <strong>of</strong><br />
concentrated solutions on the skin must be avoided.<br />
Especial care is required when working with the following much<br />
used substances : hydrocyanic add, phosgene, dimethyl sulphate, the<br />
lower acid chlorides, chlorine, bromine, nitric oxide and nitrogen<br />
peroxide, carbon monoxide, sodium, and potassium. Large scale<br />
operations with these should be carried out in a special room ; in any<br />
case always in a good fume chamber.<br />
Undiluted halogen compounds <strong>of</strong> the aliphatic series, such as<br />
ethyl bromide, chlor<strong>of</strong>orm, brom<strong>of</strong>orm, and the like, should not be<br />
brought into contact with metallic sodium or potassium ; thus they<br />
must not be dried with these metals since very violent explosions<br />
may occur as a result <strong>of</strong> detonation (Staudinger).
90 EQUIPMENT REQUIRED BY THE BEGINNER<br />
EQUIPMENT REQUIRED BY THE BEGINNER<br />
I. APPARATUS<br />
Beakers, 100, 500, and 1000 c.c, one <strong>of</strong> each.<br />
Burette. 1<br />
Calcium chloride tubes, straight, 3.<br />
Cardboard for weighing (playing-cards).<br />
Condensers, Liebig type, one about 60 cm. long ; a shorter one,<br />
10-12 cm. long ; one <strong>of</strong> the Dimroth or coil type.<br />
Conical flasks, 50, 100, 250, 500 c.c, two <strong>of</strong> each.<br />
Copper wire for halogen test.<br />
Cork-borers.<br />
Corks, various sizes.<br />
Crystallising basins, glass, 3, 5, 7 cm., one <strong>of</strong> each.<br />
Distilling flasks, ordinary and Claisen types, 25, 50, 100 cc. one<br />
<strong>of</strong> each.<br />
Files, round and triangular, one <strong>of</strong> each.<br />
Filter flasks, 100, 500, 1000 c.c.<br />
Filter paper, a few sheets.<br />
Filter jars, 500 and 1000 c.c, one <strong>of</strong> each.<br />
Filter plates, porcelain, 1, 3, 5 cm.<br />
Filter tubes, long and short, 3 <strong>of</strong> each.<br />
Funnels, 2 <strong>of</strong> smallest size, one each <strong>of</strong> other sizes up to 12 cm.<br />
Cylindrical Buchner funnel, about 8 cm. Dropping funnel,<br />
25 c.c. capacity with short stem and 100 c.c. capacity with<br />
long stem.<br />
Glass buttons, for filtration, 2.<br />
Glass rods, 20 <strong>of</strong> various thicknesses and lengths, rounded at<br />
both ends but not thickened.<br />
Glass tubes, drawn out to form pipettes (dropping tube, p. 12).<br />
Glass tubing, straight and bent.<br />
Labels.<br />
Measuring cylinders, 10 c.c, 100 c.c.<br />
Melting-point tubes, thin (to be made by the student).<br />
Metal spatula.<br />
Mortar.<br />
1 The student should be able to carry out at once, at any time, the usual volumetric<br />
determinations. As a rale the readiness to carry out titrations in the<br />
organic laboratory is not so great as is urgently desirable.
EQUIPMENT EEQUIEED BY THE BEGINNEE 91<br />
Pipettes, 5, 10, 20 c.c, and at least 6 small ones. Also one <strong>of</strong><br />
2 c.c. capacity graduated in tenths <strong>of</strong> a c.c.<br />
Porcelain basins, 15, 20, 25 cm. in diameter.<br />
Porcelain spatulae, 3.<br />
Porous pot. Pieces <strong>of</strong> porous plate about 3 mm. across.<br />
Round-bottomed flasks, 50, 100, 250, 500 c.c, two <strong>of</strong> each.<br />
Scales (apothecaries, capacity 50-100 g. Protect knives from<br />
rust by smearing with vaseline). Set <strong>of</strong> weights for the balance,<br />
0-02-50-0 g.<br />
Scissors.<br />
Separating funnels, 500, 1000 c.c.<br />
Slides (microscope), 3.<br />
String.<br />
Test papers. Litmus, blue and red, turmeric, Congo. Potassium<br />
iodide-starch paper.<br />
Test tube holder.<br />
Test tubes, at least 50 <strong>of</strong> ordinary size, 20 <strong>of</strong> small size. Half <strong>of</strong><br />
the test tubes must always be kept clean and dry.<br />
Thermometers. One standardised for melting point determination<br />
and two others, including a short one, for ordinary use.<br />
Tongs.<br />
Towel.<br />
Vacuum desiccators, two large ones (16 and 18 cm. diameter).<br />
Wash-bottles, 2.<br />
Watch-glasses, chiefly small.<br />
II. SOLVENTS<br />
Acetic acid, glacial, 500 c.c.<br />
Acetone, 100 c.c.<br />
Alcohol, 96 per cent, one litre.<br />
Alcohol, absolute, 500 c.c.<br />
Benzene (over sodium wire), 500 c.c.<br />
Chlor<strong>of</strong>orm, 100 c.c.<br />
Ether, absolute, over sodium, 1 500 c.c.<br />
1 In order to prepare absolute ether the commercial product (1-2 1.) is first<br />
dried for one to two weeks over calcium chloride (weight about 10 per cent <strong>of</strong> the<br />
weight <strong>of</strong> the ether taken) and poured rapidly through a folded filter into a dry<br />
flask into which sodium wire is driven from a press. Until the evolution <strong>of</strong> hydrogen<br />
ceases, a calcium chloride tube, drawn out to a fine capillary so as to reduce the
92 EQUIPMENT EEQUIEED BY THE BEGINNEE<br />
Ethyl acetate, 250 c.c.<br />
Methyl alcohol, 250 c.c.<br />
Petrol ether, low-boiling, 250 c.c. (over sodium wire).<br />
Petrol ether, high-boiling, 500 c.c. (over sodium wire).<br />
Xylene (over sodium wire).<br />
III. REAGENTS, DRYING AGENTS<br />
Calcium chloride.<br />
Decolorising charcoal.<br />
Glycerol (bottle with a cork stopper carrying a glass rod).<br />
Hydrochloric acid, concentrated.<br />
Nitric acid, concentrated (d. 1-4) and fuming (d. 1-5).<br />
Potassium hydroxide, commercial and pure.<br />
Silver nitrate solution, 5 per cent.<br />
Sodium hydroxide solution, about 14 N (=40 per cent).<br />
Sodium metal.<br />
Sodium sulphate, anhydrous.<br />
Standard solutions: 0-12V-HC1,0-liV-NaOH, 0-liV-iodine solution,<br />
O-liV-thiosulphate solution.<br />
Sulphuric acid, pure, concentrated.<br />
<strong>Laboratory</strong> Notebook. 1<br />
Abstracts from the literature.<br />
IV. BOOKS<br />
evaporation <strong>of</strong> the ether, is fitted to the flask. For most purposes this absolute<br />
ether is used without further treatment.<br />
When evaporating large amounts <strong>of</strong> impure ether which has been exposed to<br />
the air for a long time, the p'ossibility <strong>of</strong> the occurrence <strong>of</strong> a violent explosion at<br />
the end <strong>of</strong> the evaporation, due to the presence <strong>of</strong> peroxides, must be taken into<br />
account. Such ether has a pungent odour, and liberates iodine from an acid<br />
solution <strong>of</strong> potassium iodide. The peroxides can be destroyed by shaking with a<br />
weakly acid solution <strong>of</strong> ferrous sulphate.<br />
1 From the outset the student should accustom himself to keep a notebook in<br />
which all records <strong>of</strong> experiments and all observations are entered. Never rely on<br />
the memory in scientific work.
CHAPTBE I<br />
THE REPLACEMENT OF HYDROXYL AND HYDROGEN<br />
BY HALOGEN<br />
ALCOHOLS AND OLEFINES<br />
1. ETHYL BROMIDE FROM ETHYL ALCOHOL<br />
ALCOHOL (110 c.c. ; 90 g. <strong>of</strong> 95 per cent) is rapidly poured with<br />
continuous shaking but without cooling into a round-bottomed flask<br />
(capacity about 1 1.) containing 200 g. (110 c.c.) <strong>of</strong> concentrated<br />
sulphuric acid ; the warm mixture is then cooled to room temperature,<br />
75 g. <strong>of</strong> ice-water are cautiously added with continued cooling,<br />
FIG. 46<br />
and finally 100 g. <strong>of</strong> finely powdered potassium bromide are dropped<br />
in. The reaction mixture is then heated on a small sand bath over<br />
a powerful flame so that a fairly rapid distillation takes place.<br />
Since the ethyl bromide has a low boiling point the longest condenser<br />
available is used along with an adapter or else a coil condenser<br />
(Kg. 46), and a really rapid current <strong>of</strong> water is passed through.<br />
Before the distillation is begun sufficient water is poured into the<br />
receiver to submerge the end <strong>of</strong> the adapter and a few pieces <strong>of</strong> ice<br />
93
94 EBPLACBMBNT OF HYDEOXYL BY HALOGEN<br />
are thrown in. When oily drops, which sink in the water, cease to<br />
pass over, the reaction is at an end. If the distillate tends to be<br />
sucked back into the condenser during the distillation, the receiver<br />
should be lowered so that the adapter dips only slightly into the<br />
liquid. This can also be brought about by turning the adapter sideways.<br />
When distillation is over the contents <strong>of</strong> the receiver are<br />
transferred to a suitable separating funnel, the ethyl bromide which<br />
forms the lower layer is run into a conical flask (capacity 250 c.c),<br />
and then the ethyl ether, which is also produced during the reaction,<br />
is extracted from the ethyl bromide with concentrated sulphuric<br />
acid. Since heat is liberated during this process and material would<br />
be lost by evaporation, the crude ethyl bromide is cooled in a<br />
freezing mixture and the sulphuric acid is added drop by drop from<br />
a funnel with shaking until a lower layer <strong>of</strong> the acid separates. The<br />
layers are again separated in a smaller funnel and the ethyl bromide,<br />
which has been dried by the sulphuric acid, is finally distilled into a<br />
receiver cooled in a freezing mixture. The distilling flask is heated<br />
in water in a porcelain pot or basin over a small burner. Between<br />
35° and 40° the ethyl bromide passes over, the bulk at 38°-39°.<br />
On account <strong>of</strong> the low boiling point care must be taken during<br />
the experiment that the preparation is never left for any length <strong>of</strong><br />
time in an open vessel. Moreover, the finished preparation which<br />
is to be used for further work (cf. ethylbenzene) should not be kept<br />
in a thin-walled flask, least <strong>of</strong> all in summer, but should be stored<br />
in a thick-walled reagent bottle. Yield, 70-80 g.<br />
In this case, as in all others, a calculation should be made at the<br />
conclusion <strong>of</strong> the experiment <strong>of</strong> the percentage <strong>of</strong> the theoretical<br />
yield which has been obtained, keeping in mind the following considerations.<br />
According to the chemical equation one mole <strong>of</strong><br />
alcohol (46) should be used for one mole <strong>of</strong> potassium bromide (119).<br />
Actually, however, in the case <strong>of</strong> organic reactions, which as a rule<br />
do not proceed quantitatively, one <strong>of</strong> the components is used in<br />
excess, in keeping with the law <strong>of</strong> mass action (pp. 142,143), and its<br />
choice is <strong>of</strong>ten determined by economic considerations. Thus, for<br />
example, 1 kg. <strong>of</strong> potassium bromide costs about 6s., and 1 kg. <strong>of</strong><br />
duty-free alcohol, Is. 2d. The price <strong>of</strong> a mole <strong>of</strong> KBr (119 x 6s.) is<br />
therefore to that <strong>of</strong> a mole <strong>of</strong> alcohol (95 per cent) (46 x Is. 2d.)<br />
approximately as 14: 1. From the economic standpoint it is<br />
therefore advisable to use the cheaper alcohol in excess in order that<br />
as much as possible <strong>of</strong> the dearer bromine compound may be con-
ETHYL IODIDE FKOM ETHYL ALCOHOL 95<br />
verted into ethyl bromide. The proportions used in the above<br />
experiment have been adapted to this consideration. Theoretically<br />
39 g. <strong>of</strong> alcohol are required for 100 g. <strong>of</strong> KBr, whilst actually 86 g.<br />
(90 g. <strong>of</strong> 95 per cent) are used, i.e. more than double the theoretical<br />
quantity. Hence when the theoretically possible yield is calculated<br />
here the amount <strong>of</strong> potassium bromide used must be taken as the<br />
basis <strong>of</strong> reckoning. If it is desired to convert an alcohol which is<br />
more valuable than KBr into its bromide, the inorganic substance<br />
would naturally be used in excess.<br />
The preparation is used for making diethyl eihylmalonate (p. 254).<br />
Methyl Bromide.—The simplest alkyl bromide is prepared in<br />
an esentially similar way (Bygden, J. pr. Chem., 1911, 83, 421).<br />
Since it boils at 4-5° it is difficult to keep in stock, but its direct<br />
application in the Grignaxd reaction, in place <strong>of</strong> the dearer iodine<br />
compound, is very much to be recommended. Uses analogous to<br />
those <strong>of</strong> ethyl bromide.<br />
2. ETHYL IODIDE FROM ETHYL ALCOHOL J<br />
Absolute alcohol (50 c.c.) is poured into a small flask (capacity<br />
about 200 c.c.) containing 5 g. <strong>of</strong> red phosphorous and then, during<br />
the course <strong>of</strong> a quarter <strong>of</strong> an hour, 50 g. <strong>of</strong> finely powdered iodine<br />
are gradually added with frequent shaking and occasional cooling<br />
by dipping the flask into cold water. An efficient water condenser<br />
is then attached to the flask, the mixture is left for two hours with<br />
frequent shaking and heated for two hours on the water bath under<br />
reflux. Then the ethyl iodide is distilled through a downward<br />
condenser, preferably with the flask dipping into the vigorously<br />
boiling water. If the last part <strong>of</strong> the material distils only with<br />
difficulty, the water bath is removed and the flask, after drying, is<br />
heated over a luminous flame which is kept in constant motion. The<br />
distillate, which is coloured brown by dissolved free iodine, is shaken<br />
in a separating funnel first with water (repeatedly) to remove the<br />
alcohol, then with a few drops <strong>of</strong> bisulphite solution to remove the<br />
iodine, and, finally, with an equal volume <strong>of</strong> sodium hydroxide solution.<br />
The colourless oil so obtained is drawn <strong>of</strong>f from the funnel,<br />
dried with a little granulated calcium chloride, and distilled directly<br />
over a small flame. If the calcium chloride should float on the ethyl<br />
1 F. Beilstein, Annalen, 1863, 126, 250.
96 EBPLACBMBNT OF HYDEOXYL BY HALOGEN<br />
iodide, pour the latter into the distilling flask through a funnel<br />
plugged with asbestos or glass wool. Ethyl iodide boils at 72°.<br />
Yield, about 50 g. What percentage <strong>of</strong> the theoretical is this ?<br />
Use in the synthesis <strong>of</strong> ethyl diethylmalonate and for Grignard<br />
reactions.<br />
Methyl iodide is prepared in a completely analogous manner.<br />
Boiling point 44°. Used like ethyl iodide.<br />
Remarks on 1 and 2.—These two reactions are special cases <strong>of</strong> a<br />
general change, namely, the substitution <strong>of</strong> an alcoholic hydroxyl<br />
group by a halogen atom. This substitution can be carried out in<br />
two ways ; first, as in the preparation <strong>of</strong> ethyl bromide, 1, by acting on<br />
alcohols with hydrogen halides, e.g.<br />
C2H5.| OH + H|Br = H2O + C2H5.Br,<br />
(HC1, HI)<br />
or, second, as in the preparation <strong>of</strong> ethyl iodide, 2, by treating alcohols<br />
with halogen compounds <strong>of</strong> phosphorus, e.g.<br />
3C2H5.OH + PI3 = 3C2H5.I + PO3H3<br />
(PCI3, PBr3).<br />
The first reaction proceeds most easily with hydrogen iodide since<br />
in many cases mere saturation with the gaseous acid suffices to bring<br />
it about. Hydrogen bromide reacts with greater difficulty, and in its<br />
case it is frequently necessary to heat the alcohol saturated with this<br />
acid in a sealed tube. The preparation <strong>of</strong> ethyl bromide described<br />
above, in which, the HBr is liberated from the potassium bromide by<br />
means <strong>of</strong> concentrated sulphuric acid, constitutes a very smooth<br />
example <strong>of</strong> this reaction.<br />
Hydrogen chloride reacts most difficultly, and here it is necessary<br />
(as, for example, in the preparation <strong>of</strong> methyl and ethyl chloride)<br />
to use a dehydrating agent, preferably zinc chloride, or, as in the case<br />
<strong>of</strong> the higher alcohols, to heat under pressure in a sealed vessel.<br />
Aromatic alcohols, e.g. benzyl alcohol, are thus esterified by concentrated<br />
halogen acids more easily than the aliphatic.<br />
The reaction cannot be extended to phenols, however, but it can<br />
be applied to di- and polyhydric alcohols. Here the number <strong>of</strong> hydroxyl<br />
groups replaced depends on the experimental conditions, e.g. quantity <strong>of</strong><br />
halogen hydride, temperature, and so on, e.g.<br />
CH2.OH CH2.Br<br />
I +HBr = I +H2O,<br />
CH2.OH CH2.OH<br />
Ethylene glycol Ethylene bromohydrin
EBPLACBMBNT OF HYDKOXYL BY HALOGEN 97<br />
CH2.OH CH2.OH<br />
CH.OH + 2HC1 = CH.C1 +2H2O .<br />
CH2.OH CH2.C1<br />
Glycerol Dichlorohydrin<br />
Hydrogen iodide not only esterifies polyhydric alcohols but also<br />
reduces them. Thus glycerol passes by way <strong>of</strong> 1 : 2 : 3-triiodopropane<br />
into isopropyl iodide :<br />
CH2OH.CHOH.CH2OH + 3HI = CH2I.CHI.CH2I + 3H2O<br />
CH2I.CHI.CH2I + 2HI = CH3.CHI.CH3 + 2I2.<br />
Similarly the tetrahydric erythritol and the hexahydric mannitol<br />
are converted respectively into 2-iodobutane and 2-iodohexane. Formulate<br />
! Naturally the reaction also takes place with hydroxyacids.<br />
The second reaction proceeds much more energetically than the<br />
first, especially if preformed phosphorus halide is used. This is, however,<br />
not always necessary, at least not in the case <strong>of</strong> replacements by bromine<br />
and iodine ; in many cases the procedure is rather to produce the halide<br />
only during the reaction, either by dropping bromine from a separating<br />
funnel into a mixture <strong>of</strong> alcohol and red phosphorus or, as above, by<br />
adding finely powdered iodine. Like the former, this reaction can also<br />
be applied to polyhydric and to substituted alcohols; indeed, it is<br />
possible to replace all the OH groups by halogens, and in particular<br />
also by chlorine.<br />
In many cases the solid, more active and much less volatile pentachloride<br />
is used instead <strong>of</strong> phosphorus trichloride. Then it is necessary<br />
to use a whole mole <strong>of</strong> PC1S for each mole <strong>of</strong> alcohol since the reaction<br />
leads to the formation <strong>of</strong> the much more 'sluggish phosphorus oxychloride,<br />
e.g.<br />
CH3.CH2OH + PC15 = CH3.CH2C1 + POC13 + HC1.<br />
In recent years thionyl chloride has also been brought into use for<br />
the same reaction ; it has the advantage that its decomposition products<br />
are gaseous and hence do not interfere with the working up <strong>of</strong> the<br />
reaction mixture.<br />
C4H9.CH2OH + SOC12 = C4H9.CH2C1 + SO2 + HC1.<br />
Amyl alcohol Amyl chloride<br />
The more energetic action <strong>of</strong> the halide <strong>of</strong> phosphorus also shows<br />
itself in the fact that even the hydroxyl groups <strong>of</strong> phenols can be replaced<br />
by this reaction :<br />
C6H6.OH + PC15 = C6H5.C1 + POCI3 + HC1,<br />
Phenol (Br5) (Br) (Br,) (Br) .<br />
H
98 ALKYL HALIDBS<br />
The yields thus obtained are much less satisfactory since the phosphorus<br />
oxychloride, acting on unchanged phenol, produces esters <strong>of</strong><br />
phosphoric acid, e.g.<br />
POClg + 3C6H5.OH = PO(OC6H5)3 + 3HC1.<br />
The alkyl halides CBH2)!+1C1 (Br, I) are colourless and usually liquid;<br />
methyl chloride, methyl bromide, and also ethyl chloride, are gaseous<br />
at ordinary temperatures and the members <strong>of</strong> high molecular weight,<br />
such as cetyl iodide C16H22I, are semi-solid, paste-like masses.<br />
In addition to " methyl iodide " the term " iodomethane " can be<br />
used. For purposes <strong>of</strong> classification the alkyl halides are to be regarded<br />
as esters. The halogen does not ionize and its mobility increases in<br />
the order chloride, bromide, iodide.<br />
As esters the alkyl halides are hydrolysed by alkalis to alcohols and<br />
salts <strong>of</strong> halogen acids. They are converted by nascent hydrogen into<br />
hydrocarbons, by ammonia into amines, by alkoxides into ethers, by<br />
alkali hydrogen sulphides into mercaptans, by potassium cyanide into<br />
nitriles, and by sodium acetate into acetic esters. (Formulate these<br />
reactions.) The alkyl halides are practically insoluble in water but are,<br />
on the other hand, miscible with organic solvents. As a consequence<br />
<strong>of</strong> the great affinity <strong>of</strong> iodine for silver, the alkyl iodides are almost<br />
instantaneously decomposed by aqueous-alcoholic silver nitrate solution,<br />
and so yield silver iodide and alcohol. The important method <strong>of</strong> Ziesel<br />
for the quantitative determination <strong>of</strong> alkyl groups combined in the form<br />
<strong>of</strong> ethers, depends on this property (cf. p. 80).<br />
Chlorine and bromine can be replaced by iodine by means <strong>of</strong> alkali<br />
iodide, and this is <strong>of</strong> importance in cases where direct treatment <strong>of</strong><br />
alcohols with hydriodic acid gives a bad yield or none at all, e.g. in the<br />
preparation <strong>of</strong> ethylene iodohydrin :<br />
CH2OH.CH2C1 + Nal = CH2OH.CH2I + NaCl.<br />
Since the reaction requires heat, it cannot be carried out in an<br />
aqueous medium for fear <strong>of</strong> hydrolysis; moreover, in most cases, the<br />
insolubility <strong>of</strong> the chloride in water precludes the use <strong>of</strong> this solvent.<br />
Following Finkelstein, acetone well dried with calcium chloride and<br />
anhydrous sodium iodide, which is rather soluble in acetone, are<br />
used.<br />
The iodo-compounds soon turn brown (iodine) on keeping, especially<br />
if exposed to light. In order to decolorise them again they are shaken<br />
with some mercury or finely divided silver.<br />
Since halogen hydride can be removed from the alkyl halides, this<br />
group is also directly connected with the defines :<br />
H3C.CH2Br ~ HB > H2C = CH2 + HBr .<br />
The removal is most suitably accomplished by means <strong>of</strong> alcoholic
EBPLACBMENT OF HYDKOXYL BY HALOGEN 99<br />
potassium Hydroxide solution. 1 In many cases tertiary bases are also<br />
used, such, as pyridine, quinoline, or dimethylaniline.<br />
Of the synthetic reactions <strong>of</strong> the alkyl halides that with potassium<br />
cyanide, which enabled H. Kolbe to synthesise acetic acid from a<br />
methane derivative, has already been mentioned (cf. the preparations<br />
on pp. 137 and 254). Of the simpler syntheses that <strong>of</strong> Wtirtz may be<br />
mentioned here. Metallic sodium removes the halogen from two<br />
molecules and the two radicles combine. Thus, in the simplest case,<br />
ethane is formed from methyl bromide :<br />
H3C.Br Br.CH3 —>• H3C.CH3 + 2NaBr .<br />
Na Na<br />
The reaction is applied preparatively to triphenylchloromethane,<br />
p. 346. Finally, the alkyl halides have also acquired extraordinary<br />
importance as starting materials for the Grignard reaction, discussed on<br />
pp. 337 ff.<br />
Fittig's synthesis 2 differs from that <strong>of</strong> Wtirtz in that in the former<br />
the sodium removes the halogen simultaneously from an aryl and an<br />
alkyl halide : e.g.<br />
C6H5Br + C2H5Br + 2Na —>• C6H5C2H5 + 2NaBr .<br />
Ethylbenzene<br />
It can be applied generally; homologous bromobenzenes such as<br />
dibromobenzene and all possible alkyl bromides come within its scope.<br />
The reaction takes place also, although less readily, between two<br />
molecules <strong>of</strong> aryl bromide :<br />
2 C6H5Br + 2Na —>• C6H5.C6H5 + 2NaBr .<br />
Diphenyl, however, is prepared by thermal dehydrogenation <strong>of</strong><br />
benzene. (A current <strong>of</strong> benzene vapour is passed through a red-hot<br />
iron tube.)<br />
The Fittig reaction does not proceed so simply as the above equations<br />
indicate. The work <strong>of</strong> Acree 3 and Schlubach 4 has shown that in the<br />
first phase <strong>of</strong> the reaction sodium compounds <strong>of</strong> the hydrocarbons are<br />
formed. These then react with the second molecule <strong>of</strong> the organic<br />
bromide and sodium bromide is eliminated :<br />
1. R.Br + 2Na —>• RNa + NaBr.<br />
2. RNa + BrR' —>• R—R' + NaBr.<br />
Since both R'Br and RBr react at first with sodium and since both<br />
1 This reagent is very much used and it is best to keep a stock. Dissolve 25 g.<br />
<strong>of</strong> potassium hydroxide sticks in 100 c.c. <strong>of</strong> methyl alcohol by warming or by leaving<br />
over night in the cold ; potassium hydroxide in ethyl alcohol soon resinifies. Remove<br />
carbonate by filtration and determine the KOH content by titration.<br />
a Tollens and Fittig, Annalen, 1864, 131, 303; cf. the preceding edition <strong>of</strong> this<br />
book, p. 107.<br />
3 Amer. Chem. J., 1903, 29, 588.<br />
1 Ber., 1922, 55, 2889; see also Schlenk, Ber., 1917, 50, 262.
100 EBPLACBMBNT OF HYDKOGEN BY CHLOKINE<br />
sodium compounds can react with RBr and R'Br in principle, three<br />
reactions, leading to the products R—R', R—R, and R'—R', are possible<br />
in Fittig's synthesis.<br />
Bromobenzene reacts more rapidly with sodium than does ethyl<br />
bromide, but sodium phenyl reacts more rapidly with ethyl bromide<br />
than with bromobenzene : hence the ready production <strong>of</strong> ethylbenzene<br />
in the example given.<br />
3. BENZYL CHLORIDE FROM TOLUENE 1<br />
The use <strong>of</strong> cork or rubber connections should be avoided when<br />
working with chlorine, bromine, or halogen acids. For the present<br />
preparation the flask 2 shown in Fig. 47, p. 104 (with inlet tube), is used.<br />
A short thermometer, the lower part <strong>of</strong> which rests in a support consisting<br />
<strong>of</strong> a glass tube 3—4 cm. long and constricted in the middle,<br />
is slipped into the flask, held horizontally. The end <strong>of</strong> the support<br />
which rests ori. the bottom <strong>of</strong> the flask is rounded in a flame so as to<br />
prevent scratching. Next pure toluene (100 g.)is poured into the flask<br />
and heated to boiling in the air bath. A rapid current <strong>of</strong> chlorine<br />
from a cylinder is now passed in through a wash-bottle with sulphuric<br />
acid and the ground-in inlet tube, until the temperature <strong>of</strong> the<br />
vigorously boiling liquid has reached 156°. In order that escaping<br />
chlorine may be rendered harmless the upper end <strong>of</strong> the condenser is<br />
connected by means <strong>of</strong> a tube, which should not dip into the liquid, to<br />
a vessel containing caustic alkali solution. Experience has shown<br />
that the time during which chlorine has to be passed in depends on<br />
the illumination 3 ; in bright sunlight the reaction is over in a few<br />
hours, whereas on dull days it occupies half a working day. As far<br />
as possible, therefore, advantage is taken <strong>of</strong> the light.<br />
Next, the contents <strong>of</strong> the flask are directly distilled in a vacuum.<br />
After a fraction consisting <strong>of</strong> unchanged toluene has passed over, the<br />
bulk <strong>of</strong> the distillate is collected over a range <strong>of</strong> 7° (at 12 mm. between<br />
63° and 70°). Pure benzyl chloride boils at 64°/12 mm. Yield 65-<br />
70 per cent <strong>of</strong> the theoretical.<br />
The preparation obtained by vacuum distillation is purer and<br />
keeps better than that distilled under atmospheric pressure, since<br />
in the latter case elimination <strong>of</strong> HC1 always occurs.<br />
1 Cannizzaro, Ann. Chim., 1855, [3] 45, 468; Beilstein and Geitner, Annalen,<br />
1866, 139, 332 ; Schramm, Ber., 1885, 18, 608.<br />
2 It should be obtainable on loan from the demonstrator.<br />
3 G. Book and J. Eggert, Z. EUUrochem., 1923, 29, 521; Ber., 1926, 59, 1192 ;<br />
F. Bergel, Ber., 1926, 59, 153.
BENZYL CHLOKIDE FKOM TOLUENE 101<br />
Uses : for benzyl cyanide (p. 137), ethyl benzylmalonate (p. 255),<br />
the Grignard reaction.<br />
The theoretically simplest method <strong>of</strong> replacing hydrogen united to<br />
carbon by halogen consists in acting on saturated hydrocarbons with<br />
free halogen. The process, like the reaction between chlorine and hydrogen,<br />
is catalytically accelerated by light and when applied to methane<br />
and chlorine leads to the conversion <strong>of</strong> this hydrocarbon into mono-,<br />
di-, tri-, and tetrachloromethane. The higher paraffins are also chlorinated<br />
in this way, but, as a preparative method, the process is inconvenient<br />
and has the disadvantage that various reaction products are<br />
produced simultaneously and are difficult to separate. As a general<br />
rule, the chlorine first attacks that carbon atom which is poorest in<br />
hydrogen. In the aliphatic series the alcohols, which are more easily<br />
obtainable in the pure state than the hydrocarbons, constitute the sole<br />
starting materials for the preparation <strong>of</strong> the halogen compounds<br />
(reactions 1 and 2). Substitution by chlorine is much simpler in the case<br />
<strong>of</strong> toluene and the homologous methylbenzenes (xylenes, etc.). Here<br />
we have two quite distinct processes.<br />
1. Substitution occurs exclusively in the ring when typical halogencarriers<br />
such as iron filings or iodine are used. From toluene the oand<br />
y-derivatives are produced together.<br />
2. In the absence <strong>of</strong> such a carrier the benzene ring is not attacked<br />
in the slightest, even at the boiling point. The rate <strong>of</strong> substitution in<br />
the methyl group (side chain), which is unmeasurably small in the cold,<br />
increases to an extent sufficient for preparative purposes, in accordance<br />
with the general law that each rise <strong>of</strong> 10° in the temperature produces a<br />
two to threefold increase in the velocity <strong>of</strong> the reaction. This reaction<br />
is sensitive to light, like all direct replacement <strong>of</strong> hydrogen by chlorine.<br />
The statement that addition <strong>of</strong> phosphorus pentachloride also accelerates<br />
the reaction is incorrect. The reaction between toluene and<br />
chlorine presents a very fine example <strong>of</strong> the specific influence <strong>of</strong> various<br />
catalysts on a reacting system.<br />
For preparative purposes it is <strong>of</strong> great importance that the entrance<br />
<strong>of</strong> the second chlorine atom into the side chain proceeds at a much<br />
lower rate than the first phase <strong>of</strong> the reaction. Hence almost all the<br />
chlorine is used up by the toluene present before any significant further<br />
chlorination <strong>of</strong> the benzyl chloride occurs. The proximity <strong>of</strong> the<br />
benzene ring makes the chlorine less firmly attached to the side chain,<br />
i.e. more mobile than in the true paraffins. In explanation it is suggested<br />
that the benzene ring uses up more <strong>of</strong> the combining energy <strong>of</strong> the<br />
methane carbon atom than does alkyl or hydrogen, and that therefore<br />
less is available for the chlorine. (Thiele and Werner's theory <strong>of</strong> the<br />
distribution <strong>of</strong> affinity.) From this example we learn that although<br />
the connecting lines in our formulae give formal expression to the<br />
quadrivalency <strong>of</strong> carbon, they tell us nothing about the energy relation-
102 EBPLACBMBNT OF HYDKOGEN BY CHLOKINE<br />
ships <strong>of</strong> tlie individual bonds. It is only through a command <strong>of</strong> the<br />
systematic principles that the chemist can acquire the insight and understanding<br />
which enable him to read more into the diagrammatic formulae<br />
than is indicated by the uniform links between the individual atoms.<br />
Benzyl chloride undergoes all the transformations <strong>of</strong> the alkyl<br />
halides. Hydrolysis with hot aqueous alkalis yields the corresponding<br />
alcohol, benzyl alcohol C6H5.CH2OH, a colourless liquid which boils at<br />
206°. (Chap. V. 4, p. 220.)<br />
When benzyl chloride is treated with ammonia under suitable conditions<br />
benzylamine, C6H5.CH2NH2, is obtained. It is a rather strong,<br />
liquid base which exhibits all the characteristics <strong>of</strong> the aliphatic amines<br />
and differs completely from the ring-substituted aminotoluenes (toluidines)<br />
which are isomeric with it.<br />
In general it may be said that all changes in the methyl group <strong>of</strong><br />
toluene and <strong>of</strong> compounds <strong>of</strong> analogous constitution take place in the<br />
same way as in purely aliphatic alkyl groups.<br />
Continued chlorination <strong>of</strong> toluene introduces a second and finally<br />
a third chlorine atom into the side chain.<br />
Benzylidene chloride, C6H5.CHC12, a colourless liquid which, like<br />
benzyl chloride, provokes tears, is the technical starting material for<br />
the preparation <strong>of</strong> benzaldehyde. Cf. Chap. V. 3, p. 209.<br />
Benzotrichloride (phenylchlor<strong>of</strong>orm), C6H5.CC13.<br />
The effect <strong>of</strong> the benzene ring on the combining power <strong>of</strong> the<br />
adjacent carbon atom here shows itself with special clarity. Whereas<br />
chlor<strong>of</strong>orm is rather resistant towards alkalis, benzotrichloride is<br />
hydrolysed by them with extraordinary ease ; all three chlorine atoms<br />
are removed and benzoic acid is produced. It would be wrong to think,<br />
however, that in this reaction all the chlorine is removed at the same<br />
time in accordance with the equation :<br />
/Cl NaOH /OH /OH<br />
C6H5.Cf Cl NaOH -> C6H5.C^-OH + 3NaCl •> C6H5.C< +H2O.<br />
\C1 NaOH \OH X><br />
All chemical reactions proceed in stages and usually by the interaction<br />
<strong>of</strong> two molecules (reactions <strong>of</strong> the second order or bimolecular<br />
reactions). Hence our reaction will take place in stages and should be<br />
formulated as follows :<br />
/Cl /OH +NaOH xO<br />
C6H5.Cf-Cl + Na0H —>• C6H8.C£-C1 + NaCl >• C6H5.C C6H5.C
BKOMOBENZENE 103<br />
The intermediate products I and II are hydrolysed much, more<br />
rapidly than benzotrichloride and therefore escape detection.<br />
As regards intermediate product I it should also be remarked that<br />
compounds <strong>of</strong> this type, containing hydroxyl and halogen attached to<br />
the same carbon atom, are not capable <strong>of</strong> existence, but immediately<br />
undergo the change<br />
/OH .<br />
>C=O + HC1.<br />
/ Na /<br />
Experiment.—Boil a few drops <strong>of</strong> benzyl chloride with (halogenfree)<br />
alcoholic potassium hydroxide solution for a few minutes in a<br />
test tube on the water bath. Then dilute with water, acidify with<br />
nitric acid, remove undissolved material by extraction with ether,<br />
and add a few drops <strong>of</strong> silver nitrate solution.<br />
No bromine ion is liberated when the analogous experiment is<br />
performed with bromobenzene (next preparation). Distinction between<br />
halogen in aliphatic and aromatic combination.<br />
Analysis <strong>of</strong> the Benzyl Chloride.—The quantitative determination<br />
<strong>of</strong> halogen in substances containing halogen in aliphatic combination<br />
is not carried out in a sealed tube by the Carius method (cf. p. 69),<br />
but by hydrolysis with standard alcoholic potassium hydroxide<br />
solution. Since this method is very <strong>of</strong>ten used, a check on the purity<br />
<strong>of</strong> the present preparation may be combined with practice in this<br />
method <strong>of</strong> analysis.<br />
In a small round-bottomed flask which has been frequently used<br />
and well steamed, an accurately weighed amount <strong>of</strong> benzyl chloride<br />
(about 1 g.) is boiled for one hour under reflux with one and a half<br />
times the calculated amount <strong>of</strong> approximately normal alcoholic<br />
sodium hydroxide solution; the solution is then diluted with two<br />
volumes <strong>of</strong> water, and the excess <strong>of</strong> alkali is titrated with 0-5 Nhydrochloric<br />
acid after addition <strong>of</strong> phenolphthalein.<br />
This method can naturally only be used when no other acids are<br />
formed. In that case the halogen is titrated with thiocyanate by<br />
Volhard's method.<br />
4. BROMOBENZENE<br />
A round-bottomed flask (capacity 500 c.c.) has a side tube, to<br />
which a condenser is attached by means <strong>of</strong> a ground joint, and a<br />
dropping funnel in the upright neck, also provided with a ground
104 EBPLACBMBNT OF HYDEOGBN BY BKOMINE<br />
joint (Fig. 47 ; corks and rubber stoppers are so seriously attacked<br />
by bromine that clean working without ground joints is made very<br />
difficult). The upper end <strong>of</strong> the condenser is connected by means <strong>of</strong><br />
a waxed cork to a large Peligot tube (Fig. 48), or to a conical flask,<br />
in which the hydrogen bromide produced is absorbed (in the latter<br />
case the delivery tube does not dip into the water).<br />
Benzene (90 c.c. ; 1 mole) and iron filings (2 g.) are poured into<br />
the flask and 53 c.c. (160 g.) <strong>of</strong> bromine are added little by little<br />
from the funnel with shaking. The beginning <strong>of</strong> the reaction and<br />
the accompanying evolution <strong>of</strong><br />
hydrogen bromide are awaited,<br />
and the addition <strong>of</strong> bromine is<br />
then so regulated that the reaction<br />
FIG. 47 FIG. 48<br />
proceeds briskly without becoming violent. If, towards the end,<br />
the substitution becomes too sluggish, the flask is heated for a short<br />
time on the water bath until all the bromine is consumed. The<br />
reaction mixture is then transferred to a larger round-bottomed<br />
flask and distilled with steam. As soon as crystals <strong>of</strong> ^i-dibromobenzene<br />
appear in the condenser the receiver is changed and this byproduct<br />
is then driven over completely.<br />
The monobromobenzene, which came over first, is allowed to<br />
settle in a separating funnel, drawn <strong>of</strong>f, dried for one hour with<br />
calcium chloride, and then distilled. When the bulk <strong>of</strong> the fraction<br />
which passes over between 140° and 170° is redistilled it yields a<br />
distillate which mainly boils between 152° and 158° and consists <strong>of</strong><br />
fairly pure bromobenzene. The material must be distilled again<br />
within narrower boiling point limits if it is to be used for the
BKOMOBENZENE 105<br />
Grignard reaction described later (p. 337). Yield 70-80 g. The<br />
pure compound boils at 155°.<br />
p-Dibromobenzene.—The residue which remains in the flask at<br />
the first distillation is poured while still hot into a small porcelain<br />
basin, and after it has solidified it is freed from oily matter on a<br />
porous plate ; the product from the steam distillation is dried in<br />
the same way.<br />
In this operation and in all similar ones the substance should not be<br />
pressed down on the plate with, the spatula but laid on with gentle<br />
pressure, so that the capillary action <strong>of</strong> the plate exerts its full effect.<br />
In the case <strong>of</strong> very sticky substances the material is transferred after<br />
a few hours with the spatula to an unused part <strong>of</strong> the plate.<br />
After drying, the ^i-dibromobenzene is recrystallised from a little<br />
alcohol from which it separates in magnificent colourless prisms.<br />
Melting point 89°.<br />
Hydrobromic Acid as By-Product.—During the reaction 80 g. <strong>of</strong><br />
hydrogen bromide are formed ; about 200 c.c. <strong>of</strong> water are required<br />
for absorption. Therefore, if an insufficiently large receiver is used,<br />
its contents must be renewed as soon as fumes begin to appear.<br />
The hydrobromic acid is purified by distillation from a flask having<br />
a condenser slipped over the side tube (Fig- 19). After some water<br />
has passed over, the boiling point rises to 126°, and at this temperature<br />
48 per cent acid passes over. This material is very useful for all<br />
kinds <strong>of</strong> work in the laboratory. Thus, for example, the potassium<br />
bromide required for the preparation <strong>of</strong> the alkyl bromides can be<br />
prepared from it by transferring to a capacious vessel and adding<br />
the calculated amount <strong>of</strong> potassium carbonate until the neutral<br />
point is reached.<br />
A useful rule for operations <strong>of</strong> this kind : Set aside a small part <strong>of</strong><br />
the less accessible substance—here the hydrobromic acid—so that if<br />
the neutral point is accidentally passed no difficulty is experienced.<br />
Pure bromobenzene loses no bromine ions when boiled with potassium<br />
hydroxide solution. Check this.<br />
The halogen is very firmly fixed to the benzene nucleus; the aryl<br />
halides do not give the reactions characteristic <strong>of</strong> the alkyl halides.<br />
Only by hydrogen activated by a catalyst or by vigorous nascent<br />
hydrogen (sodium in alcohol) can the halogen be replaced, although the<br />
aryl halides also react with magnesium (Chap. IX. 1, p. 337), and the<br />
halogen is likewise removed in the Fittig synthesis (p. 99).<br />
If it is desired to compare bromobenzene with a halide <strong>of</strong> the aliphatic<br />
series, the saturated ethyl bromide must naturally not be chosen
106 THEOKY OF SUBSTITUTION IN BENZENE<br />
for comparison, but ratter substances <strong>of</strong> the type <strong>of</strong> vinyl bromide,<br />
H H<br />
H HC=CH2,<br />
H H ^ r<br />
i.e. substances which have the halogen attached to a doubly linked carbon<br />
atom. Then it is found that the halogen is also very firmly bound in<br />
halogenated olefines <strong>of</strong> this type, so that no fundamental difference<br />
exists between them and the halogen substitution products <strong>of</strong> benzene.<br />
The reactivity <strong>of</strong> aromatically bound halogen is increased by nitrogroups<br />
in the ortho- and yam-positions ; likewise the chlorine in ochlorobenzoic<br />
acid is rather loosely held.<br />
How is the course <strong>of</strong> halogen substitution in the benzene nucleus to be<br />
explained ? It is not at all probable that direct replacement <strong>of</strong> hydrogen<br />
occurs, such as we must assume in the formation <strong>of</strong> benzyl chloride<br />
and in the reaction between methane and chlorine, since the hydrogen<br />
attached to the doubly bound carbon atom <strong>of</strong> olefines exhibits no special<br />
reactivity. However, various facts which will be considered later<br />
(p. 164) indicate that benzene reacts with halogen in fundamentally<br />
the same way as does ethylene. The behaviour <strong>of</strong> ethylene towards<br />
bromine is the subject <strong>of</strong> the next preparation.<br />
In the case <strong>of</strong> either substance the bromine is doubtless first added<br />
on at the double bond. Whilst the reaction takes place easily with the<br />
reactive double bond <strong>of</strong> the olefines, carriers such as iron, iron halide,<br />
and aluminium bromide are required for the sluggish double bond <strong>of</strong><br />
the benzene ring :<br />
H2C = CH2 DT % BrCH2 - CH2Br ; H<<br />
HBTHBr<br />
The ethylene addition product is saturated, that <strong>of</strong> benzene, on<br />
the other hand, is more unsaturated than is benzene itself, since the<br />
symmetrical cancelling <strong>of</strong> residual valency (Thiele) is upset and the<br />
" aromatic" character is destroyed. In order to re-establish this<br />
character it is only necessary for hydrogen bromide to be eliminated,<br />
which takes place with liberation <strong>of</strong> energy. The elimination occurs<br />
with extraordinary speed, even before the other double bonds, which<br />
have become reactive, have time to take up bromine.<br />
H H H H<br />
H —>• H/ \H + HBr.<br />
Br Br H<br />
In direct sunlight three molecules <strong>of</strong> chlorine or bromine add themselves<br />
to the three double bonds <strong>of</strong> benzene to form hexachlorocyclphexane<br />
or hexabromocyclohexane (benzene hexachloride) :
PKEPAKATION OF AN OLEFINE 107<br />
HC1 HC1<br />
>HC1.<br />
ICJ~HC1<br />
Whereas in benzene and in its derivatives tlie six substituents lie<br />
in the same plane, namely, that <strong>of</strong> the ring, they are distributed in<br />
cyclohexane in two planes parallel to that <strong>of</strong> the ring. Hence there<br />
results a special type <strong>of</strong> spatial isomerism when two hydrogen atoms<br />
united to different carbon atoms are replaced. The isomerism is caused<br />
by the position <strong>of</strong> the two substituents, for they may lie in the same<br />
plane (m-form), or one in each plane (irons-form). The phenomenon<br />
is closely related to the cis-trans isomerism <strong>of</strong> the ethylenes, <strong>of</strong> which the<br />
best-known example is that <strong>of</strong> maleic and fumaric acids.<br />
Thus two stereo-isomeric forms <strong>of</strong> 1 : 4-dihydroxycyclohexane<br />
(quinitol) are known :<br />
H(\ HaH2 QH H H2<br />
H2 H2<br />
H2<br />
H TT -11 11U XT XT xi<br />
2 £±2 "-2 "-2<br />
cis-Quinitol
108 BTHYLBNB FKOM ETHYL ALCOHOL<br />
<strong>of</strong> 190 c.c. (150 g.) <strong>of</strong> alcohol and 170 c.c. (300 g.) <strong>of</strong> concentrated<br />
sulphuric acid.<br />
As soon as vigorous evolution <strong>of</strong> ethylene has set in the alcoholsulphuric<br />
acid mixture is dropped in at such a rate that no copious<br />
frothing occurs and a regular current <strong>of</strong> ethylene is evolved. The<br />
temperature is kept continually under control (small flame !).<br />
In order to remove alcohol and ether the gas is passed through<br />
a wash-bottle containing concentrated sulphuric acid, 1 and sulphurous<br />
acid is removed in a three-necked wash-bottle 2 containing<br />
42V-sodium hydroxide and provided with a safety tube (Fig. 50).<br />
The gas then passes into two moderately wide<br />
wash-bottles each containing 25 c.c. <strong>of</strong> bromine ;<br />
in order to reduce loss by evaporation the bromine<br />
is covered with a layer <strong>of</strong> water 1 cm. deep and<br />
the two bottles are kept cool in a vessel <strong>of</strong> cold<br />
water. If the pressure permits, the last receiver<br />
in the train is a Peligot tube (Fig. 48, p. 104)<br />
FIG. 49 FIG. 50<br />
containing 2 iV-sodium hydroxide solution; if not, the bromine<br />
vapour which escapes is absorbed in sodium hydroxide solution<br />
in a corked conical flask (notch the side <strong>of</strong> the cork !) in which the<br />
delivery tube is above the surface <strong>of</strong> the liquid (shake from time to<br />
time !). The first two wash-bottles are conveniently closed with<br />
rubber stoppers. As soon as the bromine has been decolorised or,<br />
at least, as soon as bromine vapour is no longer visible over the<br />
brownish-red reaction product (in normal circumstances after two<br />
to three hours) the flask is disconnected from the receivers. Then<br />
1 Since ethylene combines with hot sulphuric acid to form ethylsulphuric acid,<br />
it may be necessary to cool this wash-bottle.<br />
2 Notice that during the evolution <strong>of</strong> the gas the sodium hydroxide solution<br />
must rise in the middle safety tube to about 20-30 cm. above the inner level. Why ?
PKEPAKATION OF AN OLEFINE 109<br />
the crude ethylene dibromide is shaken in a separating funnel with<br />
water and sodium hydroxide solution until decolorised and washed<br />
repeatedly with water. After drying with calcium chloride it is<br />
completely purified by distillation. Boiling point 130°. Yield<br />
125-150 g. Used in the preparation <strong>of</strong> glycol (p. 114) and also as a<br />
solvent.<br />
The use <strong>of</strong> highly concentrated phosphoric acid obviates the very<br />
troublesome frothing which occasionally occurs and is to be attributed<br />
to the oxidising action <strong>of</strong> the sulphuric acid. Only by cautious<br />
heating can the frothing otherwise be kept within bounds. Commercial<br />
syrupy phosphoric acid (150 g.) is dehydrated by heating<br />
slowly to 220° in a porcelain basin with constant stirring. The<br />
ethylene is produced in a small flask set up according to the directions<br />
given; the alcohol is added drop by drop from the funnel to<br />
the acid, which is poured in while cold and then heated to 210°-220°.<br />
The funnel is filled with alcohol beforehand. In order to absorb<br />
alcohol vapour it is sufficient to introduce into the train one washbottle,<br />
containing a saturated aqueous solution <strong>of</strong> calcium chloride<br />
and cooled in ice. In this case the amount <strong>of</strong> alcohol required is<br />
considerably smaller.<br />
Calculate how much alcohol is required to yield the amount <strong>of</strong><br />
ethylene necessary to decolorise the bromine.<br />
What volume does this amount <strong>of</strong> ethylene occupy ?<br />
If the ethylene produced with sulphuric acid is analysed<br />
(method ?) it is found that very much carbon monoxide is present.<br />
The phosphoric acid method is better suited for the production <strong>of</strong><br />
the pure gas, but the best way is to remove with zinc dust and<br />
glacial acetic acid the bromine from the ethylene dibromide already<br />
prepared. The dibromide is dropped into a suspension <strong>of</strong> an excess<br />
(not too great) <strong>of</strong> zinc dust in alcohol and glacial acetic acid (2-5<br />
moles) and the ethylene is collected over water in a gas-holder.<br />
The intramolecular elimination <strong>of</strong> water from alcohols, which<br />
constitutes the usual method for the preparation <strong>of</strong> defines, does not<br />
proceed so simply, when concentrated acids are used, as the equation<br />
CH3—CH2OH —>• CH2=CH2 + H2O<br />
would suggest. Already on gentle warming alcohol is esterified by<br />
concentrated sulphuric acid and yields ethylsulphuric acid. It is from<br />
the decomposition <strong>of</strong> the latter that the ethylene arises.<br />
CH3.CH2OH H ' so >' CH3.CH2.O.SO3H —> CH2:CH2
110 BTHYLBNB FKOM ETHYL ALCOHOL<br />
It will be remembered that the ethylsulphuric acid first formed<br />
is decomposed when hot (130°) by excess <strong>of</strong> alcohol and in this way<br />
ether is prepared.<br />
CH3.CH2.O.SO3H + HO.CH2.CH3 —> CH3.CH2.O.CH2.CH3<br />
+ H2SO4.<br />
Ethyl ether is also formed as a by-product during the preparation<br />
<strong>of</strong> ethylene.<br />
Bthylene, the " oil-forming gas ", was prepared already in 1795<br />
from spirits <strong>of</strong> wine and oil <strong>of</strong> vitriol by the five Dutch chemists,<br />
Deiman, Troostwyk, Bondt, Louwerenburgh, and Crells.<br />
Technically, ethylene is obtained from alcohol by catalytic removal<br />
<strong>of</strong> water with alumina heated to 200°-300° (Senderens). The alcohol<br />
vapour is led over the hot material. 1 For the preparative application<br />
<strong>of</strong> such reactions aluminium phosphate is as suitable as alumina.<br />
Instead <strong>of</strong> the acid sulphuric ester <strong>of</strong> the alcohol, as in our example,<br />
the ester <strong>of</strong> another acid, e.g. benzoic, is <strong>of</strong>ten submitted to thermal<br />
decomposition, and so the charring action <strong>of</strong> the sulphuric acid is<br />
avoided.<br />
Potassium bisulphate and anhydrous boric or oxalic acid are also used<br />
(acrolein from glycerol, pyruvic acid from tartaric acid). Tschugaev's<br />
xanthate method belongs to this class <strong>of</strong> reactions also.<br />
The chemical characteristics <strong>of</strong> the defines depend on their double<br />
bond, which can take part in a great variety <strong>of</strong> additive reactions.<br />
The following substances are added :<br />
1. Halogens, chlorine and bromine with especial ease, yielding<br />
dihalides.<br />
2. Hydrogen Halides to give alkyl halides. For preparative purposes<br />
hydrobromic acid dissolved in glacial acetic acid is generally used,<br />
and since the reaction proceeds slowly, the components are heated in a<br />
sealed tube.<br />
3. Sulphuric Acid (cf. supra) and other acids, e.g. acetic acid (technical<br />
application in the terpene group).<br />
4. Nitric Acid.—In the presence <strong>of</strong> concentrated sulphuric acid<br />
ethylene yields the nitric ester <strong>of</strong> nitroethyl alcohol.<br />
CH2:CH2 —^- CH2.CH2 —^- CH2.CH2<br />
NO2 OH NO2 O.NO2'<br />
5. Hypochlorous Acid according to the equation :<br />
CH2:CH2 J 10 ^ CH2—CH2<br />
Cl OH '<br />
1 Directions suitable for laboratory experiments are given by W. Kesting,<br />
Z. angew. Chem., 1925, 38, 362.
EBACTIONS OF OLEFINES 111<br />
Thus ethylene chlorhydrin is obtained by passing ethylene and<br />
carbon dioxide together into bleaching powder solution.<br />
6. Nitrogen Peroxide, to form dinitroethanes :<br />
R.CH:CH.R —> R.CH.CH.R<br />
NO,NC TO,<br />
With nitrogen trioxide N2O3 is added and the bimolecular pseudonitrosites<br />
are formed.<br />
7. Ozone (Harries, Staudinger) :<br />
Oxd^O-tLg 4~ Oo ^» ^^<br />
0 0<br />
Since the ozonides are decomposed on heating with water, in accordance<br />
with the equation<br />
/ ° \<br />
R.HC CH.R _ H -i^R.CHO + R.<br />
they provide a means <strong>of</strong> synthesising aldehydes (or ketones). The<br />
hydrolysis takes place at the ether linkage and dihydroxyalkyl peroxides<br />
RH(OH)C.O—O.C(OH)HR are formed as intermediate compounds (see<br />
also p. 205). These latter further decompose into aldehyde (or ketone)<br />
and hydrogen peroxide (Rieche). Benzene adds three molecules <strong>of</strong><br />
ozone, and the triozonide (ozobenzene) C6H609 is decomposed by water<br />
into three molecules <strong>of</strong> glyoxal. The ozonides are more smoothly<br />
decomposed by hydrogenaiion and no side reactions occur. Aldehyde or<br />
ketone is produced, an unstable hydroxyalkyl ether<br />
R_C—0 C—R<br />
H OH HO H<br />
being produced as intermediate product. Compare the production <strong>of</strong><br />
adipic aldehyde from cyclohexene (p. 384).<br />
8. Hydrogen.—The defines cannot be hydrogenated with nascent<br />
hydrogen from any <strong>of</strong> the usual reducing agents. The reduction<br />
only succeeds catalytically with hydrogen in the presence <strong>of</strong> finely<br />
divided metals, such as nickel (Sabatier), palladium (Paal, Skita), or<br />
platinum (Fokin, Willstatter). Cf. the preparations on pp. 376 ff.<br />
9. Perbenzoic Acid. (Prileschaiev's reaction). Alkylene oxides are<br />
formed.
112 EEACTIONS OF OLEFINES<br />
O.OH<br />
R.CH:CH.R + C6H5.C:O —> R.CH.CH.R + C6H5.COOH .<br />
10. Hydroxyl.—At low temperature the defines are converted into<br />
their glycols by permanganate :<br />
R.CH:CH.R —^ R.CHOH.CHOH.R .<br />
This oxidising agent, however, readily breaks the double bond, and<br />
the carbon atoms which it joined are oxidised further.<br />
If they are also united to hydrogen, carboxylic acids are formed,<br />
otherwise ketones.<br />
/CH3<br />
.CH3<br />
R.CH:CX —> R.COOH + OC<<br />
\CH,<br />
The reaction with permanganate constitutes a valuable and muchused<br />
test for unsaturation in an organic compound. The substance<br />
is dissolved in cold alcohol, a few drops <strong>of</strong> sodium carbonate solution<br />
are added, and then a drop.<strong>of</strong> dilute permanganate solution. Rapid<br />
disappearance <strong>of</strong> the red colour indicates the presence <strong>of</strong> a double<br />
bond. The " Baeyer test " can also be carried out in pure glacial<br />
acetic acid, which is stable towards permanganate. Another method<br />
<strong>of</strong> detecting double bonds is by the decolorisation <strong>of</strong> bromine. As a<br />
rule, chlor<strong>of</strong>orm is used as solvent.<br />
In regard to the rate at which the above-mentioned addition reactions<br />
proceed, the defines exhibit very great differences, depending<br />
on the nature <strong>of</strong> the molecule. When a double bond is shown in a<br />
formula it does not necessarily .follow that it is also capable <strong>of</strong> all the<br />
above transformations. Thus, for example, it is quite impossible to<br />
add bromine to tetraphe'nyleihylene (C6H5)2C:C(C6H5)2. The affinity <strong>of</strong><br />
the double bond, therefore, differs from case to case.<br />
If two double bonds are adjacent they can react as a closed system<br />
in additive reactions. Thus butadiene adds on bromine partly in the<br />
manner shown in the following equation :<br />
CH2=CH.CH=CH2 Br '> BrCH2.CH=CH.CH2Br.<br />
Its dicarboxylic acid, muconic acid, yields the /?y-unsaturated<br />
dihydromuconic acid on .reduction :<br />
HOOC.CH=CH.CH=CH.COOH—>• HOOC.CH2.CH=CH.CHa.COOH.<br />
In both cases the two original double bonds disappear and a new<br />
one appears between them; addition has taken place in the 1 : 4positions.<br />
The principle <strong>of</strong> 1 : 4-addition has found a particularly interesting
DIBNB SYNTHESIS' OF DIBLS 113<br />
and, from the standpoint <strong>of</strong> preparative work, important application<br />
in the " diene synthesis " discovered by Diels and Alder. 1 In this synthesis<br />
butadiene and numerous butadiene derivatives (isoprene, cyclopentadiene)<br />
add themselves to the single carbon bond yielding derivatives<br />
<strong>of</strong> tetrahydrobenzene. Thus from butadiene and maleic anhydride<br />
tetrahydrophthalic add is formed :<br />
• -CH X!0<br />
CH CH ^X CH CH—CO2H<br />
I + I 0 —> II I<br />
CH CH / CH CH—CO2H<br />
\ \ / \ /<br />
CH2 CO CH2<br />
A compound <strong>of</strong> the naphtfialene series is produced when butadiene is<br />
added to quinone :<br />
CH2 CO ,CH2\ /C0\<br />
/" / \ / \ H / \<br />
CH CH CH CH C CH<br />
I + II I —• II<br />
CH CH CH CH<br />
CH<br />
STT<br />
^±12<br />
When the " diene " used is cyclopentadiene, endo-cyclic ring systems<br />
result such as are also produced by vegetable cells in camphor and other<br />
terpenes.<br />
CH nTT/~i CH<br />
CH £ \ \ CH CH CH—CHO<br />
I CH2 + || -+ ||<br />
CH / CH2 CH<br />
CH CH<br />
The student is recommended to carry out the Diels and Alder diene<br />
synthesis when making preparations from the original literature. For<br />
example, he should condense cyclo-hexadiene with quinone (Annalen.<br />
1933, 507, 288) or furane with maleic anhydride (Ber., 1929, 62, 554).<br />
According to Thiele, the explanation <strong>of</strong> the phenomenon <strong>of</strong> 1 : 4addition<br />
is that the fields <strong>of</strong> force, which surround the carbon atoms<br />
separated by double* bonds, partially cancel each other between C2 and<br />
C3 because <strong>of</strong> the proximity <strong>of</strong> these atoms in space, so that a higher<br />
chemical potential exists at Cx and C4 than at C2 and C3. Consequently<br />
the places at which addition occurs preferentially are C1 and C4.<br />
1 Annalen, 1928, 460, 98; see also Z. angew. Chem., 1929, 42, 911.<br />
I
114 PAETIAL VALENCIES<br />
Applied to benzene this conception provides for a structure which<br />
is much more saturated than that possible in defines with several<br />
double bonds. In benzene the points <strong>of</strong> attack, which are always present<br />
m the open chain, are lacking :<br />
H H /?\.<br />
H , C = C — C = C H ,<br />
I f , w i t h T h i e l e , w e i n d i c a t e t h e m a c t i v a t i o n o f a d j a c e n t c a r b o n<br />
a t o m s b y a b r a c k e t , a s s h o w n a b o v e , w e s e e t h a t m b e n z e n e a l l t h e<br />
" p a r t i a l v a l e n c i e s ' ' c a n c e l o u t .<br />
T h i s p i c t u r e o f t h e b e n z e n e s t r u c t u r e , w h i c h t h u s r e s u l t s f r o m<br />
T h i e l e ' s c o n c e p t i o n s , s e e m s s t i l l t o - d a y t h e m o s t s u i t a b l e f o r d e d u c i n g<br />
a n d u n d e r s t a n d i n g t h e " a r o m a t i c " c h a r a c t e r o f b e n z e n e m r e l a t i o n<br />
t o t h e n a t u r e o f t h e d e f i n e s .<br />
W e b e l i e v e , h o w e v e r , t h a t t h e c o n c e p t o f " m a c t i v a t i o n " o f t h e<br />
p a r t i a l v a l e n c i e s s h o u l d b e r e p l a c e d b y t h a t o f t h e i r e n f e e b l e m e n t F o r ,<br />
i n t h e first p l a c e , b y n o m e a n s a l l s u b s t a n c e s w h i c h a d d t h e m s e l v e s t o<br />
s y s t e m s o f a d j a c e n t ( " c o n j u g a t e d " ) d o u b l e b o n d s d o s o m t h e 1 : 4 -<br />
p o s i t i o n s , a n d s e c o n d l y , b e n z e n e a c t u a l l y d o e s e x h i b i t t h e t y p i c a l b e -<br />
h a v i o u r o f a s u b s t a n c e w i t h t h r e e d o u b l e b o n d s , s i n c e i t d i r e c t l y a d d s ,<br />
f o r e x a m p l e , h a l o g e n , h y d r o g e n c a t a l y t i c a l l y a c t i v a t e d ( t o g i v e c y c l o -<br />
h e x a n e ) , o z o n e , a n d d i a z o a c e t i c e s t e r ( p . 2 8 1 ) , a l b e i t m o r e s l o w l y t h a n<br />
a n d e f i n e d o e s I t i s j u s t t h i s a d o p t i o n o f T h i e l e ' s h y p o t h e s i s i n<br />
a n a t t e n u a t e d d e g r e e w h i c h s e e m s t o r e n d e r t h e l o w e r v e l o c i t y o f<br />
t h e a d d i t i o n r e a c t i o n s o f b e n z e n e c o m p r e h e n s i b l e U n e x p e c t e d l y , t h e<br />
h i g h e r r i n g h o m o l o g u e o f b e n z e n e , t h e h y d r o c a r b o n c y c l o - o c t a t e t r a e n e<br />
( W i l l s t a t t e r a n d W a s e r ) , i s b y n o m e a n s t h e c h e m i c a l a n a l o g u e o f<br />
b e n z e n e I t i s y e l l o w , a n d e x h i b i t s t h e g r e a t r e a c t i v i t y o f a n d e f i n e<br />
w i t h f o u r d o u b l e b o n d s :<br />
C H C H C H<br />
C H C H<br />
C H C H C H<br />
T h e h i g h e r c o n j u g a t e d u n s a t u r a t e d s y s t e m s w i l l b e m e n t i o n e d<br />
l a t e r m c o n n e x i o n w i t h t h e p o l y e n e s a n d t h e c a r o t e n o i d s ( p . 2 3 3 )<br />
6 G L Y C O L ( E T H Y L E N E G L Y C O L ) F R O M E T H Y L E N E<br />
D I B R O M I D E 1<br />
G l y c o l d i a c e t a t e . — A m i x t u r e o f 6 3 g . ( 0 - 3 3 m o l e ) o f e t h y l e n e<br />
d i b r o m i d e , 2 0 g o f g l a c i a l a c e t i c a c i d , a n d 6 0 g . o f f r e s h l y f u s e d a n d<br />
1 H e n r y , B u l l S o c C h i m , 1 8 9 7 , [ m ] , 1 7 , 2 0 7 , C h e m Z e n t r . , 1 9 0 7 , I , 1 3 1 4<br />
! ) •
GLYCOL FKOM BTHYLBNB DIBKOMIDE 115<br />
finely powdered potassium acetate (cf. p. 127) is placed in a shortnecked,<br />
round-bottomed flask (capacity 0-5 1.) provided with a reflux<br />
condenser and is vigorously boiled for two hours on a sand bath<br />
or wire gauze over a large flame. The flask is then connected by<br />
means <strong>of</strong> a bent tube with a downward condenser and the reaction<br />
product is distilled over by means <strong>of</strong> a large luminous flame, which<br />
is kept in constant motion and is made progressively less luminous<br />
towards the end <strong>of</strong> the distillation. The distillate is then mixed<br />
with a further 60 g. <strong>of</strong> ethylene dibromide and 80 g. <strong>of</strong> potassium<br />
acetate ; the mixture is vigorously boiled for two to three hours on a<br />
sand bath as described above and is again distilled. By means <strong>of</strong> a<br />
Hempel column <strong>of</strong> about 10 cm. length the distillate is fractionated<br />
and the following fractions are collected separately : 1. Up to 140°,<br />
2. 140°-175°, 3. 175° to completion. Fractions 2 and 3 are then redistilled<br />
separately, when pure glycoldiacetate passes over between<br />
180° and 190° (the bulk at 186°). Yield about 70 g.<br />
If it is desired to improve the yield, the portions which pass over<br />
below 180° are heated once again for three hours with an equal weight<br />
<strong>of</strong> potassium acetate and are then treated as above described. In this<br />
way the yield is increased by another 15 g.<br />
Glycol.—In order to obtain free glycol from the ester, the latter<br />
is " transesterified " by boiling with a solution <strong>of</strong> hydrogen chloride<br />
in absolute methyl alcohol. This solution is prepared by passing<br />
hydrogen chloride into cooled absolute methyl alcohol, while excluding<br />
moisture, until the concentration is about 3 per cent, as<br />
indicated by the increase in weight on a balance sensitive to 0-1 g.;<br />
if too much hydrogen chloride has been passed in, more alcohol is<br />
added.<br />
Glycoldiacetate (49 g. =0-33 mole) is boiled under reflux in a<br />
200 c.c. round-bottomed flask with 60 c.c. <strong>of</strong> the hydrogen chloride<br />
solution for half an hour and then the methyl acetate and part <strong>of</strong><br />
the methyl alcohol are removed by distillation (slowly at first)<br />
through a downward condenser, the rest directly in vacuo at about<br />
50°. In order to separate small quantities <strong>of</strong> unchanged ester from<br />
the glycol remaining in the flask, the latter is closed by a rubber<br />
stopper, and the contents are shaken with 50 c.c. <strong>of</strong> absolute ether,<br />
in which glycol is insoluble. Adherent ether is then removed on a<br />
boiling water bath and the hot glycol is poured into a small distilling<br />
flask, fitted with an air condenser, and distilled. The main portion
116 GLYCOL FKOM BTHYLBNB DIBKOMIDE<br />
passes over at 195°. Yield 17-18 g. (80-90 per cent <strong>of</strong> the theoretical).<br />
Ethylene dibromide can also be converted into glycol by direct<br />
hydrolysis with dilute alkali carbonate solution; since, however, the<br />
reaction proceeds very slowly (in the heterogeneous system), and since,<br />
moreover, large amounts <strong>of</strong> water have to be evaporated, the indirect<br />
method here adopted is to be preferred ; it has the further advantage <strong>of</strong><br />
teaching two new reactions. This method—much used for converting<br />
an alkyl halide into the corresponding alcohol—consists in first transforming<br />
it into the acetic ester by means <strong>of</strong> potassium acetate (<strong>of</strong>ten<br />
also by silver acetate); this ester is then hydrolysed, usually in the<br />
ordinary way by means <strong>of</strong> aqueous alkali or mineral acid. In the<br />
present case, where water-soluble glycol is the end product, we do not,<br />
however, wish to forego the advantage <strong>of</strong> working in organic solvents,<br />
so that we remove the acyl group from the ester by esterifying it with<br />
another alcohol. The acid indeed distributes itself between the two<br />
alcohols, glycol and methyl alcohol, but mass action favours the latter,<br />
which is present in large excess. Hydrolysis <strong>of</strong> this type may be<br />
called trans-esterification. Further details about the formation and<br />
hydrolysis <strong>of</strong> esters will be found on p. 141 et seq.<br />
The reactions <strong>of</strong> the simplest dihydric alcohols, the 1 : 2-glycols,<br />
may be illustrated by means <strong>of</strong> the initial member <strong>of</strong> the series.<br />
When heated with sulphuric acid glycol loses water and yields<br />
acetaldehyde.<br />
Concentrated hydrochloric acid forms ethylene chlorhydnn; the<br />
second OH-group is replaced by chlorine with much greater difficulty :<br />
CH2OH.CH2OH HC '> CH2OH.CH2C1 + H2O.<br />
On a large scale ethylene chlorhydrin is prepared by the addition <strong>of</strong><br />
hypochlorous acid to ethylene, by passing CO2 and ethylene simultaneously<br />
into a solution <strong>of</strong> bleaching powder. Concentrated potassium<br />
hydroxide solution converts chloroethyl alcohol into ethylene oxide, by<br />
removal <strong>of</strong> HC1:<br />
CH,OH.CH,C1 —> CH,—CH,<br />
Special mention should be made <strong>of</strong> the ready conversion <strong>of</strong> the<br />
chlorhydrin, by means <strong>of</strong> tnmethylamine, to choline, a substance <strong>of</strong> great<br />
physiological importance. Choline chloride is obtained very easily<br />
when equimolecular amounts <strong>of</strong> the two components are made to<br />
interact for some time under the influence <strong>of</strong> heat; a concentrated<br />
solution <strong>of</strong> the amine in absolute alcohol is used.<br />
Glycols are dehydrogenated by lead tetra-acetate Pb (OCO CH3)4, the<br />
C—C bond being ruptured. From ethylene glycol two molecules <strong>of</strong>
ISOAMYL BTHBE 117<br />
formaldehyde are obtained. Pinacone is decomposed into two molecules<br />
<strong>of</strong> acetone by reversal <strong>of</strong> its method <strong>of</strong> formation x<br />
(H3C)2C C(CH3)2 ^ 2(H3C)2CO.<br />
OH HO<br />
Experiment.—Add three drops <strong>of</strong> glycol to a solution <strong>of</strong> 1 g. <strong>of</strong> lead<br />
tetra-acetate 2 in 40 c.c. <strong>of</strong> glacial acetic acid. After half an hour<br />
destroy excess <strong>of</strong> the oxidising agent with a little sulphurous acid,<br />
precipitate all the lead with sulphuric acid, filter <strong>of</strong>f the lead sulphate<br />
and test the filtrate for formaldehyde with fuchsine-sulphurous acid<br />
(see p. 214). The red solution becomes blue on adding concentrated<br />
hydrochloric acid (cf. p. 214).<br />
7. ISOAMYL ETHER 3<br />
A mixture <strong>of</strong> 500 g. <strong>of</strong> commercial amyl alcohol (fraction having<br />
b.p. 128°-132°) and 50 g. <strong>of</strong> concentrated sulphuric acid is heated to<br />
gentle boiling in a distilling flask having the side tube high up in the<br />
neck. Water and amyl alcohol distil over slowly and the temperature<br />
<strong>of</strong> the boiling mixture, as indicated on a thermometer which<br />
dips into the liquid, rises to 140° in the course <strong>of</strong> about eight to nine<br />
hours. Some time before this temperature is reached the amyl<br />
alcohol which has distilled is separated from the water in a separating<br />
funnel, dried for a short time over potassium carbonate and<br />
returned to the distilling flask. The contents <strong>of</strong> the flask are cooled<br />
to about 100° and distilled with steam ; the distillate separates into<br />
two layers. Using a column or, still better, a Widmer spiral (see<br />
p. 19) the oily layer is fractionally distilled. The crude amyl ether<br />
passes over in a yield <strong>of</strong> 200-230 g. at 168°-172°. For complete<br />
purification it is boiled in an oil bath for two hours under a reflux<br />
condenser with finely powdered sodamide (1-5 g. per 100 g. <strong>of</strong> ether)<br />
and is then separated from the sodamide by distillation. The<br />
distillate is shaken with dilute hydrochloric acid, dried over calcium<br />
chloride and then carefully distilled over sodium.<br />
1 R. Criegee, Ber., 1931, 64, 260; Annalen, 1930, 481, 263 ; 1933, 507, 159.<br />
2 Add 200 g. <strong>of</strong> red lead in portions to 750 c.c. <strong>of</strong> pure glacial acetic acid + 20 c.c.<br />
<strong>of</strong> acetic anhydride mechanically stirred and kept at 65°, adding each portion only<br />
after the red colour produced by the preceding portion has disappeared. The<br />
tetra-acetate crystallises out on cooling. It can be recrystallised from glacial<br />
acetic acid and is stable in the absence <strong>of</strong> moisture (O. Dimroth and R. Schweizer,<br />
Ber., 1923, 56, 1375). For the determination <strong>of</strong> lead tetra-acetate in solution, see<br />
R. Criegee, Ber., 1931, 64, 260.<br />
3 G. Schroeter and W. Sondag, Ber., 1908, 41, 1924.
118 CHLOKOACETIC ACID FKOM ACETIC ACID<br />
8. CHLOROACETIC ACID FROM ACETIC ACID AND CHLORINE 1<br />
Dry chlorine is led into a mixture <strong>of</strong> 150 g. <strong>of</strong> glacial acetic acid<br />
and 12 g. <strong>of</strong> red phosphorus contained inaflask (Fig. 47, p. 104), which<br />
is provided with a delivery tube and a reflux condenser and is heated<br />
on a vigorously boiling water bath. The flask should stand in a<br />
well-lit place, preferably in direct sunlight, since the rate <strong>of</strong> chlorination<br />
greatly depends on the illumination. As soon as a small portion<br />
<strong>of</strong> the mixture solidifies when cooled with ice-water and rubbed<br />
with a glass rod, the reaction is complete. In summer one day<br />
suflices, but on dull winter days the passing in <strong>of</strong> chlorine must be<br />
continued for a second day. To isolate the monochloroacetic acid<br />
the product <strong>of</strong> the reaction is fractionally distilled from a flask fitted<br />
with an air condenser ; the fraction which passes over at 150°-200°<br />
is separately collected in a beaker. The beaker is cooled with icewater<br />
while its contents are stirred with a glass rod and the portion<br />
which solidifies, consisting <strong>of</strong> pure monochloroacetic acid, is rapidly<br />
filtered at the pump ; the loose crystals are firmly compressed with<br />
a spatula or pestle. The filtration must not be continued too long<br />
or the chloroacetic acid will gradually be liquefied by the heat <strong>of</strong> the<br />
air. The filtrate is redistilled, the portion passing over between<br />
170° and 200° being separately collected. By repetition <strong>of</strong> the<br />
process just described (cooling and filtering) a second portion <strong>of</strong><br />
monochloroacetic acid is obtained. It is combined with the main<br />
portion and the whole is completely purified by a further distillation ;<br />
b.p. 186°, m.p. 63°, yield, variable : 80-125 g. Used for the preparation<br />
<strong>of</strong> nitromethane (p. 156), dieihyl malonate (p. 254), glyoine (p. 275),<br />
phenylglycine (p. 369).<br />
Since monochloroacetic acid, especially when warm, attacks the<br />
skin severely, care is indicated.<br />
The chlorination proceeds considerably more rapidly, and also in<br />
the absence <strong>of</strong> light, if 1 -5 g. <strong>of</strong> iodine, 7 g. <strong>of</strong> phosphorus pentachloride,<br />
and 3 g. <strong>of</strong> red phosphorus are added to the 150 g. <strong>of</strong> glacial acetic acid<br />
mentioned above. 2 When the reaction is over, the hot mixture is decanted<br />
from the phosphorus, diluted with 40 c.c. <strong>of</strong> glacial acetic acid,<br />
and cooled. The monochloroacetic acid which crystallises is rapidly<br />
filtered and washed with a little glacial acetic acid. In this way a<br />
pale red product results, which is freed from adherent iodine by standing<br />
in a desiccator over potassium hydroxide.<br />
1 R. H<strong>of</strong>fmann, Annalen, 1857, 102, 1; Russanow, Ber., 1892, 25, Ref. 334.<br />
2 H. Bruckner, Z. angew. Chem., 1927, 40, 973; 1928, 41, 226.
HALOGEN CAEEIBES 119<br />
The introduction <strong>of</strong> chlorine or bromine into a saturated chain is<br />
facilitated by the presence <strong>of</strong> a C:0-group. Thus, aldehydes and<br />
ketones are halogenated with great ease, the halogen entering exclusively<br />
in the a-position. It has been shown that in this process the<br />
enol-form, which is present in minute amounts, takes up bromine<br />
additively. 1<br />
CH3.C(OH):CH2 —>• CH3.COH.CH2Br —^ CH3.CO.CH2Br.<br />
Br<br />
Enol-form <strong>of</strong> acetone Intermediate product<br />
The intermediate product (which cannot be isolated) is then immediately<br />
converted into bromoacetone with elimination <strong>of</strong> HBr<br />
(Lapworth).<br />
The " loosening " influence <strong>of</strong> the carboxyl group on adjacent hydrogen<br />
is much smaller. Hence, in carboxylic acids substitution by<br />
halogen proceeds with much more difficulty but can be accelerated by<br />
illumination and by catalysts (carriers). The point <strong>of</strong> entry <strong>of</strong> the<br />
halogen is here also always at the carbon atom adjacent to the carboxyl<br />
group, the a-carbon atom.<br />
Iodine is suitable as a carrier in chlorinations since it combines<br />
with chlorine to form the reactive iodine monochloride, viz. :<br />
CH3.COOH + CII —> CH2C1.COOH + HI.<br />
Since the hydrogen iodide so formed is immediately reconverted<br />
by chlorine into iodine, iodine monochloride being then re-formed,<br />
we have here a good example <strong>of</strong> catalysis by a carrier readily interpreted<br />
from the chemical standpoint.<br />
The action <strong>of</strong> phosphorus is quite different and much more complicated.<br />
The phosphorus halide which is first formed reacts with the<br />
acid to form the acid chloride and this, with a second molecule <strong>of</strong> the<br />
acid, forms the anhydride :<br />
(a) CH3.COCI + HOOC.CH3 >• CH3.CO.O.CO.CH3 + HCI.<br />
Now, the anhydride is much more easily chlorinated (by substitution)<br />
than the acid and the intermediate product thus formed is ultimately<br />
hydrolysed by the hydrogen chloride produced in the process :<br />
CH2C1.COX<br />
CHgCl.COOH<br />
(b) >O + HC1 —>•<br />
H3C.CO/ CH3.COCI<br />
1 The pro<strong>of</strong> is based on the fact that the reaction between acetone and bromine<br />
is recognised as being unimolecular and not, as would be expected, bimolecular.<br />
In the determination <strong>of</strong> the velocity <strong>of</strong> reaction, therefore, the (slow) conversion<br />
<strong>of</strong> the ketone into the enol is measured, whilst the addition <strong>of</strong> the bromine occurs<br />
with immeasurable rapidity.
120 HALOGENATION<br />
The regenerated acetyl chloride can again take part in the reaction<br />
according to equation a.<br />
Although in the present case the amount <strong>of</strong> phosphorus used is<br />
small, equivalent amounts are <strong>of</strong>ten employed, particularly for the<br />
introduction <strong>of</strong> bromine, the acid bromide being produced and then<br />
substituted in the a-position. As a result, the reaction product is the<br />
bromide <strong>of</strong> the a-brominated acid which must be treated with water<br />
to convert it into the latter. Esters <strong>of</strong> the acid are <strong>of</strong>ten prepared from<br />
the acid bromide by the action <strong>of</strong> alcohols. (Hell-Volhard-Zelinsky<br />
process.)<br />
The a-halogenated carboxylic acids, <strong>of</strong> which the simplest is chloroacetic<br />
acid, are widely used in synthesis. Their conversion into<br />
hydroxy-acids (by hydrolytic elimination <strong>of</strong> the halogen) and into<br />
aminoacids (p. 275) may be mentioned here :<br />
C1CH2.COOH + HOH —>- HOCH2.COOH + HC1<br />
C1CH2.COOH + 2NH3 —>• H2N.CH2.COOH + NH4C1.<br />
The introduction <strong>of</strong> iodine is carried out according to the methods<br />
given on pp. 96, 97. j8-Halogenated carboxylic acids are obtained by<br />
the addition <strong>of</strong> hydrogen halides to a/2-unsaturated acids :<br />
CH2:CH.COOH HBr > CH2Br.CH2.COOH .<br />
Acrylic acid g-Bromopropionic acid
CHAPTBE II<br />
CARBOXYLIC ACIDS AND THEIR SIMPLE DERIVATIVES<br />
1. ACID CHLORIDES<br />
(a) ACETYL CHLORIDE 1<br />
PHOSPHORUS TRICHLORIDE (72 g.) is run from a dropping funnel into<br />
a distilling flask containing 90 g. (1-5 mole) <strong>of</strong> anhydrous glacial<br />
acetic acid and cooled in water. The flask is fitted with a downward<br />
condenser, and next warmed in a porcelain basin <strong>of</strong> moderate<br />
size containing water at 40°-50°, until the vigorous evolution <strong>of</strong><br />
hydrogen chloride slackens and the originally homogeneous liquid<br />
has separated into two layers. The acetyl chloride is then distilled<br />
from the lower layer <strong>of</strong> phosphorous acid by means <strong>of</strong> a vigorously<br />
boiling water bath. A small filter flask attached to the lower end<br />
<strong>of</strong> the condenser by a cork serves as a receiver and its contents are<br />
protected against atmospheric moisture by a calcium chloride tube<br />
connected by means <strong>of</strong> a rubber tube. The substance is purified by<br />
repeated distillation with the use <strong>of</strong> a thermometer. The fraction<br />
boiling between 48° and 53° is collected separately. (Boiling point<br />
<strong>of</strong> pure acetyl chloride 51°). Yield 70-80 g. Use in the preparation<br />
<strong>of</strong> acetic anhydride, see p. 126, and <strong>of</strong> acetophenone, p. 346.<br />
The product is tested for the presence <strong>of</strong> phosphorus (PC13) by decomposing<br />
a few drops with a little warm water and evaporating the<br />
solution in a porcelain capsule. The residue is twice evaporated with<br />
concentrated nitric acid or with bromine water and is finally tested<br />
for phosphoric acid in the usual way. If phosphorus is detected, the<br />
material should again be distilled with a few drops <strong>of</strong> glacial acetic acid.<br />
(6) BENZOYL CHLORIDE<br />
Into a round-bottomed flask (capacity 0-25 1.) fitted if possible<br />
with a ground-in condenser and containing 40 g. (0-33 mole) <strong>of</strong> dry<br />
1 Bechamp, Compt. rend., 1855, 40, 946 ; 1856, 42, 226.<br />
121
122 ACID CHLOKIDES<br />
benzoic acid, 100 c.c. <strong>of</strong> thionyl chloride are poured. The flask is<br />
now heated on the water bath to 80° in the fume chamber. When<br />
the vigorous evolution <strong>of</strong> gas (HC1 and SO2) has ceased (half an hour),<br />
the cooled mixture is poured into a distilling flask and the excess<br />
<strong>of</strong> thionyl chloride is as far as possible distilled through a downward<br />
condenser from a vigorously boiling water bath. (The distillate<br />
can be used again for the preparation <strong>of</strong> further amounts <strong>of</strong> benzoyl<br />
chloride.)<br />
The benzoyl chloride is now distilled from a wire gauze or over<br />
a faintly luminous flame. A long air condenser with a receiver<br />
similar to that used for acetyl chloride is employed. The first<br />
portion <strong>of</strong> the distillate, which consists chiefly <strong>of</strong> thionyl chloride,<br />
is fairly large (this material also may be used again). Then the<br />
bulk passes over at 194°-199°. Pure benzoyl chloride boils at 194°.<br />
Yield 40-42 g.<br />
Vacuum distillation, which yields a purer product, is also to be<br />
recommended here. Benzoyl chloride is a widely used laboratory<br />
product.<br />
The hydroxyl <strong>of</strong> a COOH-group may be replaced by chlorine by<br />
means <strong>of</strong> reactions, in part similar to that described above for the replacement<br />
<strong>of</strong> alcoholic hydroxyl groups by halogen.<br />
In practice acid chlorides are almost always prepared by the action<br />
<strong>of</strong> PC13, PC15, or SOC12 (in exceptional cases POC13) on the acids themselves<br />
or, also, in many cases, on their alkali salts. The choice <strong>of</strong> the<br />
chloride to be used depends (1) on the ease with which the acid concerned<br />
reacts, and (2) on the boiling point <strong>of</strong> the acid chloride. If,<br />
for example, as in the case <strong>of</strong> acetic acid and its homologues, PC13<br />
reacts readily with the formation <strong>of</strong> acid chlorides, then this chloride is<br />
used in preference to the more energetic PC15. In the reaction, the<br />
mechanism <strong>of</strong> which is discussed below, phosphorous acid is formed<br />
according to the equation :<br />
3CH3.Cf + PCl3 = 3CH3.C
ACID CHLOKIDES 123<br />
The course <strong>of</strong> the reaction may be regarded as proceeding in such a<br />
way that a mixed anhydride is first formed with elimination <strong>of</strong> HC1<br />
and that the anhydride then breaks down into acid chloride and SO2.<br />
R.C:O + SOC12 —^> R.C:O —> R.C:O<br />
OH O.SOC1 Cl 2-<br />
The course <strong>of</strong> the reaction is similar when the chlorides <strong>of</strong> phosphorus<br />
(or phosgene) are used.<br />
In cases where the reaction proceeds violently, chlor<strong>of</strong>orm or<br />
benzene is used as a diluent; this holds for the reaction with alcohols<br />
also. As a rule phosphorus oxychloride is only used with salts <strong>of</strong><br />
carboxylic acids. It reacts with these as follows :<br />
2 CH3.CO.ONa + POCl3 = 2 CH3.CO.Cl+JSfaP03 + NaCl .<br />
This reaction can be considered as having the advantage that the<br />
chlorine <strong>of</strong> the PC15 is more completely utilised than when the free<br />
acid is treated.<br />
Lower members <strong>of</strong> the series <strong>of</strong> acid chlorides are colourless liquids ;<br />
the higher members are colourless crystalline solids. At ordinary pressure<br />
most <strong>of</strong> them boil without decomposition. Vacuum distillation<br />
is only indicated with those <strong>of</strong> high molecular weight. The boiling<br />
points <strong>of</strong> the acid chlorides are lower than those <strong>of</strong> the acids, for the<br />
replacement <strong>of</strong> hydroxyl by chlorine usually causes a lowering <strong>of</strong> the<br />
boiling point :<br />
CH3.CO.C1 boiling point 51° C6H5.CO.C1 boiling point 198°<br />
CHg.CO.OH „ „ 118° CJL.CO.OH „ „ 250°<br />
The acid chlorides have a powerful pungent odour and fume when<br />
exposed to the air. Water decomposes them with the formation <strong>of</strong><br />
acids and hydrogen chloride. Often this decomposition takes place with<br />
exceptional ease since the chlorine atom is much more loosely attached<br />
to an acid radicle than to an alkyl. Whereas the conversion <strong>of</strong> an alkyl<br />
halide into an alcohol usually requires prolonged boiling with water,<br />
<strong>of</strong>ten with addition <strong>of</strong> sodium or potassium hydroxide, or <strong>of</strong> a carbonate<br />
or acetate, the analogous decomposition <strong>of</strong> an acid chloride is much more<br />
easy. Amongst the lower members the reaction takes place, even in<br />
the cold, with exceptional violence and almost immediately, whilst<br />
with the higher members, as, for example, benzoyl chloride, heating is<br />
required to induce the decomposition. Sulphonic acid chlorides (see<br />
benzenesulphonyl chloride, p. 192) even resist for a long time the action<br />
<strong>of</strong> boiling water. Alkalis naturally act much more energetically than<br />
water. Alcohols and phenols react with acid chlorides to form esters.<br />
Experiment (a).—Gradually pour 0-5 c.c. <strong>of</strong> acetyl chloride into a<br />
test tube containing 2 c.c. <strong>of</strong> water. If the water is very cold drops<br />
<strong>of</strong> the chloride may be seen to sink in the water without mixing.
124 ACID CHLOKIDES<br />
When the tube is shaken heat is developed and a vigorous reaction<br />
occurs.<br />
Experiment (6).—The same should be done with benzoyl chloride.<br />
Even on prolonged shaking no perceptible change takes place ; the<br />
mixture must be boiled for some time in order to cause complete<br />
decomposition. Treat benzoyl chloride in the same way with 2Nalkali.<br />
Experiment (c).—An equal volume <strong>of</strong> acetyl chloride is added<br />
drop by drop to 1 c.c. <strong>of</strong> alcohol in a test tube which is cooled in<br />
water. The mixture is then treated, while similarly cooled, with<br />
an equal volume <strong>of</strong> water and is carefully made slightly alkaline<br />
with sodium hydroxide. If a mobile layer <strong>of</strong> fragrant ethyl acetate<br />
fails to appear, finely powdered common salt is added until no<br />
more dissolves. This treatment causes the separation <strong>of</strong> the ethyl<br />
acetate.<br />
Benzoyl chloride is mixed in the same way with excess <strong>of</strong> alcohol,<br />
and the odour is used as an indication <strong>of</strong> the rate <strong>of</strong> reaction.<br />
Acid chlorides are also used in order to determine whether or no<br />
an unidentified substance contains alcoholic or phenolic hydroxyl<br />
groups. If a substance reacts with an acid chloride, such a hydroxyl<br />
group is present, since all groups in which oxygen is combined in other<br />
ways, e.g. in ether linkage, are indifferent to this treatment. The<br />
reaction can be considerably facilitated by the addition <strong>of</strong> alkali or <strong>of</strong><br />
alkali carbonate.<br />
Finally, the action <strong>of</strong> acid chlorides on alcohols and phenols is also<br />
used to separate them from solutions or to characterise them. For<br />
this purpose benzoyl chloride is usually employed. Methyl alcohol, for<br />
example, gives with y-nitrobenzoyl chloride the beautifully crystalline<br />
methyl ester and small amounts <strong>of</strong> the alcohol can thus be separated<br />
from aqueous solution.<br />
Acid chlorides react with salts <strong>of</strong> carboxylic acids to give acid<br />
anhydrides (see next preparation).<br />
It must further be mentioned that the acylation <strong>of</strong> alcohols, phenols,<br />
and amines with acid chlorides (and also anhydrides) is now frequently<br />
carried out in pyridine solution instead <strong>of</strong> according to the older<br />
Schotten-Baumann method (action <strong>of</strong> acid chloride in aqueous-alkaline<br />
suspension). The hydrogen chloride is fixed by the pyridine.<br />
Acid chlorides react also very easily with ammonia and with primary<br />
and secondary organic bases :<br />
CH3.CO.Cl + 2 NH3 = CH3.CO.NH2 + NH4C1<br />
CH3.CO.Cl + 2 C6Hs.NH2 = C6H5.NH.CO.CH3 + C6H5.NH3C1 .<br />
Aniline Acetanilide
BENZOYL PEKOXIDE 125<br />
Experiments.—(a) Acetyl chloride is added drop by drop to<br />
aniline. Accompanied by strong hissing, a vigorous reaction occurs<br />
which ceases as soon as an approximately equal volume <strong>of</strong> the<br />
chloride has been added. The liquid is cooled in water while five<br />
volumes <strong>of</strong> water axe added. A copious precipitate <strong>of</strong> acetanilide is<br />
thrown down ; the amount can be increased by rubbing the walls <strong>of</strong><br />
the vessel with a glass rod. The precipitate is filtered <strong>of</strong>f and<br />
crystallised from a little hot water. Melting point 115°.<br />
(6) In the same way aniline is treated with benzoyl chloride.<br />
This reaction is also used to characterise organic bases and to<br />
identify through a melting-point determination small amounts, particularly<br />
<strong>of</strong> the liquid bases, by converting them into their usually<br />
crystalline acyl derivatives. In order to cause the whole <strong>of</strong> the base<br />
to react—one mole is fixed by the hydrochloric acid liberated—alkali<br />
or carbonate is added when aqueous solutions or suspensions are used<br />
and dry potassium carbonate or pyridine when anhydrous solvents<br />
are employed. Since tertiary bases do not react with acid (acyl)<br />
chlorides, no further replaceable hydrogen atom being present, it is<br />
possible by the use <strong>of</strong> an acid chloride to determine also whether a base<br />
is, on the one hand, primary or secondary, or, on the other hand,<br />
tertiary.<br />
The important application <strong>of</strong> acid chlorides in the Friedel-Crafts<br />
reaction (p. 343) may also be mentioned here.<br />
Hydrogen peroxide can also be acylated by the Schotten-Baumann<br />
process. In this way acyl peroxides are obtained.<br />
Preparation <strong>of</strong> Benzoyl Peroxide. 1 —Hydrogen peroxide (50 c.c.<br />
<strong>of</strong> about 10 per cent aqueous solution) kept well cooled in ice<br />
and continually shaken (preferably in a glass-stoppered bottle) is<br />
treated alternately with 4 iV-sodium hydroxide solution and benzoyl<br />
chloride, added each a few drops at a time ; the solution is maintained<br />
faintly alkaline throughout. After about 30 c.c. <strong>of</strong> alkali<br />
and 15 g. <strong>of</strong> benzoyl chloride have been used up, the hydrogen peroxide<br />
has been decomposed and the benzoyl peroxide has separated<br />
in crystalline flocks, while the odour <strong>of</strong> the chloride has almost completely<br />
disappeared. The peroxide is filtered with suction, washed<br />
with water, and dried. Yield 10-12 g. Crystallised from a little<br />
alcohol, with which it should be boiled for a short time only, the<br />
substance forms beautiful colourless prisms. Melting point 106°-<br />
108° decomp. Heat a small quantity rapidly in a dry test tube<br />
over a naked flame. An especially pure product is obtained when a<br />
1 von Pechmann and Vanino, Ber., 1894, 27, 1510.
126 ACETIC ANHYDKIDE<br />
concentrated chlor<strong>of</strong>orm solution <strong>of</strong> the peroxide is run into twice as<br />
much methyl alcohol. Benzoyl peroxide, like all organic peroxides,<br />
must be handled with some care.<br />
The simplest method for preparing alkylene oxides involves the<br />
use <strong>of</strong> benzoyl peroxide (Prileschaiev). In absolute ether or, still<br />
better, in benzene solution, it is broken by sodium ethoxide into the<br />
sodium salt <strong>of</strong> perbenzoic acid and ethyl benzoate. 1<br />
C8H8.C.O.O.C.CeH8 —> C6H5.C.O.ONa + H5C2O.C.C6H5 .<br />
5 6 6 0<br />
The unstable per-acid, which like all per-acids is much weaker than<br />
the corresponding carboxylic acid, is taken up in chlor<strong>of</strong>orm after<br />
acidification <strong>of</strong> the solution <strong>of</strong> the sodium salt. The chlor<strong>of</strong>orm<br />
solution serves in the reaction with unsaturated substances which has<br />
already been formulated on p. 111. Ethylene itself does not give this<br />
reaction.<br />
2. ACETIC ANHYDRIDE 2<br />
For the preparation <strong>of</strong> acetic anhydride the same apparatus as<br />
for acetyl chloride is employed.<br />
Acetyl chloride (54 g. =0-75 mole) is allowed to run drop by drop<br />
from a tap funnel on to 80 g. <strong>of</strong> finely powdered anhydrous sodium<br />
acetate prepared in the manner described below. When about half<br />
<strong>of</strong> the chloride has been added the experiment is interrupted for a<br />
short time in order to stir the pasty mass <strong>of</strong> material with a bent<br />
glass rod, the lower end <strong>of</strong> which has been flattened. The rest <strong>of</strong><br />
the acetyl chloride is then run in at such a rate that none passes over<br />
unchanged. The anhydride is now distilled from the residual salt<br />
by mean <strong>of</strong> a luminous flame kept constantly in motion. Complete<br />
conversion <strong>of</strong> the last traces <strong>of</strong> unchanged acetyl chloride to acetic<br />
anhydride is attained by adding 3 g. <strong>of</strong> finely powdered anhydrous<br />
sodium acetate to the distillate, which is finally fractionally distilled.<br />
Boiling point <strong>of</strong> acetic anhydride 138°. Yield 55-60 g. Use for<br />
acetylation, in Perkin's synthesis (Chap. V. 8, p. 232), preparation <strong>of</strong><br />
acetophenone (Chap. IX. 3 b, p. 346).<br />
The product should be tested for chlorine by boiling a sample with<br />
water and adding dilute nitric acid and a few drops <strong>of</strong> silver nitrate.<br />
In a similar way fine crystals <strong>of</strong> benzoic anhydride (m.p. 42°) can<br />
be prepared. This is also obtained when benzoic acid is boiled with<br />
1 Baeyer and Villiger, Ber., 1900, 33, 1575.<br />
2 C. Gerhardt, Ann. Chim., 1853, [iii.], 37, 313.
ACID ANHYDKIDES 127<br />
an excess <strong>of</strong> acetic anhydride (transformation <strong>of</strong> one anhydride into<br />
another).<br />
Preparation <strong>of</strong> Anhydrous Sodium Acetate.—The hydrated salt<br />
(3 H2O) is heated over a naked flame in a shallow iron or nickel dish.<br />
After the water <strong>of</strong> crystallisation has evaporated the material<br />
solidifies. By careful heating the anhydrous salt is now also fused.<br />
After resolidification the still warm substance is powdered and<br />
immediately transferred to an air-tight container. Commercial<br />
anhydrous acetate should also be fused before use.<br />
Acetyl chloride acts on sodium acetate in the manner expressed in<br />
the following equation :<br />
CH3.C=O<br />
CHg.CO.Cl + CH3.CO.ONa = \o + NaCl.<br />
CH3.C=O<br />
Mixed anhydrides which contain two different acid radicles can be<br />
prepared in this way from the chloride and salt <strong>of</strong> two different acids.<br />
Since, as has been shown above in the case <strong>of</strong> acetyl chloride, an<br />
acid chloride can be obtained from the alkali salt <strong>of</strong> an acid and POC13,<br />
it is not necessary when preparing an anhydride first to isolate the<br />
chloride. It may be preferable to make the latter act at once on an<br />
excess <strong>of</strong> the salt so that from POC13 and the salt an anhydride can<br />
be obtained directly in one operation (technical method). Write out<br />
the equation for this reaction.<br />
The lower members <strong>of</strong> the series <strong>of</strong> acid anhydrides are colourless<br />
liquids, the higher ones crystalline solids. They have a pungent odour<br />
and are insoluble in water, but dissolve in indifferent organic solvents.<br />
Their specific gravities are greater than that <strong>of</strong> water and their boiling<br />
points higher than those <strong>of</strong> the corresponding acids :<br />
Acetic acid 118°, acetic anhydride 138°.<br />
As a rule, their melting points are lower than those <strong>of</strong> the corresponding<br />
acids. The lower members can be distilled at ordinary pressure<br />
without decomposition ; distillation <strong>of</strong> the higher members must be<br />
carried out in vacuo.<br />
Towards water, alcohols, phenols, and bases the anhydrides behave,<br />
chemically, exactly as do the chlorides, except that the former react<br />
more slowly than the latter.<br />
Experiment.—To 3 c.c. <strong>of</strong> water 0-5 c.c. <strong>of</strong> acetic anhydride is<br />
added. It sinks to the bottom and does not dissolve even on prolonged<br />
shaking. If, however, the mixture <strong>of</strong> water and anhydride<br />
is warmed for a short time, the anhydride is hydrated ; it goes into
128 ACETIC ANHYDKIDE<br />
solution more rapidly if dilute alkali hydroxide solution is used<br />
instead <strong>of</strong> water.<br />
Acetic anhydride is very <strong>of</strong>ten used to introduce the acetyl group<br />
into an alcoholic or phenolic hydroxyl group or into a derivative <strong>of</strong><br />
ammonia HNRRj^. The reaction is accelerated to an extraordinary<br />
extent by the presence <strong>of</strong> a drop <strong>of</strong> concentrated sulphuric acid.<br />
Experiment.—Acetic anhydride is added to alcohol, aqueous<br />
ammonia, aniline, and phenol. A drop <strong>of</strong> concentrated sulphuric<br />
acid is added to the phenol mixture.<br />
By thermal decomposition on the surface <strong>of</strong> a glowing platinum<br />
wire, acetic anhydride loses water and is converted into ketene, the<br />
unimolecular anhydride <strong>of</strong> acetic acid (Wilsmore) :<br />
H3C.CO<br />
0 -H2O —>• 2H2C:CO.<br />
H3C.CO<br />
In practice ketene is prepared by the thermal decomposition <strong>of</strong><br />
acetone (Schmidlin) :<br />
CH3.CO.CH3 —> CH2:CO + CH4.<br />
Ketene can be prepared conveniently and in good yield by means <strong>of</strong><br />
E. Ott's " ketene lamp "}<br />
When water is excluded ketene also serves as an acetylating agent.<br />
When the close relationship between the two classes <strong>of</strong> compounds<br />
is examined more closely, the analogy <strong>of</strong> the anhydrides to the acid<br />
chlorides becomes more intelligible. In both, the hydroxyl <strong>of</strong> the carboxyl<br />
group is replaced by the anionic portion <strong>of</strong> an acid : in the chloride<br />
by Cl, in the anhydride by acetoxyl O.CO.CH3.<br />
The anhydrides <strong>of</strong> the organic acids can also be regarded as diacyloxides<br />
(acyl=acid radicle, e.g. CH3.CO = acetyl) and can be thus<br />
assimilated to the ethers, or dialkyl oxides. The ethers are amongst<br />
the most indifferent <strong>of</strong> all the conpounds <strong>of</strong> organic chemistry. Whence,<br />
then, comes the great reactivity <strong>of</strong> the similarly constituted anhydrides ?<br />
The weak point in the anhydride molecule is to be found, not at the<br />
oxygen bridge, but at the double linkage >C=O. Additions, e.g.<br />
<strong>of</strong> water and ammonia, take place here :<br />
H3C.C=O<br />
><br />
H,C.C=O<br />
•"•3<br />
H 3 C . C = O<br />
><br />
O H<br />
; w i t h N H 3<br />
/ N H 2 |<br />
H g C . C ^ O H<br />
| H 3 C . C = O<br />
J . p r . C h e m . , 1 9 3 1 , 1 3 0 , 1 7 7 ; cf. a l s o B e r l a n d K u l l m a n n , B e r . , 1 9 3 2 , 6 5 , 1 1 1 4 .
ACBTAMIDB 129<br />
The - intermediate products, which are represented within brackets,<br />
are exceptionally labile since they contain OH and the negative acetoxyl<br />
group attached to the same carbon atom (cf. p. 103); they therefore<br />
decompose into two molecules <strong>of</strong> acid or, in the case <strong>of</strong> ammonia, into<br />
acetic acid and acetamide. The reaction with alcohols is to be formulated<br />
in the same way. It will be observed that, when an acyl<br />
group is introduced (into an alcohol, amine, etc.) by means <strong>of</strong> an anhydride,<br />
one <strong>of</strong> the two acid radicles in the molecule is always converted<br />
into the acid and is consequently not used in the acylation. The<br />
great reactivity <strong>of</strong> the acid chlorides has the same cause as that discussed<br />
in connexion with the anhydrides.<br />
3. ACETAMIDE 1<br />
Ammonium acetate (80 g.)—from ammonium carbonate and<br />
glacial acetic acid 2 —and glacial acetic acid (60 c.c.) in a small roundbottomed<br />
flask fitted with a Widmer column are kept gently boiling<br />
on a wire gauze for five to six hours. Care is taken that the thermometer<br />
fixed in the upper part <strong>of</strong> the column scarcely registers<br />
over 103° ; the acetic acid and the water formed in the reaction<br />
distil over slowly at the top <strong>of</strong> the column and can be condensed by<br />
means <strong>of</strong> a small condenser jacket slipped over the side tube. When<br />
about 80 c.c. <strong>of</strong> liquid have collected in the measuring cylinder used<br />
as a receiver stronger heat is applied until the thermometer registers<br />
140°. The contents <strong>of</strong> the flask, after being allowed to cool somewhat,<br />
are transferred while still warm to an ordinary distilling flask<br />
and, after a small preliminary fraction has passed over, the bulk is<br />
collected at 195°-220°. If the product does not solidify completely<br />
when cooled and stirred, the liquid portion is removed as completely<br />
as possible by nitration on a Biichner funnel and the residue<br />
is dried on a porous plate in an ordinary desiccator. A further<br />
quantity <strong>of</strong> acetamide can be obtained from the filtrate by distillation.<br />
The pure compound boils at 223°. A small sample<br />
may be recrystallised from benzene. Melting point 80°. Yield<br />
55-60 g. Use for preparation <strong>of</strong> acetonitrile (Chap. II. 5, p. 137);<br />
<strong>of</strong> methylamine (Chap. II. 8, p. 152).<br />
1 In principle according to Francois, Chem. Zentr., 1906, I, 1089. Hitch and<br />
Gilbert, J. Amer. Chem. Soc., 1913, 35, 1780; W. A. Noyes and Goebel, ibid., 1922,<br />
44, 2294.<br />
2 Finely powdered ammonium carbonate ia added to 60 c.c. <strong>of</strong> glacial acetic<br />
acid at 40°^50° until a sample <strong>of</strong> the solution, after dilution with water, reacts<br />
alkaline. It must be remembered that in this process 0-5 mole <strong>of</strong> water is formed<br />
per mole <strong>of</strong> ammonium acetate.<br />
K
130 ACBTAMIDE<br />
Amides are prepared, quite generally, from the acids by subjecting<br />
the ammonium salts to dry distillation, or still better, by heating them<br />
for a long time at a high temperature.<br />
Formerly acetamide was usually prepared by heating ammonium<br />
acetate to 200° in a sealed tube. By this method, however, the reaction<br />
cannot proceed to completion because the water set free in the reaction<br />
partly hydrolyses the amide again :<br />
CH3.C—0NH4 —> CH3.C—NH2 + H2O .<br />
II \\<br />
0 0<br />
When, as in the process given, the water formed is removed from<br />
the reaction mixture by distillation, the back reaction is restricted and<br />
the yield increased. At the same time the excess <strong>of</strong> acetic acid counteracts<br />
the dissociation <strong>of</strong> the salt which takes place according to the equa-<br />
tlOn : CH3.C—0NH4 —> CH3.COOH + NH3 .<br />
0<br />
See, in this connexion, the discussion <strong>of</strong> the law <strong>of</strong> mass action<br />
on p. 142 el seq.<br />
A good method for the preparation <strong>of</strong> acetamide is to pass ammonia<br />
gas into an ethereal solution <strong>of</strong> acetic anhydride, evaporate the ether<br />
and extract the residual mixture <strong>of</strong> ammonium acetate and acetamide<br />
with benzene in an extraction apparatus (Fig. 25). The salt remains undissolved.<br />
Amides can also be prepared by the action <strong>of</strong> ammonia on<br />
acid chlorides and esters.<br />
In addition, they are formed in the partial hydration <strong>of</strong> nitriles<br />
by the action <strong>of</strong> strong mineral acids. An example <strong>of</strong> this reaction is<br />
given on p. 140.<br />
Experiment.—Finely powdered ammonium carbonate (10 g.) is<br />
thoroughly mixed in a porcelain basin with 5 g. <strong>of</strong> benzoyl chloride,<br />
by stirring with a pestle ; the mixture is then warmed on the water<br />
bath till the odour <strong>of</strong> the chloride has disappeared. Water is now<br />
added and the mixture is filtered with suction, washed on the funnel<br />
with water, and crystallised from the same liquid. Melting point <strong>of</strong><br />
benzamide 128°.<br />
Apart from the first member <strong>of</strong> the series, formamide, HC0.NH2,<br />
which is a liquid, the amides are colourless crystalline solids. The<br />
lower members are readily soluble in water and the higher ones can<br />
generally be recrystallised from hot water. The boiling points are<br />
much higher than those <strong>of</strong> the corresponding acids :<br />
Acetic acid, boiling point 118°. Propionic acid, boiling point 141°.<br />
Acetamide, „ „ 223°. Propionamide, „ „ 213°.
ACETAMIDE 131<br />
Owing to the acyi group to which, it is bound, the amino-group<br />
loses its basic character almost entirely. Salts <strong>of</strong> the amides with<br />
strong acids are indeed known, but such salts are immediately and completely<br />
decomposed into their constituents by water. Only urea, the<br />
diamide <strong>of</strong> carbonic acid, forms stable salts, the existence <strong>of</strong> which is<br />
made possible by the second NH2-group.<br />
The compounds <strong>of</strong> the amides with bivalent mercury are characteristic.<br />
In them the metal is united to the nitrogen and is not in ionic combination,<br />
as in a salt. They are formed by the action <strong>of</strong> mercuric oxide, e.g.<br />
2CH3.CO.NH2 + HgO —y (CH3.CO.NH)2Hg + H2O .<br />
Experiment.—A small quantity <strong>of</strong> acetamide is dissolved in water,<br />
mixed with a little yellow oxide <strong>of</strong> mercury, and warmed. The oxide<br />
goes into solution and the compound formulated above is formed.<br />
The dehydration which leads to the formation <strong>of</strong> nitriles and the<br />
action <strong>of</strong> hypohalides on amides are dealt with in the following preparations.<br />
The amino-group <strong>of</strong> the amides, as distinguished from that<br />
<strong>of</strong> the amines, is more or less easily removed by hydrolytic agents,<br />
acids being re-formed. For the cause <strong>of</strong> this difference in behaviour<br />
compare the explanation given on p. 128.<br />
Experiment.—A little acetamide is heated in a test tube with<br />
2 iV-sodium hydroxide solution. An intense odour <strong>of</strong> ammonia<br />
develops and sodium acetate is formed in the solution. The presence<br />
<strong>of</strong> acetic acid is proved by making the solution just acid to<br />
Congo red paper with concentrated hydrochloric acid, shaking the<br />
tube while closing its mouth with the thumb and then heating the<br />
solution to the boiling point (porous pot to prevent bumping).<br />
Litmus paper held over the mouth <strong>of</strong> the tube turns red. (General<br />
test for volatile acids.)<br />
The reaction between amides and PC15, which leads by way <strong>of</strong> the<br />
amide chlorides to the imide chlorides, need merely be mentioned here.<br />
4. UREA AND SEMICARBAZIDE<br />
(a) POTASSIUM CYANATE 1 BY OXIDATIVE FUSION 2<br />
Potassium ferrocyanide (200 g.) is completely dehydrated by careful<br />
heating in a porcelain basin or on an iron plate ; the crystals<br />
1 Since there is only one cyanic acid, we do not consider it correct to drop this<br />
name and, as is <strong>of</strong>ten done, to call the substance tso-cyanic acid.<br />
2 C. A. Bell, Chem. News, 1875, 32, 99; Gattermann, Ber., 1890, 23, 1223;<br />
H. Erdmann, Ber., 1893, 26, 2442.
132 POTASSIUM CYANATB AND UREA<br />
must be completely disintegrated and a sample may not produce a<br />
film <strong>of</strong> moisture on the walls <strong>of</strong> a tube in which it is heated. In the<br />
same way 150 g. <strong>of</strong> potassium dichromate are freed from adherent<br />
moisture. After being powdered separately, the two salts are<br />
thoroughly mixed in a mortar and the mixture, in portions <strong>of</strong> 4 to<br />
5 g., is dropped into an iron basin or on to a large iron plate which is<br />
strongly heated (but not, however, to red heat) by a powerful burner<br />
(Teclu or triple burner). The temperature should be high enough<br />
to cause vigorous glowing <strong>of</strong> each portion, but the spongy black<br />
mass thus formed must on no account be allowed to melt. After<br />
the very rapid completion <strong>of</strong> its oxidation, each portion is scraped<br />
aside by means <strong>of</strong> a broad metallic spatula or is entirely removed<br />
from the plate. The whole amount can be treated in this way in<br />
one to one and a half hours. The various portions <strong>of</strong> the material,<br />
collected in a round-bottomed flask, are covered with hot 80 per<br />
cent alcohol (800 c.c), which is then kept boiling for three minutes<br />
by heating the flask on a vigorously boiling water bath. The clear<br />
solution which is formed is decanted from the black deposit into<br />
a conical flask, which is immediately placed on ice and shaken well<br />
so that its contents are cooled as quickly as possible. After the<br />
flask has been allowed to stand for a short time, the mother liquor<br />
from the deposited cyanate crystals is poured <strong>of</strong>f into the roundbottomed<br />
flask containing the melt and the extraction <strong>of</strong> the latter<br />
is repeated until all the salt has been extracted. (Five to six<br />
times. A sample in a test tube should no longer deposit crystals on<br />
cooling.) The salt is now filtered as dry as possible at the pump,<br />
washed twice with rectified spirit, and then three times with ether,<br />
and finally thoroughly dried in a desiccator. Average yield 80 g.<br />
Potassium cyanate is also conveniently prepared by oxidation <strong>of</strong><br />
cyanide with permanganate in aqueous solution. 1<br />
(6) UREA<br />
Potassium cyanate (40 g.) and ammonium sulphate (40 g.) are<br />
dissolved in 500 c.c. <strong>of</strong> water in a porcelain basin, and the solution<br />
is evaporated to dryness on the water bath. The residue is exhaustively<br />
extracted in a round-bottomed flask with boiling absolute<br />
alcohol, and the alcoholic solution is concentrated until, on<br />
1 J. Volhard, Annalen, 1890, 259, 378 ; F. Ullmann and Uzbachian, Ber., 1903,<br />
36, 1806 ; Marckwald, Ber., 1923, 56, 1325. The best method is that <strong>of</strong> Gall and<br />
Lehmann, Ber., 1928, 61, 675.
POTASSIUM CYANATB AND UEBA 133<br />
cooling and inoculating, crystallisation sets in. Melting point 132°.<br />
The remainder <strong>of</strong> the urea in the mother liquor is isolated as nitrate<br />
after evaporation <strong>of</strong> the alcohol.<br />
To prepare the nitrate a few grammes <strong>of</strong> urea are dissolved in a<br />
few c.c. <strong>of</strong> water and concentrated nitric acid is added drop by drop.<br />
The salt separates in fine crystals. Urea nitrate is rather soluble<br />
in water, and this fact must be kept in mind when washing it.<br />
Wohler's synthesis <strong>of</strong> urea by which a product <strong>of</strong> the living cell was<br />
first prepared artificially more than a century ago is the prototype <strong>of</strong><br />
many addition reactions which take place with the reactive molecules <strong>of</strong><br />
cyanic acid and its esters, as well as with the series <strong>of</strong> analogous thiocompounds.<br />
In these reactions NH3 is added to the C = N double bond :<br />
O.-C.-NH *"% O:C<br />
2<br />
It is immaterial for this explanation whether it is assumed that the<br />
salt itself is converted or that dissociation first occurs.<br />
Reaction with amines gives substituted ureas (cf. methylurea p. 271)<br />
—with hydrazine for example, semicarbazide :<br />
O:C:NH + H2N.NH2 —>• 0:C
134 SBMICAEBAZIDB<br />
The esters <strong>of</strong> carbamic acid, the urethanes, which are formed by<br />
combination <strong>of</strong> alcohols with compounds <strong>of</strong> the cyanic acid series,<br />
are stable substances. The reaction by which they are formed is,<br />
likewise, capable <strong>of</strong> undergoing many variations. It may be recalled<br />
that a second method <strong>of</strong> synthesising them consists in acting on the<br />
esters <strong>of</strong> chlor<strong>of</strong>ormic acid with ammonia and amines.<br />
(c) SEMICAEBAZIDE 1<br />
Hydrazine sulphate (52 g.) and 21 g. <strong>of</strong> anhydrous sodium carbonate<br />
are dissolved in 200 c.c. <strong>of</strong> boiling water. The solution is<br />
cooled to 50°, a solution <strong>of</strong> 35 g. <strong>of</strong> potassium cyanate in 100 c.c. <strong>of</strong><br />
water is added, and the whole is allowed to stand over night. After<br />
small amounts <strong>of</strong> hydrazodicarbonamide, produced in the reaction<br />
H2N.CO.NH.NH2 + O=C=NH -> H2N.CO.NH.NH.CO.NH2, have<br />
been removed by filtration, 60 c.c. <strong>of</strong> acetone are added to the<br />
solution, which is again allowed to stand, with frequent shaking,<br />
for twenty-four hours. The acetone semicarbazone which has then<br />
crystallised out is filtered dry at the pump, washed with a little<br />
water, and dried on a porous plate or in vacuo.<br />
The mother liquor is evaporated to dryness on the water bath,<br />
and the powdered residue is extracted with alcohol in an extraction<br />
apparatus. Semicarbazone crystallises out in the flask <strong>of</strong> the apparatus.<br />
If a sample <strong>of</strong> the main portion <strong>of</strong> the material leaves a considerable<br />
amount <strong>of</strong> ash when ignited on platinum foil, this portion<br />
also should be extracted in the same way.<br />
To decompose the semicarbazone it is gently warmed with concentrated<br />
hydrochloric acid (8 c.c. for each 10 g. <strong>of</strong> material) until<br />
dissolution is just complete. On cooling the solution semicarbazide<br />
hydrochloride sets to a thick crystalline mass which is filtered dry<br />
at the pump and washed, first with a little cold hydrochloric acid<br />
(1 : 1), then twice with 3 to 5 c.c. portions <strong>of</strong> ice-cold alcohol. The<br />
salt is dried in a desiccator. Yield 22-25 g.<br />
In order to obtain the free semicarbazide, 5-5 g. <strong>of</strong> the hydrochloride<br />
are ground in a small mortar with 4-5 g. <strong>of</strong> anhydrous sodium<br />
acetate (see p. 127). The paste produced by the formation <strong>of</strong> free<br />
acetic acid is transferred with a spatula to a 100 c.c. conical flask;<br />
the last portions are washed in with absolute alcohol and the contents<br />
<strong>of</strong> the flask are then boiled on the water bath with (altogether) 50 c.c.<br />
<strong>of</strong> absolute alcohol. During the boiling the flask is frequently<br />
1 Thiele and Stange, Ber., 1894, 27, 31; H. Biltz, Annalen, 1905, 339, 250.
UEBA AND UEIC ACID FKOM UEINB 135<br />
shaken. The hot mixture is freed from precipitated sodium chloride<br />
by immediate filtration through a Biichner funnel provided with a<br />
hardened filter paper. On cooling, the free semicarbazide slowly<br />
crystallises from the clear nitrate in large prisms which have the<br />
appearance <strong>of</strong> urea crystals. Sparingly soluble in alcohol, very<br />
soluble in water.<br />
Experiments.—Being a primary hydrazide (<strong>of</strong> carbamic acid),<br />
semicarbazide reduces ammoniacal silver solutions and Fehling's<br />
solution. It reacts readily with aldehydes and ketones with the<br />
elimination <strong>of</strong> water and formation <strong>of</strong> semicarbazones, which, since<br />
they are more easily hydrolysed than are phenylhydrazones and<br />
oximes, are to be preferred to the latter for purposes <strong>of</strong> separation<br />
and purification <strong>of</strong> carbonyl compounds. Shake an aqueous solution<br />
<strong>of</strong> the hydrochloride (prepared as described above) with a<br />
few drops <strong>of</strong> benzaldehyde, isolate the semicarbazone and purify<br />
it by recrystallisation from alcohol. Melting point 214° decomp.<br />
Benzaldehyde semicarbazone is decomposed into its constituents<br />
by gentle warming with concentrated hydrochloric acid.<br />
The ketones and aldehydes, the preparation <strong>of</strong> which is described<br />
later, should be characterised in the same way by their semicarbazones.<br />
(d) UREA (AND URIC ACID) FROM URINE 1<br />
Urine (2 1.) in a porcelain basin is evaporated to a syrup on the<br />
water bath. The flame is extinguished and the hot syrup is stirred<br />
with 500 c.c. <strong>of</strong> alcohol. After some time the clear extract is decanted<br />
and the residue is again warmed and once more digested in<br />
the same way with 500 c.c. <strong>of</strong> alcohol. If necessary, the combined<br />
extracts are filtered, most <strong>of</strong> the alcohol they contain is removed by<br />
distillation, and the aqueous-alcoholic residue, after transference to<br />
a small porcelain basin, is evaporated to dryness on the water<br />
bath. The dry residue is well cooled and is kept in an efficient<br />
freezing mixture while two volumes <strong>of</strong> colourless concentrated nitric<br />
acid are slowly added with thorough stirring. After the product has<br />
stood for twelve hours, the paste <strong>of</strong> urea nitrate is filtered dry at the<br />
pump, washed with a little ice-cold nitric acid (1 : 1), again filtered<br />
with suction till no more liquid drains <strong>of</strong>f, and suspended in 100-150<br />
c.c. <strong>of</strong> warm water. To this suspension barium carbonate is added<br />
1 Salkowski, Prakt. d. physiol. u. path. Chemie, p. 161, Berlin, 1900.
136 UEBA AND UEIC ACID FKOM UEINE<br />
gradually in small portions until the liquid is neutral (addition <strong>of</strong><br />
excess <strong>of</strong> the carbonate is to be avoided). When this stage is reached<br />
the liquid is boiled with a little animal charcoal (a few portions from<br />
the point <strong>of</strong> a knife) filtered with suction while hot, and, after the<br />
material on the funnel has been washed once with hot water, the<br />
filtrate is evaporated to dryness. Urea, which is readily soluble in<br />
hot alcohol, is completely extracted from the residue with this<br />
solvent and is crystallised after concentration <strong>of</strong> the alcoholic solution.<br />
Yield 20-25 g.<br />
The amount <strong>of</strong> urea excreted daily by an adult is 25 to 30 g.<br />
(in an average <strong>of</strong> 1-5 1. <strong>of</strong> urine).<br />
Further Experiments.—A solution <strong>of</strong> urea is made alkaline with<br />
sodium hydroxide solution and is then shaken with a few drops <strong>of</strong><br />
bromine. Nitrogen is evolved. Compare, in this connexion, the<br />
H<strong>of</strong>mann reaction (p. 155).<br />
Nitrite solution is added to an acidified urea solution. Use <strong>of</strong><br />
urea for the removal <strong>of</strong> nitrous acid, e.g. in the preparation <strong>of</strong> ethyl<br />
nitrate (p. 148).<br />
Urea is but slowly hydrolysed. A solution is boiled with<br />
barium hydroxide solution. How can hydrolysis be detected ?<br />
Uric Acid.—The residue from which the urea was first extracted<br />
with alcohol is freed from the solvent by heating on the water bath<br />
and 50 c.c. <strong>of</strong> concentrated hydrochloric acid are added to it. When<br />
the resulting mixture has been allowed to stand for a day or two,<br />
0-3-0-5 g. <strong>of</strong> uric acid will be found to have separated and can be<br />
purified by dissolving in 150 c.c. <strong>of</strong> hot iV-sodium carbonate solution,<br />
adding 0 -4 g. <strong>of</strong> animal charcoal, filtering, and adding to the boiling<br />
filtrate drop by drop from a funnel, with shaking, 150 c.c. <strong>of</strong> Nhydrochloric<br />
acid. The uric acid separates as a beautiful crystalline<br />
powder from the hot liquid.<br />
Murexide Reaction.—A few centigrams <strong>of</strong> uric acid are evaporated<br />
to dryness in a small porcelain basin on the water bath with some<br />
drops <strong>of</strong> slightly diluted nitric acid. When ammonia is added to<br />
the residue an intense purple colour is produced.<br />
Uric acid is a normal product <strong>of</strong> metabolism. The chemistry <strong>of</strong><br />
the purines, the uric acid syntheses <strong>of</strong> Baeyer and Fischer, Behrend<br />
and Roosen, and W. Traube, the chemistry <strong>of</strong> adenine, guanine, caffeine,<br />
and their relationships to uric acid, should be studied.
ACETONITKILE 137<br />
5. NITRILES<br />
(a) ACETONITRILE X<br />
Dry acetamide (12 g. =0-2 mole) is well mixed with phosphorus<br />
pentoxide (20 g.) in a small dry flask fitted with a short downward<br />
condenser and the mixture is cautiously heated with a moderatesized<br />
luminous flame. A reaction, accompanied by frothing and<br />
bubbling, takes place. After a few minutes the acetonitrile is distilled<br />
by stronger heating and is collected in a test tube. To the<br />
distillate half its volume <strong>of</strong> water is added and then solid potassium<br />
carbonate is dissolved in the lower aqueous layer <strong>of</strong> liquid until<br />
saturation point is reached. The layers are now separated in a<br />
funnel having a short delivery tube, and the acetonitrile is redistilled<br />
from a small distilling flask containing a little phosphorus pentoxide,<br />
which ensures complete dehydration. Boiling point 82°. Yield<br />
about 6 g.<br />
(6) BENZYL CYANIDE<br />
In a round-bottomed flask (capacity 0-5 1.) fitted with a double<br />
neck attachment (Anschiitz attachment), reflux condenser, and<br />
dropping funnel, 30 g. <strong>of</strong> sodium cyanide are dissolved in 35 c.c. <strong>of</strong><br />
hot water and 50 c.c. <strong>of</strong> alcohol are added. Pure benzyl chloride<br />
(63 g. =0-5 mole) is then run in from the funnel in the course <strong>of</strong> ten<br />
minutes. Then the contents <strong>of</strong> the flask are boiled for three hours<br />
longer, cooled, and filtered through a small Biichner funnel. The<br />
alcohol is distilled <strong>of</strong>f from the filtrate in the filter flask (a capillary<br />
is used during the distillation and the temperature <strong>of</strong> the bath is<br />
kept at 40°-50°); the benzyl cyanide, separated from the solution<br />
<strong>of</strong> sodium chloride by means <strong>of</strong> a small separating funnel, is distilled<br />
in vacuo from a Claisen flask after drying for a short time over a small<br />
stick <strong>of</strong> calcium chloride. Boiling point 105°-109°/12 mm. The<br />
boiling point <strong>of</strong> the completely pure substance at 760 mm. is 232°.<br />
Yield about 45 g. By redistillation <strong>of</strong> the first and last portions <strong>of</strong><br />
the distillate this yield can be increased.<br />
Use for the preparation <strong>of</strong> phenylacetic acid (p. 140) and <strong>of</strong><br />
phenylnitromethane (Chap. VI. 8, p. 256).<br />
When an amide is heated with a dehydrating agent (P2O5, ¥£>5,<br />
PC15) it loses water and is converted into a nitrile, e.g.<br />
1 Dumas, AnnaUn, 1847, 64, 332 ; Buckton and W. H<strong>of</strong>mann, Annalen, 1856,<br />
100, 131.
138 BENZYL CYANIDE<br />
CH3.CO.NH2 —> CH3.C;N + H2O .<br />
Since, as has been described above, amides can be obtained by<br />
removal <strong>of</strong> water from the ammonium salts <strong>of</strong> acids, nitriles can be<br />
prepared directly from ammonium salts in one operation by heating<br />
them with a powerful dehydrating agent, e.g. ammonium acetate with<br />
CH3.COONH4 = CH3.CN + 2H2O.<br />
Nitriles can also be obtained by the method <strong>of</strong> Kolbe : alkyl iodides<br />
(bromides or chlorides) are heated with alkali cyanide (example,<br />
benzyl cyanide), or salts <strong>of</strong> alkylsulphuric acids are subjected to dry<br />
distillation with potassium cyanide :<br />
KO3S.OC2Hg + CNK —>• K2SO4 + C2H5.CN.<br />
The preparation <strong>of</strong> aromatic nitriles from diazo-compounds will be<br />
discussed later (p. 291).<br />
The lower nitriles are colourless liquids, the higher are crystalline<br />
solids. The solubility in water decreases progressively with increasing<br />
molecular weight.<br />
Acetonitrile possesses in a high degree the power <strong>of</strong> ionising electrolytes,<br />
i.e. salts, acids and bases dissolved in it conduct the electric<br />
current and do so much better than do similar solutions in alcohol,<br />
ether, or chlor<strong>of</strong>orm (Walden). The reactivity <strong>of</strong> the nitriles is due to<br />
the triple linkage between carbon and nitrogen, a linkage which permits<br />
a series <strong>of</strong> addition reactions to take place. Thus, on heating with<br />
water to 180° (in a sealed tube) or at a lower temperature in the presence<br />
<strong>of</strong> acids or alkalis, a molecule <strong>of</strong> water is added and the corresponding<br />
amide is re-formed :<br />
R.C. : N + H2O —^ R.C.N —>- R.C.NH2.<br />
HOH 0<br />
The reaction is analogous to the conversion <strong>of</strong> acetylene into acetaldehyde<br />
:<br />
HCPH + H20 —^ HC:CH —> HC.CH,.<br />
HOH 0<br />
In both cases the intermediate product, the " enol form ", is unstable,<br />
but alkyl derivatives, the so-called iminoethers, are known.<br />
Energetic hydrolysis by heating with slightly diluted sulphuric acid<br />
or with strong alkalis naturally converts the amide into a carboxylic<br />
acid and ammonia, so that, with such reagents, a nitrile is in practice<br />
directly converted into an acid. The method <strong>of</strong> carrying out this<br />
reaction is given on p. 140.<br />
If nascent hydrogen (e.g. from zinc and sulphuric acid or from sodium<br />
and alcohol) is allowed to act on nitriles, four hydrogen atoms are<br />
added and primary amines are formed (reaction <strong>of</strong> Mendius):
KEACTIONS OF NITEILBS 139<br />
CH3.CN + 4H —> CH3.CH2.NH2.<br />
Ethylamine<br />
Other less important but general reactions may be indicated by the<br />
following equations :<br />
CH3.CN + H2S —> CH3.CS.NH2,<br />
Thioacetamide<br />
Jf.OH<br />
CH3.CN + NH2.OH —>• CH3.<br />
Oxime <strong>of</strong> acetamide<br />
3 = CH3.CC =NR suggest another<br />
constitution, namely, that <strong>of</strong> carbimide >C = NH with bivalent carbon.<br />
The addition reactions <strong>of</strong> the nitriles (see above), which reactions are<br />
also characteristic <strong>of</strong> hydrocyanic acid, can equally well be explained<br />
on the basis <strong>of</strong> this second structural formula. In the nitrile form it<br />
is at the triple bond between carbon and nitrogen that addition takes<br />
place. In the " methylene form " this occurs at the two free valencies<br />
<strong>of</strong> the bivalent carbon atom, e.g. :<br />
,NHOH<br />
>C=NH<br />
+ H2NOH<br />
\<br />
*N]<br />
HOHK<br />
>C=NH<br />
The hydrochloride <strong>of</strong> formiminoether is <strong>of</strong> practical importance. It<br />
is produced in fine colourless crystals by passing dry hydrogen chloride<br />
into a solution <strong>of</strong> equimolecular amounts <strong>of</strong> anhydrous hydrogen cyanide<br />
and ethyl alcohol in absolute ether. The salt is slowly decomposed by<br />
standing for a long time in the cold with alcohol, when ethyl orth<strong>of</strong>ormate<br />
and ammonium chloride are formed :<br />
/OC2H5<br />
/OC2H5<br />
HC< + 2 HOCH2.CH3 = HCf-OC2H5 + NH4C1.<br />
^NH.HCl \OC2H5
140 HYDKOLYSIS OF PHENYLACETONITKILE<br />
This synthesis <strong>of</strong> ethyl orth<strong>of</strong>ormate is more elegant and smooth<br />
than that from chlor<strong>of</strong>orm and sodium ethoxide. Ethyl orth<strong>of</strong>ormate<br />
is used for preparing acetals <strong>of</strong> ketones, e.g.<br />
CH3.CO.CH2.COOC2H5 + HC(OC2H5)3 = CH3.C.CH2.COOC2H5 + HC:O<br />
Ethyl acetoacetate / \ I<br />
H5C2O OC2H5 C2H56<br />
6. HYDROLYSIS OF A NITRILE TO THE ACID<br />
PHENYLACETIC ACID 1<br />
Benzyl cyanide (40 g. =0-33 mole) is heated in a round-bottomed<br />
flask (capacity 0-5 1.), with a mixture <strong>of</strong> 50 c.c. <strong>of</strong> concentrated sulphuric<br />
acid and 30 c.c. <strong>of</strong> water. The flask is provided with an upright<br />
air condenser, and is placed in a conical (Babo) air bath. The<br />
heating is continued until the appearance <strong>of</strong> small bubbles <strong>of</strong> vapour<br />
indicates that a reaction, which rapidly becomes violent, has set in ;<br />
the liquid boils up, and white fumes are emitted. It is allowed to<br />
cool and then two volumes <strong>of</strong> water are added. After some time<br />
the phenylacetic acid which has crystallised out is filtered <strong>of</strong>f with<br />
suction. If a sample <strong>of</strong> the material does not form a clear solution<br />
with sodium carbonate in water (presence <strong>of</strong> phenylacetamide), the<br />
whole <strong>of</strong> the crude material is shaken with sodium carbonate solution<br />
and the mixture is filtered. From the clear filtrate phenylacetic<br />
acid is reprecipitated with sulphuric acid, and can be recrystallised<br />
directly from a rather large volume <strong>of</strong> hot water or, after drying,<br />
from petrol ether. Because <strong>of</strong> its low melting point (76°) it <strong>of</strong>ten<br />
separates at first as an oil, but it can also be conveniently purified by<br />
distillation in vacuo from a sausage flask. 2<br />
The yield amounts to 34-38 g., and can be slightly increased by<br />
extracting the first mother liquor, from the sulphuric acid treatment,<br />
with ether.<br />
Benzyl cyanide is always lost by evaporation in the rather violent<br />
hydrolysis described above; this can be avoided by boiling the<br />
benzyl cyanide (40 g.) under a reflux condenser for forty-five minutes<br />
with a mixture <strong>of</strong> water, concentrated sulphuric acid, and glacial<br />
acetic acid (40 c.c. <strong>of</strong> each). After cooling, the product is poured<br />
into water.<br />
Under milder conditions (3 g. <strong>of</strong> benzyl cyanide dissolved in<br />
8 c.c. <strong>of</strong> concentrated sulphuric acid and after standing for six hours,<br />
1 Staedel, Ber., 1886, 19, 1951.<br />
2 Adams and Thai, <strong><strong>Org</strong>anic</strong> Syntheses, II, 1922, p. 64.
BSTBES 141<br />
pouring into 50 c.c. <strong>of</strong> water) the hydrolysis leads, for the most part,<br />
only to the amide. How is any phenylacetic acid, formed at the<br />
same time, to be separated ? Phenylacetamide melts at 155°.<br />
There are various methods <strong>of</strong> hydrolysing nitriles; the operation<br />
usually requires the use <strong>of</strong> powerful reagents, strong acids or strong<br />
alkalis. Sometimes indirect methods are adopted. The ready addition<br />
<strong>of</strong> hydrogen sulphide to the nitrile, forming a thioamide (p. 139), may,<br />
for example, be utilised, since the thioamides are readily hydrolysed.<br />
Esters <strong>of</strong> the required acid are also easily obtained by passing hydrogen<br />
chloride into the hot alcoholic solution <strong>of</strong> the nitrile. Imino-esters are<br />
formed, and their NH-group is hydrolytically replaced by 0 with extraordinary<br />
ease. Compare the example on p. 254.<br />
7. ESTERS<br />
(a) ETHYL ACETATE FROM ACETIC ACID AND ALCOHOL 1<br />
A half-litre flask is fitted with a two-holed cork through which<br />
are inserted a dropping funnel and a tube connected with a long<br />
downward condenser. Alcohol and concentrated sulphuric acid<br />
(50 c.c. <strong>of</strong> each) are poured into the flask and the mixture is heated<br />
in an oil bath until the temperature reaches 140°. As soon as this<br />
is the case a mixture <strong>of</strong> alcohol and glacial acetic acid (400 c.c. <strong>of</strong><br />
each) is gradually run in from the dropping funnel at the same rate<br />
as that at which the ethyl acetate formed distils. In order to free<br />
the distillate from acetic acid which has been carried over, it is<br />
shaken in an open flask with moderately concentrated sodium carbonate<br />
solution until the upper layer no longer reddens blue litmus<br />
paper. This layer is then separated in a tap funnel and, after filtration<br />
through a dry folded filter, is freed from alcohol by being shaken<br />
with a solution <strong>of</strong> 100 g. <strong>of</strong> calcium chloride in 100 g. <strong>of</strong> water. The<br />
two liquids are separated again in a funnel and the upper one is<br />
dried with granulated calcium chloride and finally distilled on the<br />
water bath. Boiling point 78°. Yield 80-85 per cent <strong>of</strong> the<br />
theoretical. Use in the preparation <strong>of</strong> ethyl acetoacetate and <strong>of</strong><br />
acetylacetone, see pp. 251, 252.<br />
Ethyl benzoate is prepared in a similar way, by boiling benzoic acid<br />
(30 g.) in 100 c.c. <strong>of</strong> absolute alcohol for four hours under reflux condenser<br />
with 3 c.c. <strong>of</strong> concentrated sulphuric acid. Most <strong>of</strong> the<br />
alcohol is then removed by distillation, 300 c.c. <strong>of</strong> water are added,<br />
1 Bull. Soc. dim., 1880, 33, 350.
142 MASS ACTION<br />
and the liquid is extracted with ether. By shaking with sodium<br />
carbonate solution, acid is removed from the ethereal solution, which<br />
is next dried over sodium sulphate over night. When the ether has<br />
been evaporated, the residual ethyl benzoate is distilled. Boiling<br />
point 212°. Yield 30 g.<br />
The formation <strong>of</strong> an ester from acid and alcohol corresponds in a<br />
formal way to salt formation from acid and metallic hydroxide.<br />
N03H + NaOH = NO3Na + H2O<br />
CH3.COOH + C3H5OH = CH3.COOC2H5 + H2O.<br />
As far as the velocity and the extent <strong>of</strong> the conversion are concerned,<br />
the two processes are, however, altogether different. Whereas<br />
an acid is practically instantaneously and completely converted into a<br />
salt by an equivalent amount <strong>of</strong> a sufficiently strong base (neutralisation),<br />
a process on which, indeed, alkalimetry and acidimetry depend,<br />
it is not possible to obtain from equimolecular amounts <strong>of</strong> acid and<br />
alcohol the theoretical (calculated) amount <strong>of</strong> ester. A certain maximal<br />
quantity <strong>of</strong> ester is formed, but always falls short <strong>of</strong> the theoretical,<br />
and it is impossible, even by indefinitely extending the duration <strong>of</strong> the<br />
reaction, to make the unchanged acid and alcohol produce ester in<br />
excess <strong>of</strong> that maximum. If, for example, equimolecular amounts <strong>of</strong><br />
acetic acid and alcohol are allowed to interact in a closed system,<br />
only two-thirds <strong>of</strong> each enter into reaction, and it is impossible to<br />
induce the remaining third <strong>of</strong> acetic acid to react with that <strong>of</strong> alcohol.<br />
The maximum yield <strong>of</strong> ester therefore amounts to only two-thirds, or<br />
66-7 per cent, <strong>of</strong> the theoretical quantity. The quantitative difference<br />
in the course <strong>of</strong> the two reactions mentioned above depends on the<br />
fact that esterification is a so-called " reversible reaction ", i.e. one in<br />
which the reaction products represented on the right-hand side <strong>of</strong> the<br />
equation (ester and water) also interact in the opposite direction :<br />
CH3.COOH + HO.C2H5 —> CH3.COOC2H5 + H2O .<br />
Strictly speaking, all chemical reactions are reversible, but when the<br />
extent <strong>of</strong> the reverse reaction is immeasurably small and, consequently,<br />
the transformation as a whole proceeds practically in one direction only,<br />
the reversibility is neglected. The synthesis <strong>of</strong> water from its elements<br />
is a reaction <strong>of</strong> this kind. But we should nevertheless bear in mind<br />
that already at + 2000° the opposite reaction (decomposition) takes<br />
place to such an extent that we must use the equation :<br />
2 H2 + O2 ^T~> 2 H2O .<br />
The conditions <strong>of</strong> the reaction are thus controlled by the temperature,<br />
and indeed in such a way that endothermic reactions (i.e. those which<br />
involve the absorption <strong>of</strong> energy) are, in general, favoured by a rise <strong>of</strong>
BSTBES 143<br />
the temperature, whilst on the other hand exothermic reactions are<br />
favoured by lowering it.<br />
After this brief characterisation <strong>of</strong> reversibility, we may use the<br />
example <strong>of</strong> esterification to consider next the question how the limitation<br />
<strong>of</strong> the reaction is to be explained. To the extent that acid and<br />
alcohol interact, and their reaction products, ester and water, are formed,<br />
the reverse reaction (ester + water = acid + alcohol) also gains in extent.<br />
A point is eventually reached at which just as many molecules <strong>of</strong> acid<br />
and alcohol react to form ester as molecules <strong>of</strong> ester and water are<br />
decomposed to form acid and alcohol. The two reactions balance<br />
each other, and it would seem as if the reacting system had come to a<br />
state <strong>of</strong> rest. But this apparent rest is simulated by the fact that, in<br />
unit time, equal numbers <strong>of</strong> ester molecules are formed and decomposed.<br />
A state <strong>of</strong> equilibrium has been attained, and, as the above considerations<br />
indicate, this state would also have been reached had the reaction proceeded<br />
at the outset from the opposite side between equimolecular<br />
amounts <strong>of</strong> ester and water. In the latter case the hydrolysis <strong>of</strong> the<br />
ester would likewise have been balanced sooner or later, according to<br />
the conditions prevailing, by the opposing esterification—in this case<br />
when 33-3 per cent <strong>of</strong> the ester had been decomposed. The equilibrium<br />
is therefore the same, no matter from which side it is approached;<br />
on this depends its exact experimental investigation, both here and in<br />
many other reactions.<br />
As has already been mentioned (p. 3), the velocity <strong>of</strong> a bimolecular<br />
reaction is proportional to the product <strong>of</strong> the reacting masses. Hence,<br />
if their concentrations are expressed in grammolecular weights the<br />
following simple relations hold :<br />
In these equations v is the velocity <strong>of</strong> esterification, v' is that <strong>of</strong><br />
hydrolysis. CAo, CJU, CB and Cw are the concentrations <strong>of</strong> the four<br />
substances involved, and k and h' are the velocity constants <strong>of</strong> the two<br />
reactions. The state <strong>of</strong> equilibrium is attained when on both sides<br />
<strong>of</strong> the chemical equation equal numbers <strong>of</strong> molecules interact, i.e. when<br />
the velocity is the same in both directions :<br />
v = v'<br />
Then also<br />
We • VAI • ft = ^E • ^W • ft ><br />
or<br />
P n y<br />
We • Wl ft -rr<br />
^B • ^W ft<br />
The last equation expresses the fact that at the point <strong>of</strong> equilibrium<br />
the products <strong>of</strong> each pair <strong>of</strong> the concentrations are inversely proporh'<br />
tional to the velocity constants. The quotient j-, usually designated<br />
by K, is the equilibrium constant.
144 KEACTION VELOCITY<br />
If this important constant is known it is readily possible, as will<br />
next be shown, to calculate in practice the extent <strong>of</strong> the transformation<br />
in an equilibrium reaction when the reactants are no longer present<br />
in equimolecular amounts, i.e. are not in equal molar concentrations.<br />
The calculation <strong>of</strong> K causes no difficulty in the present example,<br />
after what has been said about the position <strong>of</strong> the equilibrium. The<br />
resultant mixture contained one-third <strong>of</strong> a mole each <strong>of</strong> acid and alcohol<br />
and two-thirds <strong>of</strong> a mole each <strong>of</strong> ester and water. Therefore :<br />
TT 3 • 3 _JL<br />
It will now be possible to discover how and to what extent the for-<br />
mation <strong>of</strong> the ester can be affected if acetic acid and alcohol are not<br />
used in equimolecular proportions but, for example, in the ratio 1 : 2<br />
moles. If the amount (in moles) <strong>of</strong> ester present at equilibrium be<br />
x, then CE = x ; and since just as many molecules <strong>of</strong> water as <strong>of</strong> ester are<br />
formed, C w is also equal to x. The concentration <strong>of</strong> the acid is then<br />
1 - x, and that <strong>of</strong> the alcohol 2 - x, and, therefore :<br />
( l s ) ( 2 s )<br />
X . X<br />
From this equation it follows that x = 0-85, i.e. by increasing the<br />
concentration <strong>of</strong> the alcohol (or the acetic acid) the position <strong>of</strong> the equi-<br />
librium can be so shifted that the yield <strong>of</strong> ester is increased to 85 per<br />
cent. Advantage is very frequently taken <strong>of</strong> this practical possibility<br />
<strong>of</strong> altering the position <strong>of</strong> the equilibrium.<br />
In this connexion the following problems should be solved :<br />
How much ester will be formed when 3 moles <strong>of</strong> alcohol react<br />
with 1 mole <strong>of</strong> acetic acid ? How much when 30 g. <strong>of</strong> acetic acid and<br />
50 g. <strong>of</strong> alcohol are used ? In what proportions by weight must acetic<br />
acid and alcohol be caused to interact in order to convert 75 per cent <strong>of</strong><br />
the former into ester ?<br />
In all reactions which proceed entirely in one direction the amount<br />
<strong>of</strong> end product which could theoretically be expected can be calculated<br />
from the stoicheiometrical ratios. But in reactions in which an equili-<br />
brium is set up, it follows from the above considerations that we must<br />
know the equilibrium constant, which must be deduced by analysis.<br />
In the example chosen this evidently causes no difficulties; it is only<br />
necessary to determine by titration the concentration <strong>of</strong> the acetic<br />
acid in the equilibrium mixture.<br />
The R61e <strong>of</strong> the Sulphuric Acid.—If acetic acid and alcohol alone<br />
are heated together no noticeable reaction takes place even after a<br />
long time. The reaction is only started by added sulphuric acid,<br />
which may be replaced by gaseous hydrogen chloride. In all prob-<br />
ability these mineral acids form an unstable addition compound (more<br />
likely with the acetic acid) and this compound reacts with alcohol to
INFLUENCE OF THE CATALYST 145<br />
form the ester more rapidly than does the organic acid itself. The<br />
hydrolysis is also accelerated to the same extent as is the esterification,<br />
so that exactly the same equilibrium is attained as in the absence <strong>of</strong><br />
sulphuric acid, for instance, by heating the components to a high temperature<br />
in a sealed tube. The influence <strong>of</strong> the catalyst (the sulphuric<br />
acid) consists, therefore, only in an increase in the velocity <strong>of</strong> the reaction ;<br />
the position <strong>of</strong> the equilibrium is left unchanged. This important law<br />
holds for all reactions which are catalytically accelerated.<br />
It has been shown that the catalytic action <strong>of</strong> acids is proportional<br />
to their strength, <strong>of</strong> which their degree <strong>of</strong> ionisation is an expression.<br />
Conversely, the strength <strong>of</strong> an acid can be determined by measuring<br />
the rate <strong>of</strong> hydrolysis <strong>of</strong> an ester (usually methyl acetate) in aqueous<br />
solution in the presence <strong>of</strong> the acid concerned.<br />
An understanding <strong>of</strong> the theoretical principles which have been but<br />
briefly discussed in this section is indispensable to anyone who does not<br />
wish to practise organic chemistry merely as a culinary art.<br />
Other <strong>Methods</strong> for the preparation <strong>of</strong> Esters.—Esters are extremely<br />
easily formed from silver salts by the action <strong>of</strong> alkyl iodides :<br />
R.COOAg + I.R' —>• R.COOR' + Agl.<br />
The same object is attained by treating alkali salts with a dialkyl<br />
sulphate. Usually in this case only one alkyl group takes part in the<br />
reaction in accordance with the equation :<br />
R.COONa + (CH3)2SO4<br />
> R.COOCH3 + CH3.SO4Na .<br />
The alkyl group <strong>of</strong> the salt <strong>of</strong> the alkylsulphuric acid can also be<br />
made available for esterification if the temperature is raised sufficiently.<br />
The formation <strong>of</strong> esters from acid chlorides or anhydrides need<br />
only be recalled here. This method also has practical importance.<br />
For the esterification <strong>of</strong> difficultly accessible acids the elegant diazomethane<br />
method (p. 273) is most appropriate ; it usually proceeds very<br />
smoothly.<br />
The lower members <strong>of</strong> the series <strong>of</strong> esters are colourless liquids<br />
having pleasant fruity odours. The higher members, as well as most<br />
esters <strong>of</strong> aromatic acids, are crystalline substances. The boiling points<br />
<strong>of</strong> esters containing alkyl groups <strong>of</strong> low molecular weight (CH3, C2H5,<br />
C3H7) are lower than those <strong>of</strong> the corresponding acids :<br />
CH3.COOCH3 Boiling point 57°<br />
CH3.COOC2H5 „ „ 78°,<br />
CH3.COOH „ „ 118°.<br />
It is worthy <strong>of</strong> note that the melting points <strong>of</strong> the methyl esters are<br />
generally higher than those <strong>of</strong> the corresponding ethyl esters; thus,<br />
to take a well-known example, dimethyl oxalate (melting point 54°)<br />
is a solid whilst the diethyl ester is a liquid.<br />
The esters are <strong>of</strong>ten prepared as an end in themselves, and are used
146 ISOAMYL NITEITB<br />
technically, as solvents, perfumes, essences for fruit drinks, etc. But<br />
their most important role is connected with the transformation <strong>of</strong> the<br />
carboxyl group. Thus the alkyloxy group can be replaced by —NRR'<br />
as a result <strong>of</strong> the action <strong>of</strong> ammonia and <strong>of</strong> numerous ammonia derivatives<br />
containing at least one hydrogen atom directly attached to the<br />
nitrogen (primary and secondary amines, hydroxylamine, hydrazine).<br />
In this way amides and hydrazides <strong>of</strong> carboxylic acids are prepared.<br />
Special attention is called to the hydrazides : they are a stage in the<br />
Curtius degradation (pp. 153, 154). Attention may also be directed<br />
here to the large subject <strong>of</strong> ester condensations.<br />
Vigorous reduction with metallic sodium (and a little alcohol)<br />
converts esters into the corresponding primary alcohols (Bouveault) :<br />
R.COOR' —>• R.CH2OH + R'.OH.<br />
Finally, esters are very <strong>of</strong>ten prepared in order to purify acids, since<br />
the majority <strong>of</strong> esters—<strong>of</strong>ten in contrast to acids—can conveniently be<br />
distilled, especially in vacuo. From the pure esters the pure acids are<br />
then obtained by hydrolysis.<br />
The hydrolysis <strong>of</strong> the esters is carried out by prolonged heating with<br />
aqueous mineral acids or solutions <strong>of</strong> alkali hydroxides. See saponification<br />
<strong>of</strong> fats on p. 149. Alcoholic potassium hydroxide solution is an<br />
especially rapid hydrolytic agent.<br />
(6) ISOAMYL NITRITE l<br />
A mixture <strong>of</strong> amyl alcohol<br />
(44 g. =0-5 mole) and technical<br />
sodium nitrite solution (37 g. in<br />
70 c.c. <strong>of</strong> water) in a filtration jar<br />
is cooled to 0° in an ice-salt mixture.<br />
During the cooling the mixture<br />
is mechanically stirred, and<br />
this stirring is continued while<br />
concentrated hydrochloric acid (44<br />
c.c, d. 1-18) is slowly dropped in<br />
from a tap funnel (Fig. 51); the<br />
temperature is not allowed to rise<br />
above +5°. The reaction mixture<br />
is now shaken in a separating<br />
FIG. 51 funnel with about 200 c.c. <strong>of</strong> water,<br />
the aqueous layer is run <strong>of</strong>f, and<br />
the remaining liquid is washed first with dilute sodium carbonate<br />
Witt. Ber.. 1886. 19 915.
ETHYL NITEITB 147<br />
solution and then several times with water. After separation <strong>of</strong><br />
the two layers, the reaction product is clarified and dried over a<br />
little calcium chloride in a small conical flask. The dried liquid is<br />
then distilled at 50-60 mm. pressure (cf. p. 24) into a well-cooled<br />
receiver. The bulk <strong>of</strong> the liquid passes over at about 30° as a<br />
yellow oil. Yield 75 per cent <strong>of</strong> the theoretical.<br />
The esters <strong>of</strong> nitrous acid are characterised by their high velocities<br />
<strong>of</strong> formation and hydrolysis. They are almost instantaneously decomposed<br />
by mineral acids and in the method <strong>of</strong> preparation given this<br />
has been taken into account. The slightest excess <strong>of</strong> hydrochloric<br />
acid must be avoided. Advantage is taken <strong>of</strong> this property <strong>of</strong> the<br />
alkyl nitrites in all cases where it is desired to liberate nitrous acid in<br />
organic solvents (in which metallic nitrites are insoluble). Examples :<br />
addition <strong>of</strong> N2O3 to olefines, preparation <strong>of</strong> solid diazonium salts<br />
(p. 286), production <strong>of</strong> isonitroso-derivatives from ketones by the action<br />
<strong>of</strong> HN02. This synthesis is <strong>of</strong>ten also carried out in the manner <strong>of</strong><br />
the acetoacetic ester synthesis, with ketone, alkyl nitrite, and sodium<br />
ethylate ; the sodium salt <strong>of</strong> the isonitrosoketone is formed (cf. in this<br />
connexion p. 259) :<br />
R—CH2 R0.N:0 R—C:NONa<br />
| + —>• | + 2R0H.<br />
R_CO RONa R—C:O<br />
The elegant synthesis <strong>of</strong> sodium azide from hydrazine and alkyl<br />
nitrite is carried out in the same way (Stolle) :<br />
N \<br />
H2N—NH2 + RO—N=O + RONa —> II >N.Na + 2 ROH + H2O .<br />
W<br />
Ethyl nitrite is <strong>of</strong>ten used in preference to isoamyl nitrite because<br />
the removal <strong>of</strong> the amyl alcohol produced from the latter may be<br />
troublesome on account <strong>of</strong> its high boiling point (136°).<br />
Ethyl Nitrite.—To the mixture <strong>of</strong> the above sodium nitrite solution<br />
with 60 c.c. <strong>of</strong> spirit, contained in a distilling flask and cooled<br />
in ice, 42 c.c. <strong>of</strong> concentrated hydrochloric acid are gradually added<br />
drop by drop. During the addition <strong>of</strong> the acid the flask is shaken.<br />
The flask is then attached to an efficient condenser, through which<br />
ice-water may be run with advantage ; the receiver (a filter flask)<br />
should stand in a freezing mixture. After addition <strong>of</strong> the acid the<br />
ethyl nitrite is distilled by heating the flask first at 25°, finally at<br />
40°, in a basin <strong>of</strong> warm water. After being dried for a short time<br />
over potassium carbonate the product is sufficiently pure for most
148 ETHYL NITEATB<br />
purposes and, because <strong>of</strong> its great volatility (boiling point 17°), is<br />
best used immediately.<br />
Experiment.—A few drops <strong>of</strong> amyl or ethyl nitrite are shaken<br />
with dilute potassium iodide solution. No brown colour should be<br />
produced. Addition <strong>of</strong> a drop <strong>of</strong> dilute hydrochloric acid leads, in a<br />
few seconds, to a copious liberation <strong>of</strong> iodine.<br />
(c) ETHYL NITRATE 1<br />
Concentrated nitric acid (d. 1-4, 250 c.c.) is boiled with 30 g. <strong>of</strong><br />
urea nitrate. After the solution has been cooled one half is poured<br />
into a tubulated retort containing 30 g. <strong>of</strong> urea nitrate and 150 c.c.<br />
<strong>of</strong> alcohol. A moderate-sized condenser is attached to the retort,<br />
which is then carefully heated on a sand bath. After about one<br />
third <strong>of</strong> the material has been distilled the remainder <strong>of</strong> the boiled<br />
urea nitrate-nitric acid solution, mixed with 100 c.c. <strong>of</strong> alcohol, is<br />
allowed to run slowly into the retort from a dropping funnel inserted<br />
through the tubulure. The operation must be carried out without<br />
interruption: the mixture <strong>of</strong> alcohol and nitric acid must not be<br />
allowed to stand for any length <strong>of</strong> time. When all the liquid in the<br />
funnel has been added and that in the retort has been reduced by<br />
distillation to 50-100 c.c, the ethyl nitrate which has passed over<br />
is freed from alcohol by being shaken in a separating funnel twice<br />
with water, then once with dilute sodium carbonate solution, and<br />
finally once more with water (ethyl nitrate is heavier than water !).<br />
After being dried over calcium chloride it is distilled from a water<br />
bath in which the distilling flask should be immersed. Boiling<br />
point <strong>of</strong> ethyl nitrate 86°. (Goggles should be worn in this experiment.)<br />
The use <strong>of</strong> ethyl nitrate in the preparation <strong>of</strong> phenylnitromethane<br />
is described later (Chap. VI. 8, p. 256).<br />
When ethyl nitrate is rapidly heated, for example in a flame, it<br />
decomposes explosively; it belongs to the same class <strong>of</strong> substances<br />
as nitroglycerine. Precautions should therefore be taken. Under the<br />
conditions employed ethyl alcohol is not oxidised by pure nitric acid<br />
but merely esterified. Oxidation sets in immediately if traces <strong>of</strong> nitrous<br />
acid are present. Since the nitric oxide which is thus produced from<br />
the nitrous acid is at once oxidised to NO2 by the nitric acid, the oxidation,<br />
which is initially slight, becomes progressively greater, its velocity<br />
1 Lossen, Annalen, 1868, supplementary vol. 6, 220.
SAPONIFICATION 149<br />
increases continuously as a result <strong>of</strong> the heat produced in the reaction,<br />
and it finally proceeds violently and almost explosively. Reactions<br />
<strong>of</strong> this type, in which the velocity is progressively increased by their<br />
own intermediate products, are said to be " autocatalytic ".<br />
The first product <strong>of</strong> the oxidation <strong>of</strong> alcohol is acetaldehyde and an<br />
important end-product is fulminic acid, which latter can, however,<br />
only be isolated if silver or mercury ions are present. With these ions<br />
it forms salts—fulminates—which are stable towards nitric acid; in<br />
them, it must be presumed, the linkage with the metal is homopolar<br />
and non-ionogenic, as in mercuric cyanide. The formation <strong>of</strong> fulminic<br />
acid takes place because the carbonyl group <strong>of</strong> the aldehyde confers<br />
reactivity on the adjacent methyl group which then forms a point <strong>of</strong><br />
attack for the nitrous acid. The various stages in the process are<br />
indicated by the following formulae :<br />
HC.CHO HC.COOH O2N.C.COOH<br />
H3C.CHO —• || —• || —• ||<br />
NOH NOH HON<br />
O,N,<br />
3=N0H + CO, —y C=NOH + HNOo.<br />
The nitrous acid here acts on the alcohol in the same way as do the<br />
halogens in the production <strong>of</strong> chlor<strong>of</strong>orm and iod<strong>of</strong>orm.<br />
(d) HYDROLYSIS OF A FAT OE VEGETABLE OIL<br />
Of any fat or oil 600 g. (about 0-66 mole) are hydrolysed with<br />
600 c.c. <strong>of</strong> approximately 5 2V-sodium hydroxide solution.<br />
The fat is poured into a warm mixture <strong>of</strong> 100 c.c. <strong>of</strong> the sodium<br />
hydroxide solution and 100 c.c. <strong>of</strong> water. After one hour another<br />
150 c.c. <strong>of</strong> hydroxide solution are added, and again one hour later<br />
200 c.c. <strong>of</strong> the solution and 200 c.c. <strong>of</strong> water. The mixture must be<br />
frequently shaken and should be warmed to gentle boiling only.<br />
After a further period <strong>of</strong> four hours the remainder <strong>of</strong> the hydroxide<br />
solution is added ; if necessary, water is first added to replace that<br />
lost by evaporation. Again after one hour half a litre <strong>of</strong> water is<br />
added and boiling is continued until a thick homogeneous mass is<br />
produced (about two to three hours). Then 3-4 litres <strong>of</strong> hot water<br />
are poured in with vigorous stirring. A thick transparent gum is<br />
thus formed. Finally the soap is salted out at 100° by the addition<br />
<strong>of</strong> 200 g. <strong>of</strong> common salt and the mixture is left to stand over night.<br />
The whole operation is best carried out in a large enamelled pot<br />
because <strong>of</strong> the voluminous froth produced.
150 GLYCEKOL<br />
Next morning, when the material has cooled, the solid cake <strong>of</strong><br />
soap is lifted out and washed to remove adherent alkali. It may be<br />
cut into small pieces by means <strong>of</strong> a thin wire and then left to dry for<br />
several weeks.<br />
The sodium salts <strong>of</strong> the higher fatty acids are sparingly soluble in<br />
cold water but more readily in hot. Dissolve a small piece <strong>of</strong> soap in<br />
the minimum amount <strong>of</strong> boiling water in a beaker and allow the<br />
solution to cool: a stiff jelly is formed.<br />
To purify the soap 20-30 g. are dissolved in boiling water, salted<br />
out from the hot solution, and again allowed to solidify. In this way<br />
the small amount <strong>of</strong> alkali in the crude product is removed. The<br />
soap, however, remains alkaline to litmus and turmeric papers. The<br />
hydrolysis <strong>of</strong> the quite pure soap is, however, not sufficiently extensive,<br />
the concentration <strong>of</strong> OH-ions not sufficiently large, for<br />
phenolphthalein to be coloured.<br />
Preparation <strong>of</strong> the Free Fatty Acids.—About 150 g. <strong>of</strong> the crude<br />
moist soap in a litre <strong>of</strong> water are heated almost to boiling. With<br />
vigorous stirring 2 2V-sulphuric acid is added, until the solution is<br />
distinctly acid to Congo paper and the mixture <strong>of</strong> fatty acids has<br />
separated as a supernatant oily layer. If the original fat was solid<br />
this layer solidifies after standing in the cold for some time. The<br />
cake is lifted out, melted once again with a little water in a small<br />
beaker on the water bath, and, after it has again solidified, the acids<br />
are distilled in vacuo. Boiling point 220°-225°/12 mm.<br />
If an oil is hydrolysed the soap obtained is less solid and the<br />
acids crystallise only partially. (Why ?) In this case they are<br />
dissolved in ether and worked up in the usual way.<br />
Glycerol.—The glycerol remains in the brown liquor from which<br />
the soap has been taken. This liquor is first accurately neutralised<br />
(to Congo paper) with hydrochloric acid, shaken with animal charcoal<br />
in order to remove precipitated fatty acids, 1 filtered through a<br />
folded filter paper, and then concentrated in vacuo in the apparatus<br />
shown on p. 31. When after some time sodium chloride separates<br />
the capillary tube sometimes fails to act, and the concentration is<br />
continued on the water bath. The highly concentrated solution is<br />
filtered at the pump from the sodium chloride, which is washed with<br />
a little alcohol, and the filtrate is again concentrated in a Claisen<br />
flask till almost quite free from water. The residue is digested with<br />
150 c.c. <strong>of</strong> alcohol and filtered through a small Buchner funnel;<br />
1 Clarification with animal charcoal is <strong>of</strong>ten unnecessary.
IODINE AND SAPONIFICATION VALUES 151<br />
the material on the filter is then washed with 50 c.c. <strong>of</strong> alcohol.<br />
The alcoholic solution thus obtained is concentrated as far as possible<br />
on the water bath and is then washed into a Claisen flask with a<br />
little alcohol. When the contents <strong>of</strong> the flask are distilled in<br />
vacuo alcohol and water, and then glycerol pass over. The bulk <strong>of</strong><br />
the glycerol is collected between 180° and 195°/13 mm. Yield<br />
about 35 g.<br />
In order to obtain the glycerol quite pure and anhydrous the<br />
distillation must be repeated.<br />
Analysis <strong>of</strong> Fats.—The " iodine value " <strong>of</strong> a fat or oil is a quantitative<br />
measure <strong>of</strong> the number <strong>of</strong> carbon-carbon double bonds which it<br />
contains. This number is the amount <strong>of</strong> iodine in grammes which combines<br />
chemically with 100 g. <strong>of</strong> the fat or oil. Nowadays the number<br />
<strong>of</strong> double bonds in organic compounds is usually determined with perbenzoic<br />
acid (cf. p. 111).<br />
Determination <strong>of</strong> the Iodine Value.—Pure iodine (2-5 g.) and mercuric<br />
chloride (3 g.) are each dissolved in 50 c.c. <strong>of</strong> pure spirit and the<br />
clear solutions are mixed. After twelve hours the iodine titre <strong>of</strong> the<br />
mixture is determined in a 10 c.c. portion by adding 10 o.c. <strong>of</strong> 10 per<br />
cent potassium iodide solution and titrating with 0-1 N-thiosulphate<br />
solution.<br />
The fat to be examined (0-5-0-7 g.) is dissolved in 15 c.c. <strong>of</strong> chlor<strong>of</strong>orm<br />
in a dry conical flask (capacity 500 c.c.) and 25 c.c. <strong>of</strong> the standardised<br />
iodine solution are added. If, after a short time, the colour <strong>of</strong> the<br />
solution diminishes to a light brown, it is necessary to add a further<br />
10 c.c. <strong>of</strong> the iodine solution. After four hours the colour <strong>of</strong> the solution<br />
should still be dark brown. Potassium iodide solution (20 c.c. <strong>of</strong> 10<br />
per cent solution) is now added and the uncombined iodine still present<br />
titrated as above. The calculation is made in accordance with the<br />
definition <strong>of</strong> " iodine value". Lard, olive oil, or linseed oil should be<br />
examined.<br />
To determine the saponification value x <strong>of</strong> a fat 0-5-1-0 g. is boiled<br />
under reflux condenser for half an hour with 10 c.c. <strong>of</strong> O-SiV-alcoholic<br />
KOH solution and the excess <strong>of</strong> alkali is then titrated with 0-5 N-HCl,<br />
and phenolphthalein as indicator.<br />
The method is a general one and can be applied to esters to determine<br />
the equivalent <strong>of</strong> an acid combined in them. Ester equivalent =<br />
a. 1000/6 where a is the weight <strong>of</strong> ester taken (in grammes) and b is<br />
the number <strong>of</strong> c.c. <strong>of</strong> N-alkali used up.<br />
Linseed oil is the most important <strong>of</strong> the so-called " drying " oils.<br />
These oils contain highly unsaturated acids, such as linolenic C17H29,<br />
CO2H and linolio acid C17H31.CO2H, and are therefore able to combine<br />
1 The number <strong>of</strong> milligrammes <strong>of</strong> KOH which is used up by 1 g. <strong>of</strong> fat.
152 THE HOFMANN DEGKADATION<br />
directly with, the oxygen <strong>of</strong> the air, forming solid peroxides and their<br />
transformation products. Oleic acid cannot act in the same way. Olive<br />
oil and sesame oil, for example, do not " dry ". Linseed oil is used as a<br />
medium in oil painting and in the manufacture <strong>of</strong> varnishes.<br />
8. DESCENDING A HOMOLOGOUS SERIES. CONVERSION OF<br />
CARBOXYLIC ACIDS INTO THE NEXT LOWER AMINES<br />
(a) THE HOFMANN REACTION. METHYLAMINE FROM<br />
ACETAMIDE X<br />
A mixture <strong>of</strong> acetamide (30 g. =0-5 mole) and bromine (80 g. = 26<br />
c.c.) in a half-litre flask is kept well cooled with water while enough<br />
<strong>of</strong> a solution <strong>of</strong> 50 g. <strong>of</strong> potassium hydroxide in 350 c.c. <strong>of</strong> water is<br />
added to change the initially red-brown colour into a pale yellow;<br />
this requires most <strong>of</strong> the alkali. The solution is now run from a<br />
dropping funnel in an unbroken jet into a solution <strong>of</strong> 80 g. <strong>of</strong><br />
potassium hydroxide in 150 c.c. <strong>of</strong> water, maintained at 70°-75°<br />
in a litre flask. The operation lasts for several minutes. Until the<br />
reaction mixture becomes colourless (one quarter to half an hour)<br />
the temperature is maintained at 70°-75°, and then the methylamine<br />
is distilled with steam. An adapter is fixed to the lower end <strong>of</strong> the<br />
condenser and dips 1 cm. below the surface <strong>of</strong> the liquid in the receiver<br />
(100 c.c. <strong>of</strong> approximately 5 iV-hydrochloric acid 2 ). As soon<br />
as the liquid which forms in the condenser is no longer alkaline the<br />
distillation is discontinued and the contents <strong>of</strong> the receiver are<br />
evaporated to dryness in a porcelain basin on the water bath. The<br />
last traces <strong>of</strong> water are removed by allowing the basin to stand over<br />
night in a vacuum desiccator. The dried material is boiled with<br />
absolute alcohol, which dissolves the methylamine hydrochloride<br />
but not the ammonium chloride with which it is mixed. The clear<br />
nitrate obtained when the ammonium chloride is removed by filtration<br />
is concentrated to a small volume and the methylamine hydrochloride<br />
is allowed to crystallise out in the cold. The salt is filtered<br />
with suction, washed with a little alcohol, and dried in a desiccator.<br />
Yield 15-20 g.<br />
The isonitrile reaction (p. 167) should be carried out with this<br />
salt, and its behaviour on warming with a little nitrite in faintly acid<br />
aqueous solution should be examined.<br />
1 Ber., 1882, 15, 762 ; 1884, 17, 1406, 1920.<br />
2 50 c.c. <strong>of</strong> cone, hydrochloric acid and 50 c.c. <strong>of</strong> water.
THE CUETIUS KEACTION 153<br />
(b) THE CUETIUS EEACTION PHENYL CYANATE<br />
Benzhydrazide. 1 —24 g (0 15 mole) <strong>of</strong> ethyl benzoate (p 141) are<br />
heated for six hours under a small reflux condenser on the water bath<br />
with 9 g <strong>of</strong> hydrazme hydrate 2 The solid crystalline cake which is<br />
formed on cooling is, after some time, filtered as dry as possible at the<br />
pump and washed with a little ice-cold methyl alcohol If the yield<br />
is too small the filtrate is concentrated and heated agam<br />
The crude product (16-18 g) is sufficiently pure for further<br />
treatment A sample can be recrystalhsed from hot water or from<br />
a little alcohol Melting point 112°<br />
Benzoylazide. 3 —14 g (0 1 mole) <strong>of</strong> the dry hydrazide are made<br />
into a clear solution with 200 c c <strong>of</strong> approximately 2V-hydrochlonc<br />
acid in a filter jar (capacity 0 5 1) The solution is cooled in ice and<br />
stirred, while 8 g <strong>of</strong> sodium nitrite m 50 c c <strong>of</strong> water are added An<br />
immediate reaction takes place and the azide separates in crystalline<br />
form When a filtered sample <strong>of</strong> the solution is no longer made<br />
turbid by the addition <strong>of</strong> a drop <strong>of</strong> nitrite solution, the precipitate<br />
is filtered dry at the pump, washed well with water, and dried,<br />
first on porous plate and then in a vacuum desiccator over concentrated<br />
sulphuric acid and potassium hydroxide Yield 14 g<br />
Phenyl Cyanate. 4 —The azide used for the preparation <strong>of</strong> the<br />
cyamc ester must be absolutely dry Test for constant weight on a<br />
good hand balance<br />
Since benzoylazide explodes when rapidly heated or when in contact<br />
with concentrated sulphuric acid, it must be handled carefully Goggles<br />
must be worn until the distillation <strong>of</strong> the phenyl cyanate has been<br />
completed<br />
The distillation <strong>of</strong> the end-product is carried out m the flask<br />
which is used for the decomposition, a Claisen flask <strong>of</strong> capacity<br />
75-100 c c is suitable A capillary tube and a thermometer are got<br />
ready before the decomposition <strong>of</strong> the azide is carried out All the<br />
apparatus must be thoroughly dry<br />
The Claisen flask is fixed in an inclined position and a small<br />
condenser jacket is slipped over the side tube, which slopes upwards<br />
Atmospheric moisture is excluded by fixing a calcium chloride tube<br />
to the upper end <strong>of</strong> the side tube Benzoylazide (12 g ) and benzene<br />
1<br />
T Curtius, J pr Chem , 1894, 50, 295<br />
2<br />
This can be obtained cheaply from the firm <strong>of</strong> Dr F Raschig, Ludwigshafen<br />
am Rhem 3 l<br />
T Curtius, Ber , 1890, 23, 3029 G Schroeter, Ber , 1909, 42, 2339
154 THE CUETIUS KEACTION<br />
(40 c.c. ; dried over sodium) are placed in the flask, which is slowly<br />
heated to 60°-70° in a basin <strong>of</strong> water. The flask must not be in<br />
contact with the bottom <strong>of</strong> the basin. When the vigorous evolution<br />
<strong>of</strong> nitrogen which sets in has slackened, the temperature is raised to<br />
about 80°. The flask is then cooled and adjusted for vacuum distillation.<br />
The benzene is first distilled at ordinary pressure from the<br />
boiling water bath. Then the bath is cooled and the phenyl cyanate<br />
is distilled at 20-25 mm. pressure. Boiling point 60°/20 mm.<br />
Yield 7-8 g.<br />
The distillate, which should be colourless, must be immediately<br />
transferred to a tight vessel (preferably to a sealed tube) after making<br />
the following two tests. A few drops are poured into a little water.<br />
The crystalline substance formed is diphenylurea. How is it produced<br />
?<br />
Phenylurethane.—Another portion is poured into alcohol and the<br />
solution is evaporated to dryness.<br />
The portion <strong>of</strong> azide which was not used for conversion to cyanate<br />
(about 2 g.) is boiled for half an hour under reflux condenser with<br />
5 c.c. <strong>of</strong> absolute alcohol. 1 On concentrating the solution, phenylurethane<br />
likewise separates. Melting point 52°.<br />
The decomposition <strong>of</strong> methanes into amine, CO2, and alcohol is<br />
usually carried out with hydrochloric acid in sealed tubes. Decomposition<br />
by distillation with calcium hydroxide is more convenient,<br />
but gives a poorer yield.<br />
The phenylurethane which has been obtained is mixed with three<br />
times its weight <strong>of</strong> slaked lime and cautiously distilled from a small<br />
retort. The aniline which passes over can, with a little skill, be<br />
redistilled from a small flask, but in any case it should be identified<br />
by conversion into acetanilide and by the bleaching powder reaction.<br />
In the determination <strong>of</strong> constitution it is <strong>of</strong>ten necessary to remove<br />
carboxyl groups (such, as are formed by oxidation, for example) and so<br />
to break down the molecule. The simplest method <strong>of</strong> doing this, namely,<br />
removal <strong>of</strong> carbon dioxide by distillation <strong>of</strong> a salt with soda-lime :<br />
R.COONa + NaOH —> RH + Na2CO3,<br />
generally does not proceed smoothly and leads, moreover, to a hydrocarbon<br />
unsuitable for further reactions.<br />
Hence the great preparative importance <strong>of</strong> the two related methods<br />
for the degradation <strong>of</strong> acids, due to H<strong>of</strong>mann and to Curtius, and<br />
starting respectively from the amide and the hydrazide.<br />
1 T. Curtius, Ber., 1894, 27, 779.
THE HOFMANN AND CURTIUS EBACTIONS 155<br />
Both, processes furnish, the primary amine corresponding to the next<br />
lower homologue <strong>of</strong> the series, and both lead to this result by way <strong>of</strong> the<br />
same intermediate product, namely, the cyanic ester.<br />
By the action <strong>of</strong> hypobromite on the —-CONH2-group one hydrogen<br />
atom <strong>of</strong> the NH2-group is replaced by bromine. The first product <strong>of</strong><br />
the H<strong>of</strong>mann reaction, the N-bromoamide, can be isolated in certain<br />
cases.<br />
By the action <strong>of</strong> alkali the bromoamide loses HBr, and the transient<br />
radicle which is thus formed undergoes rearrangement to a cyanic ester<br />
which, under the experimental conditions <strong>of</strong> the reaction, is decomposed<br />
into a primary amine and CO2:<br />
R.C:O<br />
| —<br />
NH2<br />
R.C:O<br />
HNBr<br />
R.C:O<br />
_ A _<br />
—>• RN;C:O —•> R.NH, + C0<br />
In this way acetamide furnishes meihylamine, benzamide yields<br />
aniline, and urea, albeit in small amount, forms hydrazine.<br />
Hydroxamic acids are transformed in a similar way by loss <strong>of</strong> water<br />
into cyanates and so into amines.<br />
The reaction <strong>of</strong> Curtius, which is especially to be preferred in the<br />
case <strong>of</strong> the higher members on account <strong>of</strong> the favourable solubilities<br />
<strong>of</strong> the intermediate products, involves as its first stage the preparation<br />
<strong>of</strong> the hydrazide from an ester (or acid chloride). The hydrazide is<br />
then converted, usually very readily, by the action <strong>of</strong> nitrous acid into<br />
the azide. In many cases it is more convenient to prepare the azide by<br />
treating an acid chloride with sodium azide previously activated with<br />
hydrazine hydrate. 1 Azides easily undergo thermal decomposition, the<br />
two " azo " nitrogen atoms being eliminated as elementary nitrogen.<br />
In this way, however, the same radicle is formed as was invoked above to<br />
explain the H<strong>of</strong>mann reaction :<br />
R.C:O<br />
R.C:O<br />
N<br />
A<br />
-N,<br />
—> RN:C:O .<br />
HN.NH,<br />
N<br />
A<br />
N-N<br />
Curtius usually decomposed the azides in alcohol, which at once<br />
explains the formation <strong>of</strong> urethanes; these, by vigorous hydrolysis,<br />
decompose into primary amine, CO2, and alcohol.<br />
An important application <strong>of</strong> the H<strong>of</strong>mann reaction occurs in the<br />
first technical synthesis <strong>of</strong> indigo and consists in the degradation <strong>of</strong><br />
phthalimide to anthranilic acid. See p. 372.<br />
1<br />
J. Nelles, Ber., 1932, 65, 1345.
CHAPTBE III<br />
NITRO-COMPOUNDS AND THEIR REDUCTION PRODUCTS<br />
1. NITROMETHANE 1<br />
CHLOROACETIC acid (94 g.) dissolved in 200 c.c. <strong>of</strong> water in a wide<br />
beaker is accurately neutralised with 53 g. <strong>of</strong> anhydrous sodium<br />
carbonate, and 75 g. <strong>of</strong> sodium nitrite dissolved in 120 c.c. <strong>of</strong> water<br />
are then added. About 100 c.c. <strong>of</strong> the mixture thus obtained are<br />
transferred to a round-bottomed flask (capacity 750 c.c.) which is<br />
fitted with a dropping funnel and is connected to a downward<br />
condenser. The flask is now strongly heated in a conical air bath<br />
or on a wire gauze (raise the temperature slowly). A vigorous<br />
reaction sets in with evolution <strong>of</strong> CO2 even before boiling begins.<br />
By allowing the remainder <strong>of</strong> the solution to run slowly into the<br />
boiling liquid the reaction is maintained, but is not allowed to become<br />
too vigorous. The nitromethane distils with the steam and forms<br />
the heavier layer in the receiver. As soon as drops <strong>of</strong> oil no longer<br />
pass over, the receiver is changed and a further 100 c.c. <strong>of</strong> water containing<br />
dissolved nitromethane are collected separately. The nitromethane<br />
is separated from the first distillate and the aqueous layer<br />
<strong>of</strong> the latter is combined with the second distillate. The combined<br />
solution is saturated with sodium chloride (35 g. for each 100 c.c.)<br />
and again subjected to distillation; about a quarter <strong>of</strong> the whole<br />
volume is collected. Then a clear distillate again passes over.<br />
The nitromethane in this second distillate is separated from the<br />
water, combined with the material first obtained, thoroughly dried<br />
over calcium chloride, and then distilled. Boiling point 101°. Yield<br />
20-24 g. (30-36 per cent <strong>of</strong> theoretical).<br />
Nitromethane is the most easily accessible aliphatic nitro-compound<br />
; Kolbe's method <strong>of</strong> preparation is much less satisfactory when<br />
applied to higher members <strong>of</strong> the series. The course <strong>of</strong> the reaction is<br />
clear, and the reasons for the decomposition which takes place are similar<br />
1 H. Kolbe, J. pr. Chem., 1872, 5, 429; Steinkopf, Ber., 1909, 42, 3438.<br />
156
NITEOMETHANB 157<br />
to those used to explain the decomposition <strong>of</strong> malonic acid : the nitroaoetic<br />
acid first formed decomposes into CH3NO2 and CO2. Other<br />
nitroparaffins are usually obtained by the method discovered by<br />
V. Meyer—by the action <strong>of</strong> silver nitrite on alkyl iodides. The method<br />
<strong>of</strong> Konovalov—heating in a sealed tube to 120°-l30° with very dilute<br />
nitric acid—is <strong>of</strong>ten successful in the case <strong>of</strong> saturated hydrocarbons,<br />
particularly those <strong>of</strong> the hydroaromatic series. Phenylnitromethane<br />
is discussed in Chap. VI. 8, pp. 256, 257. Recall the isomerism with the<br />
alkyl nitrites. How do the reactions <strong>of</strong> the two classes <strong>of</strong> compounds<br />
differ ?<br />
The primary and secondary nitroparaffins are neutral substances,<br />
but are transformed by alkalis into salts <strong>of</strong> isomeric aci- forms<br />
(Hantzsch):<br />
R R<br />
\>CHNO2 \<br />
—> >C=N=O.<br />
This change is more fully discussed in the section on tautomerism<br />
on p. 257.<br />
Experiment.—Dissolve 1 c.c. <strong>of</strong> nitromethane in water and test<br />
the solution with litmus paper. Then add some phenolphthalein<br />
and, drop by drop from a burette, 0-1 2V-sodium hydroxide solution.<br />
Before a permanent pink colour develops about 2 c.c. <strong>of</strong> the alkali<br />
will be added—a sign that an acid, ad-nitromethane, H2C : NOOH,<br />
has been formed from the neutral nitromethane. A small sample <strong>of</strong><br />
this solution gives with ferric chloride a blood-red colour, characteristic<br />
<strong>of</strong> act-nitro-compounds. The salts <strong>of</strong> the act-compound undergo<br />
extensive hydrolysis. This is shown by further addition <strong>of</strong> 0-1 Nalkali<br />
which produces a deep red colour. If 10 c.c. <strong>of</strong> alkali were<br />
added and 5 c.c. <strong>of</strong> 0-1 2V-hydrochloric acid are now run in the solution<br />
is decolorised because the liberated act-compound restricts<br />
the hydrolysis <strong>of</strong> its salt. But the conversion <strong>of</strong> H2C : N02H into<br />
H3C.NO2 proceeds so rapidly that the red colour reappears in a few<br />
moments.<br />
When the nitroparaffins are reduced with powerful agents, the<br />
corresponding amines are formed in a way similar to that described<br />
in the next section for nitrobenzene. But just as in the case <strong>of</strong> nitrobenzene,<br />
so also with nitroparaffins, the reaction can be stopped at the<br />
hydroxylamine stage by using zinc dust in a neutral medium.<br />
Experiment.—To a few drops <strong>of</strong> nitromethane dissolved in a<br />
little water some pieces <strong>of</strong> granulated zinc and then some concentrated<br />
hydrochloric acid are added. A vigorous reaction takes
158 MBTHYLHYDEOXYLAMINB<br />
place. When this has subsided the mixture is heated for a short<br />
time on the water bath and then the liquid is decanted. When a<br />
large excess <strong>of</strong> concentrated caustic alkali is added it is possible to<br />
recognise, by the odour produced and by the fact that turmeric<br />
paper is turned brown, the formation <strong>of</strong> a volatile amine. If it is<br />
desired to use the reaction for the preparation <strong>of</strong> methylamine the<br />
nitromethane must be added to the reducing mixture in small<br />
portions. Compare also p. 152.<br />
iV^Methylhydroxylamine.—An aqueous solution <strong>of</strong> nitromethane<br />
is mixed with about its own weight <strong>of</strong> ammonium chloride, the<br />
mixture is then cooled (temperature about 10°) and three parts <strong>of</strong><br />
zinc dust are added in small portions with constant shaking. Zinc<br />
dust is now removed by nitration, and it is found that the filtrate<br />
reduces ammoniacal silver and Fehling's solutions. The preparation<br />
<strong>of</strong> this easily accessible alkylhydroxylamine as hydrochloride is<br />
described by Beckmann, Annalen, 1909, 365, 204.<br />
Almost without exception the numerous transformations which,<br />
primary and secondary nitroparaffins undergo involve the act-form, i.e.<br />
they take place under conditions in which the salt <strong>of</strong> the act-form is<br />
produced. Qualitatively the nitroparaffins greatly resemble ketones in<br />
their mode <strong>of</strong> action, although the much greater reaction velocity <strong>of</strong><br />
the nitro-compounds brings about a quantitative difference.<br />
1. By the action <strong>of</strong> bromine bromonitro-compounds are formed, e.g.<br />
H2C=N=O _ rH2C—N=O ~i H2C—NO2<br />
| J \ | |\ —• | +NaBr.<br />
ONa L Br Br ONaJ Br<br />
2. Nitrous acid converts primary nitroparaffins into nitrolic acids<br />
and the secondary ones into so-called pseudonitroles, which latter, being<br />
nitroso-compounds, are coloured green or blue :<br />
(a) H2C=N=O rH2C—N=O n HC—NO2 + H2O<br />
| +H0N0 —• | |\ —*||<br />
OH L NOOHOHJ N( [OH<br />
CH3.C.CH3 +H0N0<br />
O=N—OH ~ ~*<br />
CH..C.CH.<br />
NO<br />
O=N< OH<br />
OH<br />
CH..C.CH 3<br />
NO, NO<br />
+ H.O.<br />
Experiment.—Methylnitrolic acid. 1 —Nitromethane (3-2 g.) is<br />
dissolved in 30 c.c. <strong>of</strong> ice-cold 2 iV-sodium hydroxide solution and a<br />
1 Ber., 1909, 42, 808.
SILVBE FULMINATE 159<br />
concentrated solution <strong>of</strong> sodium nitrite (3-5 g.) is added. Without<br />
further cooling 4 2\f-sulphuric acid is run in from a dropping funnel<br />
until the solution, which is at first deep red, has just become yellow<br />
and does not yet turn potassium iodide-starch paper blue. The<br />
mixture is now extracted twice with ether and the aqueous layer is<br />
again cooled. Sulphuric acid is again dropped in until the evolution<br />
<strong>of</strong> nitrous acid becomes distinct and the solution is then again made<br />
so strongly alkaline with 52V-sodium hydroxide solution, that a<br />
deep orange colour results. Once more the solution is acidified to<br />
such an extent that nitrous acid cannot yet be detected, and is again<br />
extracted twice with ether. The combined etKer extracts are dried<br />
for two hours over calcium chloride in a vessel kept on ice. The<br />
ethereal solution is now transferred to a small round flask and the<br />
solvent removed by distillation with a capillary in vacuo on the water<br />
bath at 15°-20°. A residue consisting <strong>of</strong> about 1 g. <strong>of</strong> well-crystallised<br />
pale yellow methylnitrolic acid remains. The preparation decomposes<br />
in the course <strong>of</strong> a few hours. Test its behaviour towards<br />
alkalis.<br />
Silver Fulminate. 1 —Freshly-prepared methylnitrolic acid (0-5 g.)<br />
dissolved in 4 c.c. <strong>of</strong> water is heated to boiling in a wide test tube over<br />
a naked flame with 1 c.c. <strong>of</strong> 52V-nitric acid (concentrated nitric acid<br />
<strong>of</strong> density 1-4 diluted with an equal volume <strong>of</strong> water) and 4 c.c. <strong>of</strong><br />
10 per cent silver nitrate solution. After a short time the reaction<br />
begins, a vigorous evolution <strong>of</strong> gas (NO) occurs, and crystalline<br />
silver fulminate is precipitated. Boiling is continued for a few<br />
minutes longer with constant shaking. The mixture is then cooled<br />
and the product filtered at the pump and washed with water. On a<br />
small piece <strong>of</strong> porous plate a small sample weighing about 10 mg. is<br />
dried without rubbing and its shattering power is tested in the flame<br />
and under a blow from a hammer. (Wear goggles.)<br />
While still moist the bulk <strong>of</strong> the material is transferred to a test<br />
tube ; even in the moist condition pressing with a metal spatula or<br />
other hard object is to be avoided. Then 2 c.c. <strong>of</strong> concentrated<br />
hydrochloric acid are poured into the test tube, when the odour <strong>of</strong><br />
free fulminic acid can be perceived. This odour so closely resembles<br />
that <strong>of</strong> hydrocyanic acid as to make confusion possible. After half<br />
an hour the contents <strong>of</strong> the test tube are heated for a short time in the<br />
boiling water bath, 4 c.c. <strong>of</strong> water are added, silver chloride is<br />
removed by nitration, and the nitrate is evaporated to dryness on<br />
1 Ber., 1907, 40, 419.
160 NITKOLIC ACIDS, PHENYLNITKOETHYLENE<br />
the water bath in a small glass dish. The hydroxylamine hydrochloride<br />
constituting the residue is recognised by its reducing effect<br />
on ammoniacal silver solution and on Fehling's solution.<br />
Silver fulminate must invariably be destroyed immediately after it is<br />
prepared. This is most readily done with hydrochloric acid.<br />
The nitrolic acids are colourless, but dissolve in alkalis with a deep<br />
red colour because in addition to the chromogenic nitroso-group the<br />
aci-nitro-group is formed. The following formula is ascribed to the<br />
red salt, e.g.<br />
HC=N=O<br />
NOONa<br />
When methylnitrolic acid is heated in nitric acid solution it decomposes<br />
into nitrous and fulminic acids. The latter can be isolated<br />
as silver fulminate if silver nitrate is present.<br />
H \<br />
>C:NOH —y N02H + C:NOH .<br />
O2]SK<br />
The production <strong>of</strong> fulminates (silver and mercury fulminates) from<br />
ethyl alcohol and nitric acid takes place by way <strong>of</strong> methylnitrolic acid.<br />
This question was discussed on p. 149.<br />
The mercuric salt <strong>of</strong> nitromethane decomposes directly into mercury<br />
fulminate and water (Nef).<br />
(H2C = NO2)2Hg — •> (C = NO)2Hg + 2 H2O .<br />
3. Like the ketones the primary nitro-compounds condense with<br />
aldehydes, water being eliminated. Phenylnitroethylene is conveniently<br />
prepared in this way.<br />
C6H5.CHO + H3C.NO2 —> C6H5.CH:CH.NO2.<br />
Phenylnitroethylene. 1 —Nitromethane (3-2 g.) and benzaldehyde<br />
(5-3 g.) are dissolved in 20 c.c. <strong>of</strong> alcohol, and to the solution, which<br />
is well cooled in a freezing mixture and is vigorously shaken, 3-5 g.<br />
<strong>of</strong> potassium hydroxide dissolved in a mixture <strong>of</strong> water (5 c.c.) and<br />
methyl alcohol (10 c.c.) are gradually added. Shaking is continued<br />
until a sample <strong>of</strong> the resulting crystalline paste—occasionally no<br />
crystallisation occurs—forms a clear solution in water. The potassium<br />
salt <strong>of</strong> phenylnitroethyl alcohol, C5H6.CH(OH).CH:NOOK, has<br />
been formed, and the corresponding free acid changes into phenylnitroethylene<br />
with elimination <strong>of</strong> water. The change takes place<br />
1 Thiele and Haeckel, Annalen, 1902, 325, 7; Bouveault and Wahl, Compt.<br />
rend., 1902, 135, 41.
NITKOBENZENE 161<br />
if the reaction product is dissolved in ice-water and 60 c.c. <strong>of</strong> ice-cold<br />
i^-sulphuric acid are run in with stirring. The oil which is formed<br />
soon solidifies and is then filtered with suction, dried on porous plate<br />
for a short time, and recrystallised from little alcohol. About 5 g.<br />
<strong>of</strong> phenylnitroethylene, in the form <strong>of</strong> splendid yellow needles, are<br />
obtained. Melting point 58°.<br />
4. All primary nitro-compounds couple with, diazobenzene, but<br />
instead <strong>of</strong> the expected azo-compounds, phenylhydrazones <strong>of</strong> a-nitroaldehydes<br />
are formed by rearrangement <strong>of</strong> the molecule :<br />
R.C=N=O<br />
HO ONa<br />
H<br />
d: Na<br />
+ HO—N=N.CBHB — R.C—N=O<br />
><br />
3—N02<br />
||<br />
H<br />
+NaOH.<br />
N=N.C6H5<br />
N-NH.C6H5<br />
5. A very interesting reaction <strong>of</strong> nitromethane produced by strong<br />
alkali must also be mentioned here.<br />
Two molecules condense with elimination <strong>of</strong> water to the so-called<br />
meihazonic acid, which has the constitution <strong>of</strong> nitroacetaldoxine (I)<br />
(Meister). 1<br />
2H2C=N=O HC C=N=O HC—CH2.NO2<br />
I - ^ I H | ; (I) ||<br />
ONa NONa ONa NOH<br />
By the action <strong>of</strong> thionyl chloride Steinkopf prepared from this<br />
substance the long-sought nitroacetonitrile 2 NO2.CH2.CN, and by the<br />
hydrolysis <strong>of</strong> this nitrile, nitroacetic acid. 3<br />
2. NITRATION OF AN AROMATIC HYDROCARBON<br />
NITROBENZENE AND DINITEOBENZENE<br />
(a) NITROBENZENE<br />
Concentrated nitric acid (d. 1-4; 100 c.c. = 140 g.) is poured<br />
gradually, with shaking, into a flask (capacity about 0-5 1.) containing<br />
concentrated sulphuric acid (125 c.c. =230 g.). After the warm<br />
mixture has been cooled to room temperature by immersion in cold<br />
1<br />
On the mechanism <strong>of</strong> this reaction, see Annalen, 1925, 444. 15.<br />
2 3<br />
Ber., 1908, 41, 1048.<br />
Ber., 1909, 42, 3925.<br />
M
162 DINITKOBENZENE<br />
water, benzene (90 c.c. = 78 g.; 1 mole) is gradually added with<br />
frequent shaking. If, during the addition, the temperature rises<br />
above 50°-60° the flask is dipped for a short time in ice-water before<br />
further quantities <strong>of</strong> benzene are added. Each time benzene is<br />
added the production <strong>of</strong> a transient intense brown colour is observed.<br />
After the flask has been warmed on the water bath at 60°<br />
under an air condenser for half an hour, the lower layer <strong>of</strong> liquid,<br />
which consists <strong>of</strong> sulphuric and nitric acids, is separated from the<br />
upper layer, which contains the nitrobenzene. 1 The latter is shaken<br />
in a separating funnel, first with water, then with dilute sodium<br />
hydroxide solution, and finally again with water. It must be borne<br />
in mind that the nitrobenzene now forms the lower layer. After<br />
washing and settling, the nitrobenzene is run into a dry flask and<br />
warmed with calcium chloride under an air condenser on the water<br />
bath until the original milkiness has disappeared. Finally, the substance<br />
is purified by distilling (not quite to dryness) from a flask<br />
with air condenser. Boiling point 206°-207°. Yield 100-105 g.<br />
(6) DlNITEOBENZENE<br />
To a mixture <strong>of</strong> 14 c.c. (25 g.) <strong>of</strong> concentrated sulphuric acid<br />
and 10 c.c. (15 g.) <strong>of</strong> fuming nitric acid in an open flask 10 g. <strong>of</strong><br />
nitrobenzene are gradually added (fume chamber). The mixture<br />
is then heated on the water bath for half an hour with frequent<br />
shaking. The reaction mixture is cooled somewhat and then<br />
poured with stirring into cold water. The dinitrobenzene solidifies,<br />
is filtered with suction, washed with water, pressed on porous plate,<br />
and crystallised from alcohol. Melting point 90°. Yield 10-12 g.<br />
The property <strong>of</strong> yielding nitro-derivatives by the action <strong>of</strong> nitric<br />
acid is a characteristic <strong>of</strong> aromatic substances. According to the conditions<br />
under which, the nitration is carried out one or more nitro-groups<br />
can be introduced. Write the equation for the reaction.<br />
If an aromatic compound contains saturated aliphatic side chains<br />
nitration carried out under the above conditions takes place always in<br />
the benzene nucleus and not in the side chain. Since the carbon atoms<br />
<strong>of</strong> benzene are each united directly to only one hydrogen atom, the<br />
nitro-derivatives obtained are tertiary and therefore incapable <strong>of</strong><br />
forming salts, nitrolic acids, or pseudonitroles, as do the primary and<br />
secondary nitro-compounds.<br />
1 In large-scale practice the residual nitrating acid is recovered in a similar<br />
way ; 1-5 moles <strong>of</strong> nitric acid are used in the present case.
METHODS OF NITEATION 163<br />
Nitro-groups can also be introduced into side chains. 1 If toluene<br />
or ethylbenzene, for example, is heated with, dilute nitric acid (d. 1 -076)<br />
in a closed vessel to a temperature somewhat over 100° phenylnitromethane<br />
C6H5.CH2.NO2 or phenylnitroethane C6H5.CH(NO2).CH3 is<br />
obtained.<br />
The same reaction can be applied, not only to the aromatic parent<br />
substances, the hydrocarbons, but also to all their derivatives, such as<br />
phenols, amines, aldehydes, acids, and so on. The nitration does not,<br />
however, always proceed with the same ease, and therefore the most<br />
favourable experimental conditions must be determined for each substance.<br />
If a substance is very easily nitrated it may be done with<br />
nitric acid sufficiently diluted with water, or else the substance to be<br />
nitrated is dissolved in a resistant solvent and is then treated with<br />
nitric acid. Glacial acetic acid is frequently used as the solvent.<br />
Substances which are less easily nitrated are dissolved in concentrated<br />
or fuming nitric acid. If the nitration proceeds with difficulty the<br />
elimination <strong>of</strong> water is facilitated by the addition <strong>of</strong> concentrated<br />
sulphuric acid to ordinary or fuming nitric acid. When nitration is<br />
carried out in sulphuric acid solution, potassium or sodium nitrate is<br />
sometimes used instead <strong>of</strong> nitric acid. The methods <strong>of</strong> nitration described<br />
may be still further modified in two ways : 1, the temperature<br />
or, 2, the amount <strong>of</strong> nitric acid used, may be varied. Thus nitration<br />
can be carried out at the temperature <strong>of</strong> a freezing mixture, at that <strong>of</strong><br />
ice, at that <strong>of</strong> cold water, at a gentle heat, or, finally, at the boiling point.<br />
Moreover, we can either employ an excess <strong>of</strong> nitric acid or the theoretical<br />
amount. Small scale preliminary experiments will indicate which <strong>of</strong><br />
these numerous modifications may be expected to yield the best results.<br />
Since nitro-compounds are usually insoluble or sparingly soluble in water<br />
they can be precipitated from the nitration mixture by dilution with<br />
water.<br />
The chemical character <strong>of</strong> a compound is not fundamentally altered<br />
by the introduction <strong>of</strong> a nitro-group. Thus the ring-substituted nitroderivatives<br />
<strong>of</strong> the hydrocarbons are neutral compounds like the hydrocarbons<br />
themselves. If, however, a nitro-group enters a substance<br />
having, for instance, an acid character, then this character is thereby<br />
intensified ; the nitrophenols, for example, are more acidic than phenol.<br />
Correspondingly, the strength <strong>of</strong> bases is decreased by nitration; the<br />
nitranilines are less basic than aniline.<br />
The great importance <strong>of</strong> the nitro-compounds depends on their<br />
behaviour on reduction. This question is discussed below.<br />
When two nitro-groups are introduced into the benzene ring the<br />
chief product is m-dinitrobenzene, which conforms to the following<br />
general laws <strong>of</strong> substitution. For aromatic compounds there are three<br />
important typical reactions: 1, halogenation; 2, nitration, and 3, sulpho-<br />
1 Konovalov, Ber., 1894, 27, Ref. 194, 468.
164 DIRECTING INFLUENCE OF SUBSTITUENTS<br />
nation. From benzene itself, <strong>of</strong> course, only one mono-halogen-, one<br />
mono-nitro-, or one mono-sulphonic acid derivative can be obtained.<br />
But in a mono-substituted benzene the halogen- or the nitro- or sulphonic<br />
acid group can take up the o-, m-, or y-position. Experiment<br />
has shown that there are two types <strong>of</strong> substitution reaction. In certain<br />
cases the product consists very largely <strong>of</strong> o- and j>- di-substituted<br />
derivatives accompanied by only small amounts <strong>of</strong> m-derivative, whilst<br />
in others the m-derivative predominates and is accompanied by small<br />
quantities only <strong>of</strong> the o- and y-derivatives.<br />
Substituents which direct halogens or nitro- and sulphonic acid<br />
groups—or, indeed, any other group—chiefly to the o- and ^-positions,<br />
are called substituents <strong>of</strong> the first order. Those which direct chiefly<br />
to the m-position are substituents <strong>of</strong> the second order. Those <strong>of</strong> the<br />
first order are : the halogens, alkyl groups, hydroxyl, O-alkyl and<br />
O-acyl groups, the amino-group, etc. Substituents <strong>of</strong> the second order<br />
are : the nitro-group, the sulphonic acid group, the aldehyde group,<br />
the carboxyl, COO-alkyl and CONH2 groups, the CO-alkyl group (in<br />
ketones), the Cfe=N group, etc.<br />
It follows from this enumeration that the substituents <strong>of</strong> the first<br />
order are all, according to the usual view, saturated and contain no<br />
multiple bonds, whereas the opposite holds for the substituents <strong>of</strong> the<br />
second order. It is also noteworthy that o- and ^-substitutions almost<br />
always proceed more easily, i.e. with much greater velocity, than do<br />
m-substitutions.<br />
The difficulty <strong>of</strong> nitration increases progressively with the number<br />
<strong>of</strong> nitro-groups introduced. Already the introduction <strong>of</strong> a second<br />
nitro-group into nitrobenzene requires much more powerful reagents<br />
than the nitration <strong>of</strong> benzene itself. Symmetrical trinitrobenzene is<br />
formed only after several days' boiling <strong>of</strong> the dinitro-compound with<br />
fuming nitric acid and even then only in poor yield.<br />
Compare with this the greater susceptibility to substitution caused<br />
by OH and NH2 and even by the methyl group in toluene. Trinitrotoluene<br />
is manufactured on a large scale as an explosive.<br />
Some <strong>of</strong> the nitro-compounds are liquids, some are solids characterised<br />
by the great readiness with which they crystallise. Those nitrocompounds<br />
which distil without decomposition have higher boiling<br />
points than the parent substances.<br />
If ethylene is treated with nitrating acid, nitroethyl nitrate,<br />
JNTO2.CH2.CH2ONO2 is produced, as has already been mentioned. The<br />
nitroethyl alcohol which is first formed by addition <strong>of</strong> nitric acid is fixed<br />
by esterification, whereas the addition compound with HNO3 which<br />
is first formed at the double bond <strong>of</strong> benzene is decomposed with<br />
elimination <strong>of</strong> H2O for reasons which have been mentioned repeatedly.<br />
This case is therefore analogous to the reactions <strong>of</strong> bromine with<br />
ethylene and with benzene (p. 106).
ANILINE 165<br />
3. REDUCTION OF A NITRO-COMPOUND TO AN AMINE<br />
(a) ANILINE FROM NITROBENZENE 1<br />
To a mixture <strong>of</strong> 120 g. <strong>of</strong> finely granulated tin 2 and 61-5 g.<br />
(0-5 mole) <strong>of</strong> nitrobenzene in a round-bottomed flask (capacity 2 1.),<br />
270 c.c. (320 g.) <strong>of</strong> concentrated hydrochloric acid are added in the<br />
following manner : At first only about one tenth <strong>of</strong> the acid is added,<br />
a moderately wide air condenser is then immediately attached to the<br />
flask and the mixture is shaken. After a short time the contents <strong>of</strong><br />
the flask become warm and eventually begin to boil vigorously.<br />
Without completely suppressing the reaction, the flask is cooled in<br />
water and then the rest <strong>of</strong> the acid is added gradually, with constant<br />
shaking, in such a way that the reaction is always maintained at a<br />
good rate. Finally the mixture is heated on the water bath for one<br />
hour longer, 100 c.c. <strong>of</strong> water are added to the hot solution, and then<br />
a solution <strong>of</strong> 150 g. <strong>of</strong> commercial sodium hydroxide in 200 c.c. <strong>of</strong><br />
water is gradually poured in until the product is strongly alkaline. 3<br />
A long downward condenser is straightway attached to the flask and<br />
steam is passed into the hot liquid until, after the distillate has<br />
ceased to pass over as a milky fluid, a further 300 c.c. <strong>of</strong> clear liquid<br />
have distilled. Finely powdered sodium chloride (25 g. for each<br />
100 c.c.) is dissolved in the distillate and the aniline is then extracted<br />
with ether. 4 The ethereal solution is dried over a few pieces <strong>of</strong> solid<br />
potassium hydroxide, the ether is evaporated, and the aniline is<br />
distilled. Boiling point 184°. Yield 90-100 per cent <strong>of</strong> the<br />
theoretical.<br />
The property <strong>of</strong> being converted by energetic reduction into primary<br />
amines belongs to the nitro-compounds both <strong>of</strong> the aliphatic and <strong>of</strong> the<br />
aromatic series. Six atoms <strong>of</strong> hydrogen are required for the reduction<br />
<strong>of</strong> each nitro-group. In industry nitrobenzene is reduced, not with<br />
expensive tin, but with iron filings or iron powder according to the<br />
old method <strong>of</strong> Bechamp, which is still in use at the present time. The<br />
amount <strong>of</strong> hydrochloric acid indicated by the equation<br />
C6H5.NO2 + 3 Fe + 6 HC1 = C6H5.NH2 + 3 FeCl2 + 2 H2O (A)<br />
1 Annalen, 1842, 44, 283.<br />
8 If granulated tin is not available it may be prepared by melting block-tin<br />
over a blow-pipe in a long-handled iron spoon provided with a spout, and then<br />
pouring the metal drop by drop from a height <strong>of</strong> 2-3 feet into a bucket filled with<br />
water.<br />
3 On the electrolytic removal <strong>of</strong> the tin see p. 317, footnote.<br />
4 On a large scale the salting out is omitted and the " aniline water " is used<br />
in raising the steam for the next batch.
166 KEDUCTION OF NITKO-COMPOUKD TO AMINB<br />
is very much, greater than that actually used on a technical scale.<br />
The process can be carried out with much less, even with about 3 per<br />
cent <strong>of</strong> the quantity calculated from the above equation. This is due<br />
to the fact that the iron is partly oxidised to ferric hydroxide. The<br />
reaction proceeds according to the equation (B) as well as according to<br />
(A), i.e. FeCl2 is continually re-formed.<br />
C6H5.NO2 + 2 FeCl2 + 2 Fe + 4 HaO^C6H5.NH2 + 2 FeCl2 + 2 Fe(OH)3. (B)<br />
Ferric hydroxide is precipitated as a result <strong>of</strong> the hydrolysis <strong>of</strong> the<br />
ferric chloride, and hydrochloric acid is continuously liberated to react<br />
with further quantities <strong>of</strong> iron. The iron oxide ultimately produced<br />
is re-converted into iron powder by hydrogen at red heat, and so becomes<br />
available for the next batch.<br />
Catalytic hydrogenation processes in which copper is the catalytic<br />
agent have also been recently introduced into industrial practice for<br />
the preparation <strong>of</strong> aniline from nitrobenzene.<br />
For the reduction <strong>of</strong> nitro-compounds on a small scale, tin or stannous<br />
chloride and concentrated hydrochloric acid are the most suitable<br />
reagents. Solids are <strong>of</strong>ten difficult to reduce in the absence <strong>of</strong> a solvent<br />
and call for the addition <strong>of</strong> alcohol or glacial acetic acid. When the<br />
addition <strong>of</strong> water to a sample <strong>of</strong> the reaction mixture produces a clear<br />
solution it is known that the reduction is complete. The base will, <strong>of</strong><br />
course, be present as hydrochloride, and hydrochlorides are, almost<br />
without exception, soluble in water. It should be noted, however,<br />
that sparingly soluble double salts with stannous chloride are <strong>of</strong>ten<br />
formed, but these double salts are usually soluble in boiling water.<br />
If a double salt crystallises out in large amounts it is collected at<br />
the pump and is decomposed with alkali or, better, with hydrogen<br />
sulphide ; thus the base is easily obtained in the pure state.<br />
Of the primary monoamines, some, such as .aniline, o-toluidine,<br />
xylidine, are colourless liquids. Others, such as y-toluidine, pseudocumidine<br />
and the naphthylamines, are solids. They can be distilled<br />
without decomposition and are volatile with steam. In water they are<br />
rather sparingly soluble—a 3 per cent solution <strong>of</strong> aniline can be made.<br />
The di- and polyamines are usually solids, not volatile in steam and<br />
much more soluble in water than the monoamines. The amines are<br />
basic in character, but, as a result <strong>of</strong> the negative nature <strong>of</strong> the phenylgroup,<br />
the aromatic amines are considerably weaker bases than are the<br />
aliphatic amines. Consequently aqueous solutions <strong>of</strong> the (stoicheiometrically)<br />
neutral aniline salts are acid to litmus because <strong>of</strong> the hydrolysis<br />
which they undergo. For the same reason a small amount <strong>of</strong> the<br />
free base can be extracted with ether from an aqueous solution <strong>of</strong> an<br />
aniline salt. (Test with a solution <strong>of</strong> hydrogen chloride in ether or,<br />
after evaporation <strong>of</strong> the ether, by the reaction with bleaching powder.)<br />
Experiments.—1. 10 c.c. <strong>of</strong> aniline water (obtained by shaking
KEACTIONS OF ANILINE 167<br />
three drops <strong>of</strong> aniline with 10 c.c. <strong>of</strong> water in a test tube) are diluted<br />
with 100 c.c. <strong>of</strong> water and a small quantity <strong>of</strong> a filtered aqueous<br />
solution <strong>of</strong> bleaching powder is added. A violet colour is thus produced<br />
(Eunge's reaction). This very sensitive reaction is given only<br />
by aqueous solutions oifree aniline and not by those <strong>of</strong> its salts, from<br />
which it must first be isolated.<br />
The reaction may also be used to detect small quantities <strong>of</strong><br />
benzene or <strong>of</strong> nitrobenzene, after these have been converted in the<br />
manner just described, by reactions carried out in a test tube.<br />
The bleaching powder reaction is peculiar to aniline; the dye<br />
which is formed is a complex quinone derivative the constitution <strong>of</strong><br />
which is not yet known with complete certainty. The other experiments,<br />
about to be described, are group reactions for primary aromatic<br />
amines.<br />
2. Primary and secondary amines are acylated by acid chlorides<br />
and anhydrides, in particular also by the chloride <strong>of</strong> benzene sulphonic<br />
acid (p. 192). The preparation <strong>of</strong> acetanilide has already been described<br />
(pp. 125, 128). The acetyl- and benzoyl-derivatives <strong>of</strong> all the<br />
simpler primary amines <strong>of</strong> the benzene and naphthalene series are known,<br />
so that these derivatives can always serve for purposes <strong>of</strong> identification.<br />
As an exercise a primary amine should be identified in the manner<br />
described.<br />
3. Benzylidene-aniline.—Aniline (1 c.c.) is heated in a test tube<br />
on the water bath with an equal quantity <strong>of</strong> benzaldehyde. The<br />
mixture becomes turbid because water separates. On cooling a<br />
solid is formed, a so-called SchifE's base (azomethine). Melting<br />
point 72°.<br />
This feebly basic condensation product is decomposed into its components<br />
when warmed with acid. The reaction is a general one for<br />
primary amines.<br />
4. Isonitrile Reaction.—Like the primary aliphatic amines <strong>of</strong> the<br />
methylamine type, aniline and its analogues give a characteristic odour<br />
with chlor<strong>of</strong>orm and alkali.<br />
Aniline (2 drops) and alcohol (2 c.c.) are mixed in a test tube<br />
and 0-5 c.c. <strong>of</strong> concentrated potassium hydroxide solution along with<br />
about five drops <strong>of</strong> chlor<strong>of</strong>orm are added. The mixture is then<br />
gently warmed in a fume chamber.<br />
n.<br />
C6H5.NH2 + C12C< +3K0H = C6H5.N:
168 ALKYLATION OF ANILINE<br />
In a quite analogous way ammonia yields hydrocyanic acid.<br />
H.NH2 + C12C< +3K0H = 2<br />
\H<br />
The question <strong>of</strong> the constitution <strong>of</strong> hydrocyanic acid has already been<br />
considered (p. 139). Here it need only be remarked that the isonitriles<br />
are converted by hydrolysis into primary amines and formic acid; no<br />
carbon monoxide is produced, although from the formula this might be<br />
expected. The reason for this is to be sought in the fact that the first<br />
stage in the reaction consists in the addition <strong>of</strong> water to the two free<br />
valencies <strong>of</strong> the carbon atom. The reaction must therefore be formulated<br />
thus :<br />
z .OH /OH<br />
C6H5.N:C< +H2O = C6H5.N:C< = C6H5.NH2 <<br />
\ \H<br />
tso-form <strong>of</strong> formanilide<br />
It is consequently no argument against the carbimine structure <strong>of</strong><br />
hydrocyanic acid that it likewise does not yield carbon monoxide<br />
but formic acid (in addition to ammonia) on decomposition by mineral<br />
acids.<br />
In a similar way fulminic acid, another derivative <strong>of</strong> bivalent carbon,<br />
which has been accurately investigated and for which the carboxime<br />
>C:NOH constitution has been established, is decomposed into formic<br />
acid and hydroxylamine (see experiment on p. 159).<br />
5. H<strong>of</strong>mann's method for the synthesis <strong>of</strong> alkylamines can be<br />
applied to the alkylation <strong>of</strong> aniline. The methylated anilines are<br />
especially important, and in particular the tertiary base dimeihylaniline,<br />
which will be repeatedly used in this practical course as starting material<br />
and is also much used technically. On a large scale aniline (in the form<br />
<strong>of</strong> its hydrochloride) is methylated in an autoclave with methyl alcohol.<br />
The methyl chloride which is thus produced is the actual alkylating<br />
agent. At very high temperatures the methyl group wanders from the<br />
nitrogen to the yara-position. This is a new example <strong>of</strong> the rearrangements<br />
which benzene derivatives undergo. Such rearrangements will<br />
be repeatedly mentioned (cf. p. 187).<br />
H Cl H Cl nxT<br />
\ /<br />
NH.CH,<br />
—><br />
CH3<br />
If the reaction takes place in the presence <strong>of</strong> an excess <strong>of</strong> methyl<br />
alcohol mesidine (formula on the right, above) is ultimately produced as
DIPHEJSTYLTHIOUKEA 169<br />
a result <strong>of</strong> further methylation and wandering (A. W. H<strong>of</strong>mann). This<br />
reaction does not proceed smoothly and has no preparative importance.<br />
6. Reaction with Carbon Bisulphide.—Ammonia and the primary<br />
amines <strong>of</strong> the aliphatic series combine with carbon bisulphide to form<br />
ammonium salts <strong>of</strong> dithiocarbamic acids, e.g.<br />
/SH HsN.CHa /SNHg.CHg<br />
/ HsN.CHa<br />
:S + H2N.CH3 —y S:C< — > S:C<br />
3 NH.CH3<br />
In the aromatic series, however, the reaction at once proceeds<br />
further. From the dithiocarbamate first formed, hydrogen sulphide is<br />
eliminated, and the phenyl isothiocyanate which remains combines, in<br />
its turn, with a second molecule <strong>of</strong> amine, giving a diarylthiourea.<br />
/SH.NH2C6H5<br />
S:C< >• S:C:N.C6H5 + H2S + H2N.C6H5<br />
\NH.C6H5<br />
Dithiocarbamate Phenylisothiocyanate (Mustard oil)<br />
CHNH /NH.C6H5<br />
c ' H - NH s, S:C<<br />
\NH.C6H5<br />
Diphenylthiourea<br />
In order to obtain an isothiocyanate in the aliphatic series, a dithiocarbamate<br />
must be distilled with a salt <strong>of</strong> a heavy metal (HgCl2, FeCl3)<br />
(A. W. H<strong>of</strong>mann). Here, in the case <strong>of</strong> diphenylthiourea, the distillation<br />
is carried out with concentrated hydrochloric acid.<br />
Diphenylthiourea (Thiocarbanilide).—In a round-bottomed flask<br />
provided with a long reflux condenser 20 g. <strong>of</strong> aniline, 25 g. <strong>of</strong> carbon<br />
bisulphide, 25 g. <strong>of</strong> alcohol, and 5 g. <strong>of</strong> finely powdered potassium<br />
hydroxide are kept gently boiling on the water bath for three hours.<br />
Carbon bisulphide and alcohol are then removed by distillation<br />
through a downward condenser and water is added to the residue.<br />
The crystalline material which has been produced is filtered with<br />
suction and washed successively with water, dilute hydrochloric<br />
acid, and again with water. After drying, the product weighs<br />
15-18 g. A small amount is recrystallised from alcohol (melting<br />
point 154°) and the rest is used without further purification for the<br />
preparation <strong>of</strong> phenylisothiocyanate. Of the crude product 15 g. are<br />
heated on the sand bath with 60 c.c. <strong>of</strong> concentrated hydrochloric<br />
acid (d. 1-18) in a 250 c.c. flask to which a downward condenser is<br />
attached. When, as a result <strong>of</strong> distillation, the volume <strong>of</strong> the material<br />
in the flask has been reduced to 10-15 c.c, the distillate is diluted<br />
with its own volume <strong>of</strong> water and extracted with ether. The
170 TEIPHBNYLGUANIDINB<br />
ethereal solution is shaken with a little sodium carbonate solution<br />
and dried with calcium chloride. The residue left after evaporation<br />
<strong>of</strong> the ether is distilled. Boiling point 222°. Yield almost quantitative.<br />
Besides isothiocyanate, there is produced by the action <strong>of</strong> hydrochloric<br />
acid on thiocarbanilide triphenylguanidine, which separates<br />
as hydrochloride when the residue in the flask is diluted with 50 c.c.<br />
<strong>of</strong> water and allowed to stand for several hours. The free base is<br />
obtained by decomposing the salt with warm sodium hydroxide<br />
solution. Triphenylguanidine crystallises from alcohol in colourless<br />
needles which melt at 143°.<br />
In the reaction described above the chief effect <strong>of</strong> the concentrated<br />
hydrochloric acid is to eliminate aniline :<br />
S:<br />
NH •C6H5<br />
S:C:N.CRH5 + H9N.CfiHs<br />
^|NH.C6H5| Phenyl mustard oil<br />
At the same time a small amount <strong>of</strong> hydrogen sulphide is also eliminated.<br />
The main product <strong>of</strong> this reaction, carbodiphenylimide (diphenylcyanamide),<br />
an extremely reactive substance, combines with the<br />
aniline present in the solution to form triphenylguanidine in the same<br />
way as, from cyanamide itself and ammonia, the unsubstituted guanidine<br />
is formed.<br />
S: C —• H5C6.N:C:N.C6H5 +<br />
HN.C6H5<br />
/NH.C6H6<br />
H5C6N:C/<br />
Triphenylguanidine<br />
The isothiocyanates undergo fundamentally the same addition<br />
reactions as the isologous cyanic esters (see p. 153), e.g. O:C:N.C6H5.<br />
They react, however, much more slowly. This follows already<br />
from the method <strong>of</strong> preparation <strong>of</strong> phenyl isothiocyanate (phenyl<br />
cyanate is at once decomposed by water).<br />
The addition <strong>of</strong> aniline to phenyl isothiocyanate which leads to<br />
the re-formation <strong>of</strong> diphenylthiourea is described in the succeeding<br />
paragraph.<br />
Phenyl isothiocyanate (5 drops) is mixed in a small test tube
MBTA-NITEANILINB 171<br />
with an equal amount <strong>of</strong> aniline and the mixture is gently heated in<br />
a small flame. The product solidifies to crystalline thiocarbanilide<br />
when rubbed with a glass rod. A small sample <strong>of</strong> the material<br />
may be purified by recrystallisation from alcohol for the purpose <strong>of</strong><br />
determining the melting point.<br />
When phenyl isothiocyanate is heated with, yellow mercuric oxide<br />
the sulphur is replaced by oxygen and the corresponding cyanate,<br />
which can be recognised by its exceptionally pungent odour, is obtained :<br />
C6H5.NCS + HgO = C6H5.NCO + HgS .<br />
Phenyl cyanate<br />
Experiment.—Phenyl isothiocyanate (0-5 c.c.) is heated for some<br />
time in a test tube with an equal volume <strong>of</strong> yellow mercuric oxide.<br />
Heating is continued until the isothiocyanate boils. The yellow<br />
oxide is converted into black mercuric sulphide and at the same time<br />
the extremely pungent odour <strong>of</strong> phenyl cyanate is observed ; its<br />
vapour has a powerful lachrymatory effect.<br />
(6) m-NlTEANILINE FROM m-DlNITROBENZENE<br />
The recrystallised dinitrobenzene is dissolved in hot alcohol (5 c.c.<br />
per gramme <strong>of</strong> dinitrobenzene) and the solution is rapidly cooled,<br />
which causes part <strong>of</strong> the dinitro-compound to separate again. Concentrated<br />
ammonia solution (d. 0-913 ; 0-8 g. per gramme <strong>of</strong> dinitrobenzene)<br />
is now added, the flask and contents are weighed, and the<br />
solution is saturated with hydrogen sulphide at the ordinary temperature.<br />
Then the current <strong>of</strong> hydrogen sulphide is shut <strong>of</strong>f and<br />
the flask is heated for half an hour under reflux condenser on the<br />
water bath. Passing in <strong>of</strong> hydrogen sulphide in the cold and subsequent<br />
heating are repeated until, for each gramme <strong>of</strong> dinitrobenzene<br />
taken, an increase in weight <strong>of</strong> 0-6 g. has occurred. If, as a result <strong>of</strong><br />
insufficient cooling, the necessary increase in weight is not attained,<br />
the shortage is neglected and hydrogen sulphide is passed in three<br />
times altogether. The product is diluted with water and filtered.<br />
The precipitate which has been separated is washed with water and<br />
repeatedly extracted with warm dilute hydrochloric acid. Finally,<br />
the nitraniline in the acid filtrates is liberated by neutralisation with<br />
ammonia and is recrystallised from water. Melting point 114°.<br />
Yield 70-80 per cent <strong>of</strong> the theoretical.
172 MBTA-PHBNYLBNBDIAMINB<br />
If it is desired to avoid working with hydrogen sulphide, commercial<br />
sodium sulphide may be used as reducing agent. 1<br />
The complete reduction <strong>of</strong> nitro-compounds which contain several<br />
nitro-groups is carried out in the same way as in the case <strong>of</strong> mononitroderivatives.<br />
If, however, only partial reduction is desired, the use <strong>of</strong><br />
ammonium hydrosulphide is advantageous.<br />
/NO2<br />
NO2<br />
C6H4< + 3 NH4SH = C6H,< + 2 H2O + 3 S + 3 NH3 .<br />
X<br />
NO \NH<br />
For the reduction <strong>of</strong> nitro-compounds containing a group which<br />
may be attacked by nascent hydrogen, as, for example, an aldehyde<br />
group, an unsaturated side chain, and so on, special methods must be<br />
applied. In such cases ferrous hydroxide or iron powder (cf. Chap. VII.<br />
5, arsanilic acid) are <strong>of</strong>ten used. The reduction is carried out thus : a<br />
weighed amount <strong>of</strong> ferrous sulphate is caused to act, in the presence <strong>of</strong><br />
alkali (potassium or sodium hydroxide, baryta), on the substance to be<br />
reduced. In this way it is possible to reduce, for example, o-nitrobenzaldehyde<br />
to aminobenzaldehyde, and o-nitrocinnamic acid to aminocinnamic<br />
acid.<br />
The yield <strong>of</strong> m-nitraniline when prepared as described above is only<br />
about four-fifths <strong>of</strong> the theoretically possible amount. This indicates,<br />
quite clearly, that the intermediate reduction products are reduced<br />
further much more rapidly than is an intact nitro-group.<br />
When m-dinitrobenzene is reduced in an acid medium the product<br />
is m-j>henylenediamine :<br />
NH,<br />
-NH,<br />
a di-acid base <strong>of</strong> technical importance. On diazotisation it yields the<br />
brown dye vesuvine or Bismarck brown. Hence m-phenylenediamine<br />
is used to test for traces <strong>of</strong> nitrites in water supplies.<br />
o- and y-Nitranilines are prepared by nitration <strong>of</strong> aniline. Since<br />
aniline is very sensitive towards oxidising agents, the amino-group must<br />
be protected. This is most simply secured by acetylation. Acetanilide<br />
is nitrated and, according to the conditions chosen, a large yield <strong>of</strong> either<br />
the o- or the y-compound can be produced. The acetyl-group is subsequently<br />
removed by hydrolysis. y-Nitraniline is also obtained in a<br />
simpler way. y-Nitrochlorobenzene (which can be prepared by nitration<br />
<strong>of</strong> chlorobenzene) is caused to react with ammonia at a high temperature<br />
and under high pressure.<br />
1 For details see Cobenzl, Chem.-Ztg., 1913, 37, 299; see also Ullmann, Enzyhlopadie,<br />
2nd edition, vol. i. p. 470.
BASICITY OF THE NITEANILINBS 173<br />
On the mobilising effect <strong>of</strong> nitro-groups on halogens, cf. p. 106.<br />
The basic character <strong>of</strong> the amino-group in aniline, which is in itself<br />
feeble, is already greatly reduced by the entrance <strong>of</strong> a single nitro-group.<br />
Hence the three nitranilines are very weak bases which dissolve only in<br />
excess <strong>of</strong> acid to form salts. Whilst the nitranilines themselves are <strong>of</strong> a<br />
deep orange-yellow colour, their salts, when pure, are colourless. The<br />
powerful colour-deepening (bathochromic) influence which the free<br />
amino-group exerts on nitrobenzene (itself almost colourless when perfectly<br />
pure) is completely abolished by salt formation, i.e. by conversion<br />
<strong>of</strong> the unsaturated trivalent nitrogen into that <strong>of</strong> an ammonium compound.<br />
Of the three nitranilines the o-compound is the most feebly basic,<br />
then comes the p- and finally the m-compound.<br />
These facts illustrate relationships which are <strong>of</strong> great importance<br />
throughout the whole chemistry <strong>of</strong> aromatic compounds, and have<br />
already been mentioned above in connexion with the mobilisation <strong>of</strong><br />
halogens by nitro-groups in the o- and y-positions. Altogether two<br />
substituents in ortho- or in para-positions have a much stronger influence<br />
on each other than is exerted mutually by two substituents which are<br />
meta to each other. A satisfactory explanation <strong>of</strong> these facts has not<br />
yet been found although the close relationships between the 1 and 2 and<br />
the 1 and 4 positions (Thiele) throw some light on the question.<br />
B<br />
The unequal basicities <strong>of</strong> the three nitranilines can be illustrated by<br />
the following experiment. It is a general property <strong>of</strong> the salts <strong>of</strong> weak<br />
bases—as well as <strong>of</strong> weak acids—that in aqueous solution they are stable<br />
only if an excess <strong>of</strong> acid (or alkali) is present. When such solutions are<br />
diluted with water hydrolysis occurs as a result <strong>of</strong> the operation <strong>of</strong> the<br />
law <strong>of</strong> mass action. In the present case this phenomenon shows itself<br />
in the appearance <strong>of</strong> the yellow colour characteristic <strong>of</strong> the bases and<br />
finally, since the nitranilines are sparingly soluble in water, in their precipitation<br />
in crystalline form. The weaker the base the smaller is the<br />
amount <strong>of</strong> water which must be added in order to make the hydrolysis<br />
perceptible.<br />
Experiment.—Of each <strong>of</strong> the three nitranilines—they can be<br />
procured in any laboratory—0-5 g. is separately dissolved by stirring<br />
with glass rods in three test tubes, each containing 3 c.c. <strong>of</strong> concentrated<br />
sulphuric acid. The colourless solutions thus prepared
174 PHENYLHYDKOXYLAMINE<br />
are then poured, separately, into beakers each containing 200 c.c.<br />
<strong>of</strong> water. o-Nitraniline is partially precipitated from the yellow<br />
solution produced, the somewhat more basic ^-compound remains in<br />
solution but is yellow in colour, whilst the solution <strong>of</strong> m-nitraniline<br />
sulphate remains colourless.<br />
4. PHENYLHYDROXYLAMINE 1<br />
A solution <strong>of</strong> 20 g. <strong>of</strong> ammonium chloride in 400 c.c. <strong>of</strong> water is<br />
mixed in a thick-walled filter jar (capacity about 2 1.) with 40 g. <strong>of</strong><br />
freshly distilled nitrobenzene. To this mixture, which is continuously<br />
and vigorously stirred (preferably with a wooden rod with wide end),<br />
60 g. <strong>of</strong> zinc dust (purity at least 75 per cent) are added during the<br />
course <strong>of</strong> forty minutes. The temperature is maintained at or below<br />
10° by throwing in small pieces <strong>of</strong> ice.<br />
After all the zinc has been added, stirring is continued for ten<br />
minutes—the odour <strong>of</strong> the nitrobenzene should then have disappeared—and<br />
the zinc hydroxide is at once removed by filtration<br />
with suction on a Biichner funnel. The nitrate (solution I) is poured<br />
into a beaker. The sludge <strong>of</strong> zinc hydroxide is washed on the funnel<br />
with 400 c.c. <strong>of</strong> water at 45° in the following manner : the funnel is<br />
filled with water which is then carefully mixed with the hydroxide<br />
by stirring, while as yet no suction is applied ; then, by gentle<br />
suction, the solution is slowly filtered, and finally, with the pump full<br />
on, the residue in the funnel is pressed with a glass stopper (solution<br />
II). In each <strong>of</strong> the two aqueous solutions 120 g. <strong>of</strong> finely<br />
powdered sodium chloride are completely dissolved, which precipitates<br />
the phenylhydroxylamine in fine crystalline flocks. The<br />
suspension is allowed to stand in ice for half an hour and is then<br />
filtered at the pump as dry as possible. The phenylhydroxylamine<br />
is pressed on porous plate and can be recrystallised from a little<br />
benzene to which petrol ether is added. In this way the substance<br />
is obtained in the form <strong>of</strong> s<strong>of</strong>t felted glistening needles which are<br />
quite pure and can be preserved for some time. Melting point 81°.<br />
For further work no special purification is necessary, however.<br />
Yield <strong>of</strong> dry material 75-80 per cent <strong>of</strong> the theoretical.<br />
The material from solution I is usually purer than that from the<br />
other filtrate, but otherwise there is no reason why the two solutions<br />
1 E. Bamberger, Ber., 1890, 27, 1347; A. Wohl, Ber., 1890, 27, 1432.
A K Y L H Y D K O X Y L A M I N E S 1 7 5<br />
s h o u l d n o t b e c o m b i n e d . P h e n y l h y d r o x y l a m i n e , w h i c h h a s n o t b e e n<br />
r e c r y s t a l l i s e d , c a n o n l y b e p r e s e r v e d u n d e c o m p o s e d f o r a f e w d a y s a t<br />
t h e m o s t .<br />
C a r e s h o u l d b e t a k e n n o t t o a l l o w p h e n y l h y d r o x y l a m i n e , e s p e c i a l l y<br />
w h e n i n s o l u t i o n , t o c o m e i n t o c o n t a c t w i t h t h e s k i n . I n m a n y i n d i -<br />
v i d u a l s i t p r o d u c e s s e v e r e e c z e m a , w h i l s t o t h e r s a r e q u i t e u n a f f e c t e d .<br />
A m m o n i u m h y d r o g e n s u l p h i d e is a l s o a v e r y s u i t a b l e r e a g e n t f o r<br />
t h e r e d u c t i o n <strong>of</strong> n i t r o c o m p o u n d s t o a r y l h y d r o x y l a m i n e s ; i t is u s e d i n<br />
a l c o h o l i c s o l u t i o n i n t h e c o l d . 1<br />
A n a l u m i n i u m - m e r c u r y c o u p l e a c t s i n t h e s a m e w a y a s z i n c d u s t .<br />
T h i s a l u m i n i u m a m a l g a m , p r e p a r e d b y t h e a c t i o n <strong>of</strong> m e r c u r i c c h l o r i d e<br />
o n a l u m i n i u m ( p r e f e r a b l y g r a n u l a t e d ) , is a l s o s u i t a b l e f o r r e d u c i n g s u b -<br />
s t a n c e s d i s s o l v e d i n e t h e r o r a l c o h o l ; t h e w a t e r w h i c h is r e q u i r e d is<br />
s l o w l y a d d e d d r o p b y d r o p . ( T h e m e t h o d is t h a t <strong>of</strong> H . W i s l i c e n u s . )<br />
T h e e x t e n t <strong>of</strong> t h e r e d u c t i o n v a r i e s a c c o r d i n g t o t h e n i t r o - c o m p o u n d c o n -<br />
c e r n e d , b u t c o r r e s p o n d s a p p r o x i m a t e l y t o t h e e f f e c t <strong>of</strong> z i n c d u s t i n a<br />
n e u t r a l m e d i u m . C o n s e q u e n t l y r e d u c t i o n u s u a l l y d o e s n o t p r o c e e d<br />
b e y o n d t h e h y d r o x y l a m i n e s t a g e .<br />
P h e n y l h y d r o x y l a m i n e , e s p e c i a l l y w h e n i m p u r e , is v e r y u n s t a b l e . I t<br />
d a r k e n s a n d d e c o m p o s e s e v e n i n a c l o s e d c o n t a i n e r w h e n k e p t f o r a<br />
s h o r t t i m e . T h e p u r e m a t e r i a l c a n b e k e p t f o r a c o n s i d e r a b l e t i m e i n<br />
a d e s i c c a t o r .<br />
I n c o n t r a s t t o t h e p a r e n t s u b s t a n c e <strong>of</strong> t h e s e r i e s , y - t o l y l h y d r o x y l<br />
a m i n e , w h i c h is p r e p a r e d b y t h e r e d u c t i o n w i t h z i n c d u s t <strong>of</strong> y - n i t r o -<br />
t o l u e n e i n b o i l i n g a l c o h o l , is a q u i t e s t a b l e c o m p o u n d .<br />
T h e a r y l h y d r o x y l a m i n e s a r e w e a k b a s e s w h i c h d i s s o l v e i n d i l u t e a c i d s<br />
t o f o r m s a l t s . T h e i n s t a b i l i t y <strong>of</strong> p h e n y l h y d r o x y l a m i n e h a s t h r e e c a u s e s :<br />
t h e e f f e c t <strong>of</strong> a t m o s p h e r i c o x y g e n , <strong>of</strong> a l k a l i s , a n d <strong>of</strong> a c i d s . O n e x p o s u r e<br />
t o a i r t h e c o m p o u n d , e s p e c i a l l y if i m p u r e , is o x i d i s e d t o n i t r o s o b e n z e n e ,<br />
w h i c h c a n b e d e t e c t e d i n d e c o m p o s i n g p h e n y l h y d r o x y l a m i n e b y i t s<br />
p u n g e n t o d o u r . A s is o f t e n t h e c a s e , t h e v e l o c i t y <strong>of</strong> t h i s p r o c e s s , w h i c h<br />
is k n o w n a s a u t o x i d a t i o n , is i n c r e a s e d b y a l k a l i s ; it is a c c o m p a n i e d b y<br />
t h e p r o d u c t i o n <strong>of</strong> h y d r o g e n p e r o x i d e a c c o r d i n g t o t h e e q u a t i o n :<br />
C 6 H 5 . N H O H + O 2 — > C 6 H 5 . N O + H 2 O 2<br />
Since nitrosobenzene condenses with phenylhydroxylamine forming<br />
azoxybenzene, the latter substance occurs amongst the decomposition<br />
products <strong>of</strong> phenylhydroxylamine. Also, by the action <strong>of</strong> alkalis, water<br />
is eliminated and azobenzene is produced. The action <strong>of</strong> acids will be<br />
discussed below.<br />
ATT<br />
L i k e h y d r o x y l a m i n e itself, all its d e r i v a t i v e s <strong>of</strong> t h e f o r m R . N < T T<br />
a r e r e d u c i n g a g e n t s .<br />
1 Willstfttter, Ber., 1908, 4 1 , 1936.
176 CHANGE TO AMINOPHENOLS<br />
Experiment.—Test the reducing effect <strong>of</strong> phenylhydroxylamine<br />
by dissolving material on the point <strong>of</strong> a knife in 2 c.c. <strong>of</strong> warm water<br />
and adding to the solution a few drops <strong>of</strong> ammoniacal silver nitrate<br />
solution.<br />
Experiment. — Isomeric change <strong>of</strong> phenylhydroxylamine to paminophenol.<br />
1 The base (2-2 g.; 0-02 mole) is added in small<br />
portions to a mixture <strong>of</strong> 10 c.c. <strong>of</strong> concentrated sulphuric acid and<br />
30 g. <strong>of</strong> ice, externally cooled by more ice.<br />
The solution is diluted with 200 c.c. <strong>of</strong> water and boiled until a<br />
sample, when mixed with dichromate solution, no longer smells <strong>of</strong><br />
nitrosobenzene but <strong>of</strong> quinone (ten to fifteen minutes). To the<br />
cooled solution 2 g. <strong>of</strong> dichromate dissolved in water are added, a<br />
downward condenser is attached to the flask containing the mixture,<br />
and steam is passed through. The quinone is carried over with the<br />
steam. On the mechanism <strong>of</strong> its formation in this reaction compare<br />
p. 310. Test the residue in the flask for ammonia.<br />
The change which arylhydroxylamines undergo by the action <strong>of</strong><br />
mineral acids, especially when warm, is worthy <strong>of</strong> special note. If the<br />
position para to the NHOH-group is free, a rearrangement takes place<br />
to the isomeric p-aminophenol, e.g. in the case <strong>of</strong> phenylhydroxylamine<br />
according to the equation :<br />
H OH<br />
HOH NH2<br />
A process for the direct reduction <strong>of</strong> nitrobenzene to ji-aminophenol,<br />
an important intermediate for the production <strong>of</strong> dyes, depends on the<br />
above interesting transformation. Nitrobenzene in alcoholic solution<br />
is mixed with concentrated sulphuric acid and electrolysed with a lead<br />
cathode. This process proves that phenylhydroxylamine is also an<br />
intermediate in the reduction <strong>of</strong> nitrobenzene in acid solution, as was<br />
mentioned above. Here, as a result <strong>of</strong> the rapidity <strong>of</strong> the rearrangement<br />
which takes place, it is not converted into aniline.<br />
In the experiment described above, the y-aminophenol is not isolated<br />
but converted by oxidation into quinone.<br />
If the position para to the NHOH-group is occupied, as, for example,<br />
in y-tolylhydroxylamine, the catalytic action <strong>of</strong> strong acids produces<br />
a different result. The hydroxyl group is indeed shifted to the carbon<br />
atom in the y-position, but this leads to the production <strong>of</strong> a quinonelike<br />
substance :<br />
1 Bamberger, Ber., 1890, 27, 1552.<br />
I
NITKOSOHYDKOXYLAMINES 177<br />
CH3 CH3 HO<br />
IOH NH<br />
This " quinolimine " contains the quinonoid imino-group, which is<br />
very unstable towards acids and is eliminated hydrolytically in the form<br />
<strong>of</strong> ammonia, being replaced by oxygen :<br />
CH, OH CH, OH<br />
NH 0<br />
There is thus formed as final product <strong>of</strong> the rearrangement the<br />
simplest <strong>of</strong> the quinols, a substance which is very soluble in water, is<br />
colourless, in contrast to quinone, and is difficult to prepare (Bamberger).<br />
Experiment. — Nitrosophenylhydroxylamine. 1 Phenylhydroxylamine<br />
(2-2 g.) is dissolved in 20 c.c. <strong>of</strong> 2V-hydrochloric acid and an<br />
aqueous solution <strong>of</strong> 1 -4 g. <strong>of</strong> sodium nitrite is rather quickly added<br />
with strong cooling in ice. White needles are at once precipitated.<br />
They are filtered with suction, washed with ice-cold water, and dried<br />
on porous plate. Melting point 59°.<br />
The substance is dissolved in ether and by passing in dry ammonia<br />
gas the ammonium salt is precipitated. From this salt the<br />
iron and copper salts, insoluble in water, are prepared by precipitation<br />
with Fe + + + and Cu++ (" Cupferron ").<br />
In this reaction phenylhydroxylamine behaves like a secondary<br />
amine. To the class <strong>of</strong> nitrosohydroxylamines there belong also the<br />
so-called isonitramines and the compound <strong>of</strong> nitric oxide and potassium<br />
sulphite.<br />
KO3S—N—OK<br />
The formation <strong>of</strong> the ammonium salt and the analytical application <strong>of</strong><br />
nitrosophenylhydroxylamine as a reagent for the determination <strong>of</strong> iron<br />
and copper show that compounds <strong>of</strong> this kind are acidic.<br />
Phenylhydroxylamine condenses with aldehydes, e.g. benzalde-<br />
1 Bamberger, Bar.. 1890, 27, 1552.<br />
NO
178 NITKOSOHYDKOXYLAMINES<br />
hyde, in the same way as it does with, nitrosobenzene (cf. the following<br />
section, 5) :<br />
C6H5.N. H H<br />
C6H5.N—C.C6H5<br />
OH ' 01 !)H<br />
C6H5.N=CH.C6H5<br />
-H,0<br />
— > 6<br />
Substances <strong>of</strong> this kind are called " nitrones ". Their method <strong>of</strong><br />
formation is quite analogous to that <strong>of</strong> the oximes from aldehydes and<br />
hydroxylamine.<br />
These nitrones are identical with the N-ethers <strong>of</strong> the aldoximes and<br />
are also formed—when an alkyl group occupies the place <strong>of</strong> C6H5—by<br />
the action <strong>of</strong> alkyl halides on the stereoisomeric /2-aldoximes :<br />
R.CH R.CH<br />
|| +CH3Br —>• || +HBr.<br />
HON ON—CH3<br />
The nitrone from phenylhydroxylamine and benzaldehyde can<br />
easily be prepared in beautiful crystals from alcoholic solutions <strong>of</strong><br />
these components.<br />
Finally, it is interesting to note that the reduction <strong>of</strong> nitroelhylene,<br />
an olefinic nitro-compound having a structure analogous to that <strong>of</strong><br />
nitrobenzene, leads to acetaldoxime.<br />
H2C:CH.NO2 + 4H = H3C.C:NOH + H2O .<br />
H<br />
Phenylnitroethylene, which is much more easily obtained (see p.<br />
160), reacts in an analogous manner, yielding phenylacetaldoxime<br />
C6H5.CH2.C=NOH (Bouveault). In any case both these nitroethy-<br />
H<br />
lenes first yield derivatives corresponding to phenylhydroxylamine.<br />
These derivatives, however, undergo immediate rearrangement to the<br />
stable oxime form :<br />
R.CH=C.NHOH —>• R.CH2.C=NOH.<br />
H H<br />
Such a rearrangement does not take place in the benzene ring,<br />
where the three neighbouring double linkages provide the most complete<br />
expression <strong>of</strong> saturation. Here the NHOH-group remains excluded<br />
from the ring, and the " aromatic " constitution <strong>of</strong> the nucleus<br />
is preserved.<br />
Similar considerations explain why, so far, it has been impossible to<br />
obtain an " aliphatic aniline " <strong>of</strong> the type R.CH:C
NITKOSOBENZENE 179<br />
5. NITROSOBENZENE<br />
Freshly prepared phenylhydroxylamine (12 g.) is dissolved as<br />
rapidly as possible by gradual addition to an ice-cold mixture <strong>of</strong><br />
50 c.c. <strong>of</strong> concentrated sulphuric acid and 250 c.c. <strong>of</strong> water. Icewater<br />
(500 c.c.) is now added to the solution, which is cooled to 0°,<br />
and then a likewise cold solution <strong>of</strong> 12 g. <strong>of</strong> sodium dichromate in<br />
200 c.c. <strong>of</strong> water is run in rather quickly from a dropping funnel,<br />
while the reaction flask is further cooled and shaken. The nitrosobenzene<br />
soon separates in yellow crystalline flocks. These are<br />
filtered with suction on a small Biichner funnel, washed twice with<br />
water, and transferred with the filter paper to a round-bottomed<br />
flask from which the easily volatile nitrosobenzene is distilled with<br />
steam. The green vapour which passes over deposits an almost<br />
colourless crystalline crust already in the condenser. Towards the<br />
end <strong>of</strong> the distillation the current <strong>of</strong> water through the latter is shut<br />
<strong>of</strong>f and the nitrosobenzene which has been deposited is cautiously<br />
melted with steam and run into the receiver. By nitration <strong>of</strong> the<br />
distillate the nitrosobenzene is separated, pressed on porous plate,<br />
and dried in a vacuum desiccator over calcium chloride (not over<br />
sulphuric acid). A sample <strong>of</strong> the dried material is washed in a test<br />
tube with a little ether (the solution is green) and again dried. This<br />
sample is used for determination <strong>of</strong> the melting point. Nitrosobenzene<br />
melts to a green liquid at 68°.<br />
It can be obtained in an absolutely pure, stable condition by<br />
recrystallisation from twice its weight <strong>of</strong> alcohol.<br />
Aromatic nitroso-compounds can also be obtained by oxidation <strong>of</strong><br />
primary amines, but only one oxidising agent is known with which, the<br />
process can satisfactorily be carried out. This reagent is monopersulphuric<br />
acid (Caro's acid) :<br />
C6H5.NH2 + 2 O —> C6H5.NO + H2O .<br />
Experiment. 1 —Powdered potassium persulphate (18 g.) is<br />
thoroughly ground in a mortar, well cooled in ice, with 15 c.c. <strong>of</strong><br />
concentrated sulphuric acid. The mixture, after standing for one<br />
hour, is poured on to 100 g. <strong>of</strong> ice and while being cooled is neutralised<br />
with crystalline sodium carbonate. Into this neutral solution<br />
100 c.c. <strong>of</strong> aniline water (2-8 g. <strong>of</strong> aniline in 100 c.c. <strong>of</strong> water) are<br />
poured. After a short time nitrosobenzene separates in yellow<br />
1 Caro, Z. anqew. Chem., 1898, 11, 845; Baeyer, Ber., 1900, 33, 124; Ber.,<br />
1901, 34, 855.
180 NITKOSOBENZENE<br />
flocks. The mixture is stirred and then, after the solid material has<br />
settled and the supernatant liquid is clear, filtered with suction. The<br />
nitrosobenzene is distilled with steam. The yield is equivalent to<br />
rather more than half the aniline taken.<br />
Apart from rare exceptions, the only nitroso-compounds known are<br />
those in which the NO-group is united to a tertiary carbon atom, as in<br />
nitrosobenzene. Nitrosoisobutane (H3C)3: C.NO, for example, is a representative<br />
from the aliphatic series.<br />
In the solid state almost all nitroso-compounds are colourless, 1 but<br />
when fused or in solution they are blue or green. Determinations <strong>of</strong><br />
the molecular weight <strong>of</strong> nitrosobenzene in liquid hydrogen cyanide have<br />
shown (Piloty) that the colourless form is bimolecular. The NO-groups<br />
<strong>of</strong> two molecules are loosely united in one <strong>of</strong> the ways indicated by the<br />
following formulae :<br />
C6HS.N=O C6HS.N—0<br />
[[ or I I -<br />
C6H5.N=O O-N.C6H5<br />
When the crystal structure is destroyed by fusion or dissolution, a<br />
dissociation into single coloured molecules occurs to an extent which<br />
increases with the temperature. This behaviour is exactly similar to<br />
that so well known in the case <strong>of</strong> nitrogen peroxide :<br />
(C6H5.NO)2 - T> 2 C6H5.NO ; (NO2)2 --^ 2 NO2.<br />
The NO-group is the most active colour-producing (chromophoric)<br />
group known. With a radical such as isobutyl which is <strong>of</strong> no account<br />
for the absorption <strong>of</strong> light, it produces a blue nitrosohydrocarbon. In<br />
spite <strong>of</strong> their intense coloration the nitroso-compounds are not dyes,<br />
since they lack the " auxochromic " groups (e.g. NH2 or OH) necessary<br />
for combination with textile fibres.<br />
In many respects the nitroso-group resembles the aldehyde group,<br />
i.e. the reactions which, in the aldehydes, are due to the reactivity <strong>of</strong><br />
the >C=O double bond can, for the most part, be reproduced with the<br />
nitroso-compounds in virtue <strong>of</strong> the reactivity <strong>of</strong> the —N=O double<br />
bond.<br />
The condensation <strong>of</strong> nitrosobenzene with phenylhydroxylamine<br />
which is described below is an example <strong>of</strong> this similarity. Hydroxylamine<br />
and phenylhydrazine also react with nitrosobenzene, but the<br />
details <strong>of</strong> these reactions cannot be given here.<br />
y-Nitrosodimethylamline, ON—
CONDENSATION OF NITEOSO-COMPOUNDS 181<br />
Aldehydes react with, primary amines to give the so-called azomethines<br />
(Schiff's bases), by elimination <strong>of</strong> water (p. 167), e.g.<br />
C6H5.C:O + H2N.C6H5 —> C6H5.C:N.C6H5 + H2O .<br />
H H<br />
Benzylideneaniline<br />
Similarly, nitrosobenzene and aniline give azobenzene :<br />
C6H5.NO + H2N.C6H5 —• C6H5.N:N.C6H5 + H2O.<br />
Experiment. 1 —Nitrosobenzene (1 g. in 10 c.c. <strong>of</strong> alcohol) is added<br />
to a solution <strong>of</strong> 1 c.c. <strong>of</strong> aniline in 3 c.c. <strong>of</strong> glacial acetic acid. On<br />
gentle warming the colour changes to dark orange. After heating<br />
for ten minutes longer on the boiling water bath, a few cubic centimetres<br />
<strong>of</strong> water are added. On cooling the solution azobenzene<br />
crystallises in orange-red platelets. Washed on the filter with 50<br />
per cent alcohol and dried on porous plate, it melts at 68°. Azobenzene<br />
can very readily be recrystallised from little alcohol.<br />
In this way mixed (asymmetrical) azo-compounds can conveniently<br />
be prepared in good yield. Prepare ji-methylazobenzene, for example,<br />
from nitrosobenzene and y-toluidine according to the precedure given<br />
above.<br />
Aldehydes condense with compounds containing a reactive methylor<br />
methylene-group to form unsaturated ketones, e.g.<br />
C6H5.C:O + H3C.CO.CH3 —> C6H5.C:CH.CO.CH3 .<br />
H H<br />
Benzylideneacetone<br />
An analogous reaction is known with aromatic nitroso-compounds, but<br />
for it an exceptionally mobile hydrogen atom must be present in the<br />
ketone and hence no condensation occurs with simple ketones such<br />
Us acetone. The products <strong>of</strong> the reaction are, <strong>of</strong> course, azomethines.<br />
This condensation has made possible the synthesis <strong>of</strong> 1 : 2 : 3-triketones<br />
(F. Sachs), e.g.<br />
CH3.CO.CH2.CO.CH3<br />
Acetylacetone<br />
CH3.CO<br />
I ,—,<br />
.N(CH3)2 + H2O<br />
CH3.CO.CO.CO.CH3 + H2N./ \N(CH3)2 .<br />
Triketopentane —<br />
1 A. Baeyer, Ber., 1874, 7, 1638.
182 AZOXYBENZENE<br />
The last phase <strong>of</strong> the reaction depends on the fact that azomethines<br />
are easily decomposed by acids into carbonyl compounds and primary<br />
base.<br />
The practical effect <strong>of</strong> the condensation consists, therefore, in the<br />
conversion <strong>of</strong> methylene into >C=O. The same result is attained in a<br />
quite similar reaction by the action <strong>of</strong> nitrous acid on ketones (cf. the<br />
synthesis <strong>of</strong> diacetyl from methylethyl ketone).<br />
Finally, nitrosobenzene reacts with Grignard reagents. With phenylmagnesium<br />
bromide, in the usual way there is produced diphenylhydroxylamine,<br />
an exceptionally reactive substance :<br />
C6H5.N:O + Br.Mg.C6H5.<br />
C6H5.N.C6H5 + MgBr(OH).<br />
OH<br />
Diphenylhydroxylamine, like phenylhydroxylamine, can best be dehydrogenated<br />
with silver oxide. Here only one H-atom, that from<br />
the OH-group, can be removed and the red crystalline substance which<br />
is thus produced contains quadrivalent nitrogen. Like nitrogen peroxide,<br />
therefore, this dehydrogenation product reacts like a free radicle. As<br />
its formula indicates, it is derived from nitrogen peroxide by the substitution<br />
<strong>of</strong> two C6H5-groups for one 0.<br />
H5C6s<br />
^N=0 Diphenylnitrogen oxide.<br />
HC/<br />
Experiment.—Azoxybenzenefrom phenylhydroxylamine and nitrosobenzene.—Phenylhydroxylamine<br />
(1 g.) is added to a solution <strong>of</strong> 1 g.<br />
<strong>of</strong> nitrosobenzene in 10 c.c. <strong>of</strong> alcohol. The mixture is shaken<br />
while a few drops <strong>of</strong> concentrated potassium hydroxide solution<br />
(1 : 1) are added, and is then wanned on the water bath for a few<br />
minutes. The yellowish-red solution thus formed deposits yellow<br />
crystals <strong>of</strong> the reaction-product when cooled and rubbed with a<br />
glass rod. Since azoxybenzene melts at 36°, it has a great tendency<br />
to separate from a supersaturated solution in the form <strong>of</strong> an oil.<br />
By recrystallisation from a little alcohol or from petrol ether (retain<br />
a few crystals for inoculation) the compound is obtained as a pale<br />
yellow or almost colourless solid.<br />
The feeble colour <strong>of</strong> azoxybenzene, in contrast to the red <strong>of</strong> azobenzene,<br />
would appear to be more readily intelligible on the basis <strong>of</strong> the<br />
old formula, I, than on that by which Angeli has replaced it, II:
HYDKAZOBENZENE 183<br />
I H5C6.N-N.C6H5, II C6H5.N=N.C6H5.<br />
Y H<br />
isomeric<br />
Nevertheless,<br />
forms (Angeli),<br />
the existence <strong>of</strong> asymmetrical azoxybenzenes in two<br />
R.N=N.R' and R.N=N.R'<br />
4 &<br />
convincingly<br />
The mechanism<br />
supports<br />
<strong>of</strong><br />
formula<br />
the condensation<br />
II.<br />
sponds entirely to the production <strong>of</strong> nitrones<br />
described<br />
from phenylhydroxylamine<br />
is plain, and core-<br />
and aldehydes (p. 178):<br />
C6HS.NH + ON.C6H6 C6H5.N—N.C6H6 ,_HQ C8H5.N:N.C6H5<br />
OH OH OH > 0<br />
discused<br />
The relationships<br />
in the explanations<br />
<strong>of</strong> azoxybenzene<br />
given for<br />
to<br />
the<br />
azonext<br />
and<br />
preparation.<br />
hydrazobenzene are<br />
result<br />
The<br />
<strong>of</strong><br />
interesting<br />
the action<br />
rearangement<br />
<strong>of</strong> concentrated<br />
which<br />
sulphuric<br />
azoxybenzene<br />
acid may<br />
undergoes<br />
also be mention<br />
as a<br />
here,<br />
is formed<br />
p- Hydroxyazobenzene,<br />
by this rearangement (Walach).<br />
the parent substance o<br />
C6H5.N=N.C6H5 —>• C6H5.N=N—/~\—OH.<br />
0<br />
6. HYDRAZOBENZENE AND AZOBENZENE<br />
(a) HYDRAZOBENZENE<br />
A round-bottomed flask (capacity 1 1.) is provided with a wellfitting<br />
thin-walled double neck attachment (Fig. 30). An ascending<br />
Liebig condenser is clamped obliquely and its inner tube is joined<br />
by a short wide rubber tube to the oblique neck in such a way that<br />
the flask can be vigorously shaken without trouble. The upright<br />
neck, which serves for the introduction <strong>of</strong> the zinc dust required for<br />
the reduction, is closed with a cork.<br />
Sodium hydroxide (50 g.) is dissolved in 150 c.c. <strong>of</strong> water, and the<br />
solution, while still warm, is poured into the flask, along with 50 c.c.<br />
<strong>of</strong> alcohol and 41 g. (0-33 mole) <strong>of</strong> nitrobenzene. Zinc dust (6-8 g.) is<br />
now added with vigorous shaking which is continued until the<br />
reaction, at first rather violent, has ceased. The reaction mixture
184 HYDKAZOBENZENE AND AZOBENZENE<br />
is then kept boiling by continuous addition <strong>of</strong> zinc dust. The reaction<br />
should not be allowed to become too violent, but, on the other<br />
hand, it should not be interrupted by cooling.<br />
The contents <strong>of</strong> the flask become at first red (azobenzene), but<br />
finally turn pale yellow when the necessary amount <strong>of</strong> reducing<br />
agent has had its effect. About 120 to 150 g. <strong>of</strong> 75 per cent zinc dust<br />
are required. If the reaction should cease prematurely, the flask<br />
is heated on a vigorously boiling water bath.<br />
It is essential that the contents <strong>of</strong> the flask be continually<br />
agitated by vigorous shaking in order that the heavy dust may<br />
remain in contact with the organic substance.<br />
When the reduction is complete, the mixture is heated on the<br />
water bath and 500 c.c. <strong>of</strong> alcohol are added. The precipitated<br />
hydrazobenzene dissolves in this alcohol at the boiling point. The<br />
whole contents <strong>of</strong> the flask are filtered while boiling hot through a<br />
Biichner funnel [flames in the vicinity must first be extinguished), the<br />
flask is at once washed out with 50 c.c. <strong>of</strong> hot alcohol, and this<br />
alcohol is used to wash the excess <strong>of</strong> zinc dust on the funnel. The<br />
nitrate is allowed to cool in the closed filter flask, which is placed in a<br />
freezing mixture in order to accelerate crystallisation. After an<br />
hour the almost colourless reaction product is thoroughly separated<br />
by nitration at the pump, and is washed several times with 50 per<br />
cent alcohol, to which a small quantity <strong>of</strong> aqueous sulphurous acid<br />
has been added, until the filtrate is no longer alkaline. By rapid<br />
recrystallisation from a not too large volume <strong>of</strong> hot alcohol the<br />
hydrazobenzene is obtained quite colourless and pure. Melting point<br />
(with production <strong>of</strong> a yellow colour) 124°. Because <strong>of</strong> its great tendency<br />
to undergo autoxidation hydrazobenzene should be thoroughly<br />
dried in vacuo, and then can only be preserved for any length <strong>of</strong> time<br />
in a colourless condition if kept in well-closed containers in an atmosphere<br />
<strong>of</strong> CO2 or N2 or, better, in sealed tubes. This tendency to<br />
oxidation also requires the preparation being carried through without<br />
interruption.<br />
The yield <strong>of</strong> crude product, which can be used directly for further<br />
preparations, amounts to 20-25 g.<br />
(b) AZOBENZENE PROM HYDRAZOBENZENE<br />
1. By Dehydrogenation.—Bromine (10 g., 3-2 c.c.) is dropped<br />
into a solution <strong>of</strong> 6-0 g. <strong>of</strong> sodium hydroxide in 75 c.c. <strong>of</strong> water
AZOBENZENE 185<br />
(75 c.c. <strong>of</strong> 22V-sodium hydroxide solution) which is kept cool in ice.<br />
Hydrazobenzene (9-2 g., 0-05 mole) in 60 c.c. <strong>of</strong> ether is shaken for<br />
ten minutes in a small separating funnel with this hypobromite<br />
solution, the ether layer is separated from the aqueous and the ether<br />
is distilled. Orange-red platelets <strong>of</strong> azobenzene, which melt at 68°<br />
when recrystallised from a little alcohol, are thus obtained. Yield<br />
quantitative.<br />
Azobenzene is also obtained in good yield by drawing air through<br />
an alkaline alcoholic solution <strong>of</strong> hydrazobenzene for several hojirs.<br />
2. By Dismutation.—Hydrazobenzene (1-2 g.) is melted in a test<br />
tube over a small flame. The orange-red liquid thus produced is<br />
carefully heated until the aniline which has beenformed begins to boil.<br />
On cooling, a semi-solid mixture <strong>of</strong> red azobenzene and aniline is obtained.<br />
The aniline can be shaken out with water and identified by<br />
means <strong>of</strong> the bleaching powder reaction. The azobenzene may be<br />
recrystallised from alcohol as described above. If it is desired to<br />
isolate the aniline also, when larger amounts <strong>of</strong> hydrazobenzene are<br />
used, the base is separated from the azobenzene by means <strong>of</strong> dilute<br />
acetic acid. From the solution <strong>of</strong> its acetate the aniline is then<br />
liberated with concentrated alkali hydroxide solution, extracted<br />
with ether, and purified in the manner already described.<br />
Azobenzene, which contains the chromophore group —N=N—, and<br />
is the parent substance <strong>of</strong> the azo-dyes, is a very stable compound,<br />
capable <strong>of</strong> being distilled without decomposition. The group N=N<br />
between the two aromatic nuclei is very firmly bound, although in most<br />
other azo-compounds this is not the case. The fastness <strong>of</strong> the azo-dyes<br />
is thus explained.<br />
With concentrated mineral acids azobenzene gives red salts, as may<br />
be shown by pouring hydrochloric acid on it. Addition <strong>of</strong> hydrogen<br />
leads to the re-formation <strong>of</strong> the hydrazo-compound. Oxygen is added<br />
on and the azoxy-compound formed by the action <strong>of</strong> hydrogen peroxide<br />
or nitric acid. The synthesis <strong>of</strong> asymmetrical aromatic azo-compounds<br />
from nitroso-compounds and primary amines was discussed above.<br />
At its melting point hydrazobenzene decomposes into azobenzene<br />
and aniline in the manner shown in the equation :<br />
H»Cr-NH HN—C.H, HKC..N H.N.C.H.<br />
X 5 5 V A 5<br />
H5C6—NH HN—OeH8 H5C6.N H2N.C6<br />
An exactly similar reaction <strong>of</strong> phenylhydrazine will be discussed later<br />
(p. 296). A simple example <strong>of</strong> this type is provided by the spontaneous<br />
decomposition <strong>of</strong> hydrogen peroxide into oxygen and water :
186 BBNZIDINB FKOM HYDEAZOBBNZBNB<br />
OH OH 0 HOH<br />
! t\ - • I +<br />
OH OH 0 HOH<br />
The spontaneous decomposition <strong>of</strong> hydrazobenzene, like that <strong>of</strong><br />
hydrogen peroxide, is catalytically accelerated by metallic platinum.<br />
(c) BENZIDINE FROM HYDEAZOBENZENE<br />
Hydrazobenzene (9-2 g.) dissolved in the minimum quantity <strong>of</strong><br />
ether is added drop by drop with shaking to 100 c.c. <strong>of</strong> ice-cold,<br />
approximately 7 N-hydrochloric acid (concentrated acid diluted<br />
with an equal volume <strong>of</strong> water). Crystalline benzidine hydrochloride<br />
separates and, after 50 c.c. <strong>of</strong> concentrated hydrochloric acid have<br />
been added and the mixture has stood for half an hour, the hydrochloride<br />
is filtered at the pump, and washed, first with 7 2V-hydrochloric<br />
acid and then with a little ether. Yield 9-10 g. The<br />
hydrochloride can be recrystallised by dissolution in hot water<br />
and addition <strong>of</strong> concentrated hydrochloric acid to the slightly<br />
cooled solution.<br />
To obtain the free base a slight excess <strong>of</strong> concentrated sodium<br />
hydroxide solution is added to a not too concentrated solution <strong>of</strong> the<br />
salt prepared by dissolving the latter in warm water containing a<br />
little hydrochloric acid, and cooling rapidly to 15°-20°. The base,<br />
which separates in crystalline form, is filtered with suction and<br />
thoroughly washed with water. Before the alkali is added the<br />
solution <strong>of</strong> the salt must be clear ; any hydrochloride which has been<br />
precipitated must be removed by filtration.<br />
The free benzidine can be recrystallised from hot water or else<br />
from a little alcohol. Melting point 122°.<br />
The conversion <strong>of</strong> hydrazobenzene into the isomeric benzidine—<br />
discovered by the Russian chemist Zinin in the year 1846—is started<br />
catalytically by mineral acids and results from the tendency <strong>of</strong> the<br />
molecule to pass into a form possessing less energy, i.e. into a more<br />
saturated condition. The reaction is suitably classified with those <strong>of</strong><br />
which the chief characteristic is that a substituent united to nitrogen<br />
exchanges its point <strong>of</strong> attachment with an H-atom <strong>of</strong> the nucleus—<br />
usually an H-atom in the y-position. To this class belong the conversion<br />
<strong>of</strong> phenylsulphaminic acid into sulphanilic acid (p. 198), <strong>of</strong> phenylhydroxylamine<br />
into y-aminophenol (p. 176), and also <strong>of</strong> acetanilide<br />
into y-aminoacetophenone and <strong>of</strong> N-chloroacetanilide into y-chloroacetanilide<br />
:
THE BBNZIDINB KBAKKANGBMBNT<br />
HH HH<br />
H< •N.CO.CH,<br />
\_/ H<br />
HH HH<br />
N.CO.CH3 —><br />
Cl<br />
Cl..<br />
NH2<br />
.NH.CO.CH3 .<br />
The rearrangement <strong>of</strong> aromatic nitrosamines to be discussed later is<br />
also <strong>of</strong> this type, e.g.<br />
•N.CHa<br />
NO<br />
In the same way, in the benzidine reaction, the group HN.C6H6<br />
becomes separated from nitrogen and attaches itself as HaN.C6H4 to<br />
the y-position left free by the hydrogen atom.<br />
187<br />
NH,<br />
Special attention must be drawn to the fact that the radicles which<br />
wander do not do so as " free radicles ", but that the movements <strong>of</strong><br />
these groups take place within the range <strong>of</strong> the molecular forces.<br />
The similarity <strong>of</strong> the rearrangement <strong>of</strong> aromatic hydrazo-compounds<br />
to the exchange reactions with which they were compared above becomes<br />
more marked in those cases where the y-positions <strong>of</strong> the two benzene<br />
nuclei are occupied. Then, as a rule, a diphenyl base is not produced,<br />
but the radicle which separates moves so that its nitrogen atom takes<br />
up the o-position with respect to the other nitrogen atom ; derivatives<br />
<strong>of</strong> o-aminodiphenylamine are thus produced, e.g.<br />
NH<br />
H3C<br />
This form <strong>of</strong> the isomerisation is known as the semidine transformation<br />
(P. Jacobson).<br />
Benzidine, and the diphenyl bases tolidine and dianisidine which are<br />
produced in the same way from o-nitrotoluene and o-nitroanisole, are
188 KBDUCTION OF NITKOBBNZBNB<br />
manufactured on a large scale in the dye industry, as important intermediates<br />
for the preparation <strong>of</strong> substantive azo-dyes (which dye cotton<br />
directly, cf. in this connexion pp. 300, 302).<br />
H2N<br />
CH3 or OCH3<br />
On the Mechanism <strong>of</strong> the Reduction <strong>of</strong> Nitrobenzene<br />
The reduction <strong>of</strong> aromatic nitro-compounds is <strong>of</strong> exceptionally great<br />
interest, not only scientifically, but also technically. The conversion<br />
<strong>of</strong> the hydrocarbons <strong>of</strong> coal tar into useful products began with the<br />
discovery <strong>of</strong> the nitration process; the conversion, on the technical<br />
scale, <strong>of</strong> the nitro-group <strong>of</strong> nitrobenzene into the amino-group gave<br />
aniline, the starting material for the preparation <strong>of</strong> innumerable dyes<br />
and pharmaceutical products; to aniline were added the homologous<br />
toluidines, xylidines, naphthylamines, and so on.<br />
The production <strong>of</strong> aniline from nitrobenzene proceeds in such a way<br />
that the reactive hydrogen is added to the nitro-group, the oxygen is<br />
eliminated as water, and finally hydrogen is again added on. The process<br />
is not a simple one and involves a series <strong>of</strong> intermediate stages :<br />
CHS.N^ 4 2H<br />
H<br />
^OH<br />
•^1 +2H<br />
^ C « H - N \OH ^i£ QANH,.<br />
/8-Phenylhydroxylamine<br />
Under the conditions prevailing during the production <strong>of</strong> aniline<br />
neither nitrosobenzene nor phenylhydroxylamine is encountered. The<br />
reason for this is that the rate <strong>of</strong> reduction <strong>of</strong> these intermediate products<br />
is much greater than that <strong>of</strong> the nitrobenzene itself (F. Haber).<br />
In neutral or alkaline solution the conditions are altered so as to<br />
favour the immediate precursor <strong>of</strong> the final product <strong>of</strong> hydrogenation,<br />
namely, phenylhydroxylamine. This compound is obtained from nitrobenzene,<br />
suspended in ammonium chloride solution, by reduction with<br />
zinc dust. Zinc dust can decompose water with the formation <strong>of</strong><br />
Zn(0H)2 if a substance is present which takes up the liberated hydrogen.<br />
Molecular, i e. ordinary, oxygen is capable <strong>of</strong> doing this and is thereby<br />
converted into hydrogen peroxide (M. Traube) :<br />
—>• Zn(OH)2 + H2O2.
AZOXYBBNZBNB TO HYDKAZOBENZENE 189<br />
In the case under discussion the nitrobenzene takes the place <strong>of</strong> the<br />
oxygen. (Write the equation.) If the experiment is properly carried<br />
out, the reduction is limited in this way to the phenylhydroxylamine<br />
If the reduction takes place in an alkaline medium, products derived<br />
from two molecules <strong>of</strong> nitrobenzene are formed. In these products<br />
the unaltered portions <strong>of</strong> the nitrobenzene molecules are united by<br />
means <strong>of</strong> nitrogen atoms. These substances are :<br />
C6HS.N:N.C6H5 Azoxybenzene,<br />
0<br />
C6H5.N:N.C6H5 Azobenzene,<br />
CgH5.NH.NH.C6H5 Hydrazobenzene.<br />
The least powerful method <strong>of</strong> reduction, boiling nitrobenzene with<br />
sodium methoxide in solution in methyl alcohol, provides azoxybenzene<br />
in excellent yield (Zinin); the methoxide is converted into formate.<br />
(Write the equation.)<br />
Since azoxybenzene is attacked by more powerful reducing agents,<br />
e.g. zinc dust and sodium hydroxide solution or ammonia, the use <strong>of</strong><br />
such agents converts nitrobenzene to azobenzene and hydrazobenzene,<br />
by passing at once beyond the azoxybenzene stage. The three reduction<br />
products with " paired " nitrogen atoms, therefore, stand in very<br />
close genetic relation to each other.<br />
Experiment. Reduction <strong>of</strong> Azoxybenzene to Hydrazobenzene.—<br />
Azoxybenzene (1 g.) is dissolved in 5 c.c. <strong>of</strong> alcohol, the solution is<br />
heated to boiling, and 3 c.c. <strong>of</strong> 50 per cent sodium hydroxide solution<br />
and 2-3 g. <strong>of</strong> zinc dust are added with shaking. At first the mixture<br />
becomes red, because <strong>of</strong> the formation <strong>of</strong> azobenzene, but on more<br />
prolonged boiling a colourless solution is obtained just as in the<br />
reduction <strong>of</strong> nitrobenzene. When this stage has been reached, the<br />
mixture is filtered with suction through a small Biichner funnel and<br />
the hydrazobenzene is finally isolated in the manner described on<br />
p. 183 et seq.<br />
Thus the joining <strong>of</strong> the two molecules by nitrogen takes place when<br />
azoxybenzene is formed, and the experiment described on p. 182 shows<br />
quite definitely that this substance is produced with extraordinary ease<br />
from phenylhydroxylamine and nitrosobenzene in the presence <strong>of</strong><br />
alkali, that is to say, under the conditions which prevail during the production<br />
<strong>of</strong> the whole series. Nitrosobenzene is the first stage, but cannot<br />
be isolated, for in the course <strong>of</strong> the reaction it is trapped by the phenylhydroxylamine<br />
as soon as it is formed.<br />
An explanation is thus provided <strong>of</strong> the otherwise puzzling formation
190 AZOXYBBNZBNB TO HYDKAZOBBNZBNB<br />
<strong>of</strong> important products with paired nitrogen atoms during the reduction<br />
<strong>of</strong> aromatic nitro-compounds. The technical importance <strong>of</strong> the process<br />
concerns the synthesis <strong>of</strong> benzidine and <strong>of</strong> analogous bases.<br />
The electrolytic reduction <strong>of</strong> nitrobenzene can be carried out conveniently<br />
according to the methods described by K. Elbs in Vbungsbeispidefilr<br />
die elektrolytische Darstellung chemischer Praparate<br />
8., 1911).
CHAPTBK IV<br />
8ULPH0NIC ACIDS<br />
1. BENZENE MONOSULPHONIC ACID FROM BENZENE AND<br />
SULPHURIC ACID<br />
BENZENE (45 c.c. =O5 mole) is gradually added in small portions to<br />
150 g. <strong>of</strong> liquid fuming sulphuric acid containing 5-8 per cent <strong>of</strong><br />
anhydride ; no fresh portion is run in until the previous one, which<br />
first floats on the surface <strong>of</strong> the acid, has been dissolved by shaking.<br />
The acid is contained in a 200-c.c. flask which is kept cool with water<br />
and is shaken well throughout. The time required for the sulphonation<br />
is about ten to fifteen minutes. The reaction mixture is run<br />
slowly from a dropping funnel into a beaker containing three to four<br />
times its volume <strong>of</strong> cold saturated brine kept cool with ice and stirred<br />
while the mixture is added. After some time the sodium benzene<br />
sulphonate separates in the form <strong>of</strong> lustrous nacrous plates and on<br />
prolonged standing forms a thick crystalline sludge. (Crystallisation<br />
may be started by scratching the beaker with a glass rod.) The<br />
sludge is filtered at the pump and the crystals are pressed with a<br />
cork or glass stopper and then washed twice with a little saturated<br />
sodium chloride solution. Finally, the salt is dried in air on filter<br />
paper or on porous plate, powdered, and heated to 110° in a drying<br />
oven until it forms a dry dust. The yield is about 100 g., but the<br />
material contains sodium chloride.<br />
Of the crude product 5 g. may be purified by recrystallisation<br />
from absolute alcohol. (The admixed sodium chloride is insoluble<br />
in alcohol.)<br />
To isolate the diphenylsulphone, which is produced as a byproduct,<br />
30 g. <strong>of</strong> the powdered salt are warmed with 50 c.c. <strong>of</strong> ether,<br />
the mixture is filtered with suction while hot and the undissolved<br />
material is washed with ether. The ether leaves on evaporation a<br />
small quantity <strong>of</strong> a crystalline residue which is recrystallised from<br />
ligroin in a test tube. Melting point 129°.<br />
191
192 BBNZBNBSULPHONAMIDB<br />
To prepare benzenesulphonyl chloride 60 g. (0-33 mole) <strong>of</strong> the<br />
sodium salt are heated for a quarter to half an hour on a vigorously<br />
boiling water bath in a fume chamber with 80 g. <strong>of</strong> finely powdered<br />
phosphorus pentachloride. The reaction product is cooled and then<br />
poured slowly into a separating funnel containing 600 c.c. <strong>of</strong> icewater.<br />
In order to decompose the phosphorus oxychloride, the<br />
funnel is repeatedly shaken, and after standing for one hour the<br />
sulphonyl chloride is extracted with ether. The ethereal solution is<br />
dried over a little calcium chloride, the ether is evaporated, and the<br />
residue is distilled in vacuo. The bulk passes over at 120°-124°/12<br />
mm. Pure benzenesulphonyl chloride solidifies when cooled in icewater.<br />
Benzenesulphonamide.—Finely powdered ammonium carbonate<br />
(10 g.) and benzenesulphonyl chloride (about 1 c.c.) are ground in a<br />
porcelain basin which is then warmed over a small flame until the<br />
odour <strong>of</strong> the sulphochloride has disappeared ; the mixture is well<br />
stirred meanwhile. After cooling, water is added and the product is<br />
collected at the pump, washed several times with water, and then<br />
crystallised from alcohol by adding hot water until a turbidity<br />
appears. Melting point 156°.<br />
Benzenesulphohydroxamic Acid. 1 -—Hydroxylamine hydrochloride<br />
(10 g.) is boiled under reflux condenser with just enough methyl<br />
alcohol to dissolve it, and when still hot is decomposed by a solution<br />
<strong>of</strong> 3 g. <strong>of</strong> sodium in 60 c.c. <strong>of</strong> ethyl alcohol, which should not be<br />
added too quickly. After the mixture has been cooled, precipitated<br />
sodium chloride is removed at the pump and 8-5 g. <strong>of</strong> benzenesulphonyl<br />
chloride are then added in small portions to the solution <strong>of</strong><br />
free hydroxylamine. Most <strong>of</strong> the alcohol is now removed by distillation<br />
from the water bath, the hydroxylamine hydrochloride<br />
which has separated is removed by filtration, and the filtrate is<br />
evaporated to dryness in vacuo at a moderate temperature. The<br />
residue is extracted three times with 15 c.c. portions <strong>of</strong> boiling<br />
absolute ether. Evaporation <strong>of</strong> the combined ethereal extracts in<br />
an open dish yields the benzene sulphohydroxamic acid in the<br />
form <strong>of</strong> a mass <strong>of</strong> crystalline plates which are digested with cold<br />
chlor<strong>of</strong>orm and filtered with suction. Yield 5-6 g. Melting point<br />
126°.<br />
The homologous tolyl compound is prepared in a similar way from<br />
1 Piloty, Ber., 1896, 29, 1559.
TOLUENE-^-SULPHONIC ACID 193<br />
toluene y-sulphochloride, which is a cheap commercial by-product in<br />
the manufacture <strong>of</strong> saccharin.<br />
The most important reaction <strong>of</strong> benzenesulphohydroxamic acid is<br />
its decomposition by alkalis. This decomposition does not consist in a<br />
reversal <strong>of</strong> the process <strong>of</strong> formation (i.e. conversion into benzenesulphonic<br />
acid and hydroxylamine). An exchange <strong>of</strong> the state <strong>of</strong> oxidation<br />
takes place : benzenesulphinic acid and nitroxyl are produced :<br />
C6H5.SO2.NHOH^<br />
or C6H5.8(O):NOH I «_ C6H5.SO2H + O:NH .<br />
OH i<br />
Advantage is taken <strong>of</strong> this decomposition in carrying out the Angeli-<br />
Eimini test for aldehydes (p. 214).<br />
2. TOLUENE-p-SULPHONIC ACID 1<br />
In the processes described under 1 and 3 the sulphonating agent<br />
used is concentrated sulphuric acid in excess and therefore the product<br />
<strong>of</strong> the reaction is isolated in the form <strong>of</strong> its sodium salt. The<br />
method now to be described, on the other hand, permits <strong>of</strong> the direct<br />
isolation <strong>of</strong> the free sulphonic acid. Such isolation is possible because<br />
<strong>of</strong> the fact that the water formed in the reaction is removed by distillation<br />
in an ingenious apparatus (Fig. 52). When stoicheiometrical<br />
amounts <strong>of</strong> sulphuric acid are used, its sulphonating action<br />
is soon stopped by this water. (Hence the excess <strong>of</strong> acid in the<br />
other methods.) By the use <strong>of</strong> an excess <strong>of</strong> toluene the whole <strong>of</strong> the<br />
sulphuric acid is consumed. In the flask (capacity 0-5 1.) shown in<br />
the figure 40 c.c. <strong>of</strong> concentrated sulphuric acid (d. 1 -8) and 200 c.c.<br />
<strong>of</strong> toluene are heated to boiling on the sand bath. The hydrocarbon<br />
which distils is condensed in the condenser K, drops through a small<br />
funnel into the water-trap H which separates the flask from the<br />
condenser and is provided with a drain cock ; after the lower portion<br />
<strong>of</strong> the trap has filled, the toluene flows back into the flask. The<br />
capacity <strong>of</strong> the portion <strong>of</strong> the trap below the delivery tube is 10-15 c.c.<br />
The water produced in the reaction distils with the toluene vapour<br />
and after condensation collects under the toluene in H. To keep the<br />
lower portion <strong>of</strong> the trap cool it is enclosed in a lead coil through<br />
which flows a current <strong>of</strong> water. From time to time the water which<br />
collects is run into a small measuring cylinder. After the toluenesulphuric<br />
acid mixture has boiled for five hours, about 18 c.c. <strong>of</strong><br />
1 H. Meyer, AnnaUn, 1923, 433, 331.
194 NAPHTHALENE-/3-SULPH0NIC ACID<br />
water are obtained, partly from the sulphuric acid and partly produced<br />
in the reaction (12-5 c.c).<br />
The contents <strong>of</strong> the flask solidify when water<br />
(12-5 c.c.) is added. To remove toluene and<br />
toluene-o-sulphonic acid the solid is pressed well<br />
on porous plate, the hydrated ^-sulphonic acid<br />
which is thus obtained is dissolved in a little hot<br />
water, and three volumes <strong>of</strong> concentrated hydrochloric<br />
acid are added. The crystalline material<br />
which separates is nltered with suction on an<br />
acid-resisting filter, washed with ice-cold concentrated<br />
hydrochloric acid, and then twice<br />
recrystallised in the<br />
same way. Finally,<br />
the acid is dried in<br />
a desiccator over<br />
potassium hydroxide<br />
until completely free<br />
from hydrochloric acid.<br />
(Test a sample.)<br />
Owing to the presence<br />
<strong>of</strong> some carbon particles<br />
the crystals are<br />
slightly grey in colour.<br />
Melting point 104°-<br />
FIG. 52<br />
105°. Yield after<br />
three recrystallisations about 50 g.<br />
3. NAPHTHALENE-/3-SULPHONIC ACID<br />
A mixture <strong>of</strong> 64 g. <strong>of</strong> naphthalene and 45 c.c. (80 g.) <strong>of</strong> pure<br />
concentrated sulphuric acid is heated in an open flask in an oil bath<br />
at 170°-180° for four hours. The solution is cooled somewhat and is<br />
then cautiously poured with stirring into a litre <strong>of</strong> water and neutralised<br />
while boiling in a large basin with a sludge <strong>of</strong> lime (from about<br />
70 g. <strong>of</strong> slaked lime). The sludge should not be too thin. The<br />
neutralised material is filtered as hot as possible through a large<br />
Biichner funnel into a previously warmed filter flask. The solid on<br />
the funnel is washed three times with hot water and the filtrate<br />
(clarified, if necessary, through a folded filter paper) is evaporated<br />
in a basin over a free flame until a sample solidifies to a crystalline
SULPHANILIC ACID 195<br />
paste when rubbed with a glass rod. The concentrated solution is<br />
allowed to stand over night and the calcium naphthalene-/3-sulphonate<br />
which has separated is filtered with suction, pressed down<br />
well on the funnel, and washed with a little water. To obtain the<br />
sodium salt concentrated sodium carbonate solution is added to<br />
the hot solution <strong>of</strong> the calcium salt until the mixture is just permanently<br />
alkaline. The precipitated calcium carbonate is removed<br />
at the filter pump while the mixture is still warm, and is washed<br />
with water. The filtrate is evaporated in a basin over a naked flame<br />
until crystals begin to separate from the hot liquid. After standing<br />
for several hours in the cold, the crystals are collected, the mother<br />
liquor is further concentrated, and after standing for a long time is<br />
again filtered. The two crops <strong>of</strong> crystals are mixed and dried on<br />
the water bath. Yield 75-85 g.<br />
A very elegant process for the direct preparation <strong>of</strong> the free<br />
naphthalene-/3-sulphonic acid from its components has been described<br />
by 0. N. Witt (Ber., 1915, 48, 751). It is specially<br />
recommended as an alternative to the process described above.<br />
4. SULPHANILIC ACID FROM ANILINE AND SULPHURIC ACID<br />
Pure concentrated sulphuric acid (100 g.) and freshly distilled<br />
aniline (31 g. =0-33 mole) are gradually mixed with shaking in a<br />
dry flask and the mixture is heated at 180°-190° in an oil bath until<br />
sodium hydroxide no longer liberates aniline from a sample diluted<br />
with water (four to five hours). The reaction mixture is cooled somewhat<br />
and then poured with stirring into cold water. Sulphanilic<br />
acid crystallises, is collected at the filter pump, washed with water,<br />
and recrystallised from water with addition <strong>of</strong> animal charcoal.<br />
Yield 30-35 g.<br />
On a technical scale aniline is heated with one mole only <strong>of</strong><br />
H2S04, i.e. as acid sulphate ; the temperature is about the same<br />
as that given above. (The " baking" process.) Compare this<br />
process, which can also be used in the laboratory, with that here<br />
described.<br />
5. 2 : 4-DINITRO-a-NAPHTHOL-7-SULPHONIC ACID 1<br />
(NAPHTHOL YELLOW S)<br />
Finely powdered a-naphthol (50 g.) is added gradually to 200 g.<br />
1 G. P. 10785, Friedl&nder, I, 327.
196 SULPHONIC ACIDS<br />
<strong>of</strong> 25 per cent oleum and brought into solution by continuous shaking.<br />
The solution is then heated at 125° in an oil bath for one hour.<br />
In order to ascertain whether the a-naphthol has been completely<br />
converted into the 2:4: 7-trisulphonic acid, a sample <strong>of</strong> the solution<br />
is mixed with about 10 c.c. <strong>of</strong> water in a test tube, 10 c.c. <strong>of</strong> concentrated<br />
nitric acid are added, and the mixture is heated nearly to<br />
boiling. If the yellow solution which is thus formed neither becomes<br />
turbid nor deposits flocks on cooling, the melt can be worked up for<br />
naphthol yellow S. Otherwise the conversion <strong>of</strong> the a-naphthol into<br />
trisulphonic acid must be completed by the addition <strong>of</strong> a more concentrated<br />
oleum and renewed heating.<br />
The cooled melt is gradually mixed with 500 g. <strong>of</strong> crushed ice,<br />
the liquid thus obtained is filtered and 120 g. <strong>of</strong> nitric acid (d. 1 -4)<br />
are added to the brown filtrate, which is then heated at 50° for half<br />
an hour. After the solution has stood for twelve hours at ordinary<br />
temperature, the greater part <strong>of</strong> the dinitronaphtholsulphonic acid<br />
produced will have separated. It is filtered <strong>of</strong>f and crystallises from<br />
hot dilute hydrochloric acid in small yellow needles which are dried<br />
first on porous plate and then in a desiccator over sulphuric acid<br />
and potassium hydroxide. Melting point 151°. Yield about 85<br />
per cent <strong>of</strong> theoretical.<br />
Naphthol yellow S, called by A. Kossel " flavianic acid ", is used<br />
in the isolation <strong>of</strong> arginine (p. 404).<br />
Explanations<br />
The technical method for the sulphonation <strong>of</strong> aromatic compounds<br />
is the exact counterpart <strong>of</strong> the nitration process. In both cases the<br />
OH group <strong>of</strong> the acid, along with a hydrogen atom <strong>of</strong> the benzene ring,<br />
is eliminated and in the position vacated by this hydrogen atom the<br />
groups —NO2 and —SO3H enter. For various reasons (refer to p. 106)<br />
it is probable that an addition reaction takes place somewhat as follows,<br />
one double bond <strong>of</strong> the benzene ring being involved :<br />
+ HO SO H ^ x±r H<br />
Xl[ TT.-X \TTQA<br />
^"^s^ [XlOv/oXl XT<br />
Hk^/HOH<br />
H<br />
-TT.O -H.0 J=T < r3OHH \<br />
H<br />
H<br />
Because <strong>of</strong> the tendency to revert to the stable aromatic ring<br />
system, the intermediate product (shown in brackets) will lose water<br />
and change into benzenesulphonic acid.<br />
A comparison should always be instituted between the benzene series
SULPHONATION 197<br />
and the aliphatic olefines ; in this case they behave essentially in the<br />
same way. Ethylene indeed forms an addition compound, ethyl sulphuric<br />
acid, with concentrated sulphuric acid at a low temperature<br />
(about 50°). CH2=CH2 —> CH3.CH2.O.SO3H ,<br />
hence the H28O4 molecule is here broken up in a different way. For<br />
obvious reasons this reaction cannot take place with benzene, since it<br />
must be very readily reversible. If, however, ethylene is subjected to<br />
the action <strong>of</strong> fuming sulphuric acid, a sulphonation product, so-called<br />
carbyl sulphate, is formed just as in the case <strong>of</strong> benzene. Carbyl sulphate<br />
is derived from the alcohol sulphonic acid which is first formed<br />
by esterification with sulphuric acid and subsequent elimination <strong>of</strong> water.<br />
CH2=CH2 —> CH20H—CH2SO3H —> CH2— CH2.SO3H<br />
CH^ ^-^2<br />
> 0 SO2 (Carbyl sulphate).<br />
0—SO3H<br />
S02-0<br />
In a quite analogous way ethylene reacts with nitric-sulphuric acid,<br />
nitroethyl nitrate (p. 164) being produced. How are alkyl sulphonic<br />
acids prepared ?<br />
The ease with which the sulphonic group enters into aromatic compounds<br />
depends on the nature <strong>of</strong> the substituents present, just as it does<br />
in nitration. Benzene is rather difficult to sulphonate, toluene and<br />
naphthalene are somewhat more easy, phenols and amines very easy.<br />
The sulphonation <strong>of</strong> nitrobenzene or the further sulphonation <strong>of</strong> the<br />
benzene sulphonic acids proceeds with more difficulty, and the action<br />
<strong>of</strong> the sulphuric acid must here be intensified by increasing its SO3content.<br />
Since N02 and SO3H are substituents <strong>of</strong> the second order, a second<br />
substituent enters in the w-position. Oleum containing a high percentage<br />
<strong>of</strong> sulphur trioxide finally converts benzene into benzene trisulphonic<br />
acid. Chlorosulphonic acid condenses with aromatic hydrocarbons,<br />
giving aryl sulphochlorides.<br />
From naphthalene two monosulphonic acids are obtained, namely,<br />
naphthalene-a- and -j8-sulphonic acids :<br />
8O3H<br />
a-Acid /3-Acid<br />
Substitution reactions in the naphthalene ring take place, without<br />
exception, in the a-position, which is characterised by its high reactivity.
198 SULPHONIC ACIDS<br />
The introduction <strong>of</strong> halogen and <strong>of</strong> the nitro-group leads exclusively<br />
to the a-derivative. This is also the case with the sulphonic group.<br />
When naphthalene is sulphonated at a low temperature, such as that<br />
mentioned above, the a-sulphonic acid is produced; it can thus be prepared<br />
also on a technical scale. The j8-sulphonic acid, on the other hand,<br />
is only formed at higher temperatures when the a-acid is, to a large<br />
extent, decomposed hydrolytically into naphthalene and sulphuric acid.<br />
The equilibrium between sulphonation and hydrolysis at the temperature<br />
(170°-180°) here used lies rather to the left in the case <strong>of</strong> the a-acid,<br />
and far to the right in that <strong>of</strong> the j8-acid.<br />
Naphthalene + H2SO4 * y Sulphonic acid + H2O .<br />
But since some a-acid is always found in the reaction mixture, the j8-acid<br />
must also be subject to a hydrolytic equilibrium.<br />
Actually when naphthalene-j8-sulphonic acid is melted with sulphuric<br />
acid (containing water) small amounts <strong>of</strong> the isomeric a-acid are obtained.<br />
A similar behaviour is observed in the case <strong>of</strong> the phenolsulphonic<br />
acids and in particular in that <strong>of</strong> anthraquinone, which, in its substitution<br />
reactions, is extraordinarily like naphthalene. Anthraquinone is<br />
sulphonated with more difficulty than is naphthalene, and in consequence<br />
the conditions <strong>of</strong> increased temperature which must be applied bring<br />
about the formation <strong>of</strong> the j8-acid, the important starting point for the<br />
synthesis <strong>of</strong> alizarin. In industrial practice, however, ways and means<br />
have been found for producing also anthraquinone-a-sulphonic acid,<br />
which was formerly not readily obtainable. a-Substitution takes place<br />
when the sulphonation is catalysed by mercury 1 (R. E. Schmidt).<br />
Aniline is very easily sulphonated, for example, by heating its sulphate<br />
(" baking " process). This change recalls that <strong>of</strong> aniline acetate<br />
into acetanilide. Actually, it is very probable that an analogous product<br />
acylated at the amino-group, a sulphaminic acid, is first formed,<br />
since examples <strong>of</strong> this type <strong>of</strong> change are known, e.g. the conversion<br />
<strong>of</strong> phenylhydroxylamine to y-aminophenol and <strong>of</strong> phenylnitramine to<br />
V- NH.NO2<br />
NH2<br />
y-nitraniline. The sulphonic group may be presumed to wander to the<br />
y-position.<br />
/V-NH2.H2SO4 - H *o /\—NH.8O3H<br />
v<br />
Primary aniline sulphate Phenylsulphaminic acid Sulphanilic acid<br />
1 It seems that anthraquinone-/3-sulphonic acid is not produced by rearrangement<br />
<strong>of</strong> the a-acid.
SULPHONATION 199<br />
That this is the course <strong>of</strong> the reaction is proved by the possibility<br />
<strong>of</strong> isolating the sulphaminic acid corresponding to a-naphthylamine if<br />
mild experimental conditions are chosen. At a higher temperature the<br />
naphthylsulphaminic acid is converted into l-naphthylamine-4-sulphonic<br />
acid (naphthionic acid).<br />
In the sulphonation <strong>of</strong> aniline small amounts <strong>of</strong> the o-compound are<br />
produced along with sulphanilic acid. Aniline o-sulphonic acid, however,<br />
is <strong>of</strong> no further interest. Metanilic acid, on the other hand, is<br />
also manufactured as an intermediate in the azo-dye industry. It is<br />
obtained from nitrobenzene-m-sulphonic acid by reduction. The amino-<br />
(and hydroxy-) sulphonic acids <strong>of</strong> the naphthalene series are <strong>of</strong> the greatest<br />
technical importance. They are either diazotised themselves or serve<br />
for coupling with other diazo-compounds. In this way the most important<br />
azo-dyes are produced.<br />
The phenols are as easily sulphonated as are the aromatic amines.<br />
When polynitrophenols have to be prepared, sulphonic groups are <strong>of</strong>ten<br />
first introduced and are then easily eliminated and replaced by NO2 by<br />
the action <strong>of</strong> nitric acid. This method is used, for example, in preparing<br />
picric acid.<br />
In the sulphonation <strong>of</strong> a-naphthol, SO3H-groups are easily introduced<br />
into the 2- and 4-positions <strong>of</strong> the ring containing the OH-group.<br />
The 8O3H-groups in these positions, moreover, can be replaced by NO2.<br />
The procedure described in section 5 <strong>of</strong> the present chapter shows how<br />
a third sulphonic group is introduced. The solubility in water <strong>of</strong> the<br />
dinitronaphthol is greatly increased by the presence <strong>of</strong> this group. 2 : 4-<br />
Dinitronaphthol (Martius' yellow) and its 7-sulphonic acid were formerly<br />
amongst the most important yellow dyes for wool.<br />
The sulphonic acids <strong>of</strong> aromatic hydrocarbons are difficult to isolate,<br />
at least those <strong>of</strong> the simpler members, because they are generally easily<br />
soluble in water and do not crystallise readily. They are among the<br />
strongest organic acids, and in their affinity constants differ only very<br />
little from the strong mineral acids. Their alkaline earth salts are, in<br />
general, soluble in water, and on this property depends the method used<br />
for removing the excess <strong>of</strong> sulphuric acid which is always present in the<br />
usual process employed for preparing the acids. In the preparation <strong>of</strong><br />
naphthalene-j8-sulphonic acid described above, the excess <strong>of</strong> sulphuric<br />
acid is removed in this manner. From the alkaline earth salts the alkali<br />
salts are then easily obtained in all cases by boiling with solutions <strong>of</strong><br />
alkali carbonate. As will be shown in a preparation to be described<br />
later, these alkali salts are converted into phenols by fusion with alkali.<br />
The aromatic sulphonic acids are decomposed into hydrocarbons and<br />
sulphuric acid by hot dilute mineral acids or even by superheated steam.<br />
In example 2 (above) a direct process for obtaining free sulphonic<br />
acids is described.<br />
In the aminosulphonic acids the electrochemical character <strong>of</strong> both<br />
substituents is appreciably weakened, as it is in aminocarboxylic acids
200 SULPHONAMIDBS<br />
like glycine or anthranilic acid The influence <strong>of</strong> the sulphonic group,<br />
however, preponderates over that <strong>of</strong> the ammo-group, which is already<br />
quite feeble in aniline itself. Sulphanilic acid no longer forms salts<br />
with aqueous mineral acids, but does so easily with alkalis, against which<br />
it can be sharply titrated in aqueous solution. In the case <strong>of</strong> aliphatic<br />
amino-acids such titration is only possible in alcoholic solution (Willstatter).<br />
In the preparation <strong>of</strong> benzenesulphonic acid, diphenylsulphone is<br />
produced as a by-product. The benzene sulphonic acid which is first<br />
formed itself acts on benzene, just as sulphuric acid does, and water<br />
is eliminated :<br />
The sulphone may be regarded as a product <strong>of</strong> further sulphonation<br />
The sulphones are neutral, crystalline, indifferent substances They<br />
are also produced by energetic oxidation <strong>of</strong> sulphides. The hypnotic<br />
sulphonal (write its formula) is a double sulphone<br />
On Sulphonyl Chlorides and Sulphonamides.—The conversion <strong>of</strong> benzenesulphonic<br />
acid into its chloride and amide shows that derivatives <strong>of</strong><br />
sulphonic acids, analogous to those <strong>of</strong> carboxylic acids, can be obtained<br />
The sulpho-chlondes are much less reactive than are the chlorides <strong>of</strong><br />
the carboxylic acids , benzene sulphochlonde, for example, can be disstilled<br />
in steam almost without decomposition<br />
Amines are frequently characterised by conversion to sidfhonamides,<br />
since the latter are notable for the great ease with which they crystallise.<br />
For preparative purposes the various amines may be separated by taking<br />
advantage <strong>of</strong> their behaviour towards benzene sulphochlonde Only<br />
the primary and secondary amines react to form amides, and <strong>of</strong> these<br />
only the sulphonamides from the primary amines are soluble in alkali,<br />
so that they can be separated ; by energetic hydrolysis they are subsequently<br />
converted into sulphonic acid and amine (Hinsberg) The sulphonamides<br />
from primary bases are, therefore, acids. The salts <strong>of</strong> these<br />
amides are probably derived from an " enol " form, and salt formation<br />
is favoured by the strongly negative character <strong>of</strong> the —SO2-group.<br />
C6H5SO2NHC6H5, C6H5S/ , C6H5 SO2 N(CH3) C6H5<br />
Benzenesulphanilide | NN C6H5 Benzenesulpho-i^-methyl-<br />
ONa anilide (insoluble in alkali)<br />
Sodium salt<br />
The sweetening agent saccharin is also derived from a sulphonamide ;<br />
it is prepared from toluene-o-sulphonamide by oxidising the CH3-group<br />
to carboxyl with permanganate , ring closure is subsequently brought<br />
about by the action <strong>of</strong> concentrated hydrochloric acid :
SULPHINIC ACIDS 201<br />
V SO2.NH2 / \ SO2.NH2 /N—SO2<br />
—• ~ M > N H •<br />
)—CH3 I J—COOH<br />
C 0<br />
\/~<br />
Saccharin, as its formula shows, is acidic in virtue <strong>of</strong> its imino<br />
hydrogen atom. The soluble sweetening agent is the sodium salt.<br />
If an alkali salt <strong>of</strong> a sulphonic acid is subjected to dry distillation<br />
with potassium cyanide or potassium ferrocyanide a nitrile is obtained,<br />
C6H5.SO3K + KCN = C6HS.CN + SO3K2 .<br />
Whilst the sulphonic acids themselves cannot, in practice, be reduced,<br />
their sulphochlorides may be brought to a lower state <strong>of</strong> oxidation, that<br />
<strong>of</strong> the sulphinic acids, by treatment with metals, preferably with zinc.<br />
In this way the zinc salts <strong>of</strong> these acids are produced directly :<br />
2C6H5.8O2Cl + 2Zn > (C6Hs.8O2)2Zn + ZnCl2 .<br />
The decomposition by alkalis <strong>of</strong> benzene sulphohydroxamic acid—<br />
from benzene sulphochloride and hydroxylamine—likewise leads, as was<br />
already mentioned, to the sulphinic acid (Piloty).<br />
From the sulphochlorides, by energetic reduction with nascent<br />
hydrogen, the corresponding mercaptans are produced :<br />
C6H5.SO2C1 + 6 H —> C6HB.8H + 2 H2O + HC1.<br />
The sulphinic acids can also be reduced in this way.<br />
Thiophenol.—Benzene sulphochloride (8 g.) is allowed to run in<br />
small portions from a dropping funnel into a round-bottomed flask<br />
containing 20 g. <strong>of</strong> finely granulated tin and 50 c.c. <strong>of</strong> concentrated<br />
hydrochloric acid. During the addition <strong>of</strong> the sulphochloride and<br />
until most <strong>of</strong> the tin has dissolved, the flask, which is fitted with a<br />
double neck attachment carrying a reflux condenser, is heated on<br />
the boiling water bath. The mercaptan produced is distilled with<br />
steam and extracted from the distillate with ether. The ethereal<br />
solution is dried over sodium sulphate, the ether is removed by<br />
distillation, and the thiophenol which forms the residue is likewise<br />
distilled. It passes over as an almost colourless liquid at 173°.<br />
This extremely malodorous substance should only be prepared and<br />
used under a well-ventilated hood or in a fume chamber. In particular,<br />
the substance must not be allowed to come into contact with the hands<br />
or the clothing, since the odour clings for days.<br />
The thioalcohols have a pronounced acidic character. The alkali<br />
salts <strong>of</strong> the aliphatic mercaptans are, indeed, very largely hydrolysed<br />
by water, but the aromatic compounds, on the other hand, can be
202 THIOPHENOL<br />
exactly titrated with alkali and phenolphthalein. The yellow lead salts<br />
and the colourless mercury salts are characteristic.<br />
Experiment.-—A few drops <strong>of</strong> thiophenol are added to alcoholic<br />
solutions <strong>of</strong> lead acetate and mercuric chloride.<br />
The ease with which the hydrogen atom is detached from the sulphur<br />
is noteworthy (analogy with H2S); even atmospheric oxygen gradually<br />
converts the mercaptans into aryl or alkyl disulphides, and mild oxidising<br />
agents do so at once :<br />
2 K.SH —> E.8—S.E .<br />
Experiment.-—A few drops <strong>of</strong> thiophenol on a watch-glass are<br />
slowly evaporated to dryness on the water bath with a few cubic<br />
centimetres <strong>of</strong> very dilute ammonia solution (fume chamber). An<br />
oil remains which sets to a crystalline solid on cooling. It is phenyldisulphide,<br />
melting point 61°.<br />
On reduction the disulphides take up hydrogen and are reconverted<br />
into mercaptans.<br />
A biological example <strong>of</strong> this relationship is provided by cysteine and<br />
cystine:<br />
2 HOOC.CH . CH2<br />
HOOC.CH . CH2<br />
NH2 SH _2H NH2 S<br />
Cysteine > I Cystine .<br />
+2B^ NH28<br />
HOOC.CH. CH2<br />
Another is the behaviour <strong>of</strong> " glutathione " (Hopkins), a tripeptide<br />
in which the NH2-group <strong>of</strong> cystine (or <strong>of</strong> cysteine) is combined with a<br />
carboxyl group 1 <strong>of</strong> glutamic acid to form an amide grouping, and the<br />
carboxyl group <strong>of</strong> cystine is likewise combined with the NH2-group <strong>of</strong><br />
glycine.<br />
Cystine is one <strong>of</strong> the units from which the proteins are built up.<br />
It is prepared by acid hydrolysis <strong>of</strong> keratin (from hair or horns).<br />
The aromatic mercaptans react with chlorine to form aryl sulphur<br />
chlorides (Zincke); phenyl sulphur chloride is a deep red, very reactive<br />
liquid (Lecher) :<br />
C6HS.8H + C12 —> C6HS8C1 + HC1.<br />
From the mercaptans the sulphonic acids are re-formed by energetic<br />
oxidation.<br />
1 The one which is further from the NH2-group. Cf. Hanngton and Mead,<br />
Biochem. J., 1935, 29, 1602.
CHAPTBK V<br />
ALDEHYDES<br />
1. FORMALDEHYDE<br />
THE side tube (length about 10 cm.) <strong>of</strong> a distilling flask (capacity<br />
250 c.c.) is bent upwards at the junction with the neck <strong>of</strong> the flask.<br />
The end <strong>of</strong> the side tube, drawn out into a capillary (internal diameter<br />
1-0-1-5 mm.), is then inserted through a cork into a piece <strong>of</strong><br />
combustion tubing about 30 cm. long (Fig. 53). Within the tubing<br />
FIG. 53<br />
and about 6 cm. from the point <strong>of</strong> the capillary is a copper spiral<br />
4 cm. long. The tubing slopes upwards at a small angle and its<br />
upper end is connected with a vertical condenser, preferably <strong>of</strong> the<br />
coil type. To the lower end <strong>of</strong> the condenser there are attached two<br />
communicating receivers which, during the experiment, are almost<br />
completely immersed in a freezing mixture. The short side tube <strong>of</strong><br />
the second receiver is connected to the pump. Into the distilling<br />
1 Tollens, Ber., 1886, 19, 2133. The explanatory remarks on the preparations<br />
1-3 are collected along with the experiments on p. 210 et seq.<br />
203
204 FOKMALDBHYDB<br />
flask, which is lowered as deeply as possible into a water bath kept<br />
exactly at 46°-47°, 100 c.c. <strong>of</strong> methyl alcohol are poured. The flask<br />
is then closed with a rubber stopper, through which is inserted a glass<br />
tube reaching nearly to the bottom. Through this tube air is drawn<br />
in, and when the air is passing, the copper spiral is warmed in the<br />
flame, cautiously at first, until, when red heat is reached, the reaction<br />
sets in. The air current must now be so regulated that the<br />
spiral continues to glow quite feebly without further application<br />
<strong>of</strong> heat. If the experiment is carried out in this way there will<br />
be complete freedom from explosions. The region within which<br />
methyl alcohol-air mixtures explode is indeed reached when the temperature<br />
<strong>of</strong> the bath is too low (42°-44°), but the flame strikes back<br />
no further than the capillary tube, since the rapid current in the<br />
latter prevents further striking back. (Compare the Bunsen burner<br />
which also only strikes back if the current <strong>of</strong> gas is too slow.)<br />
The two receivers contain 110-115 c.c. <strong>of</strong> a 30 to 32 per cent<br />
formaldehyde solution after all the methyl alcohol has been evaporated.<br />
A further small quantity <strong>of</strong> formaldehyde may still be collected<br />
in a third receiver containing a little water.<br />
The following paragraph contains some points which should be<br />
considered in carrying out gaseous reactions.<br />
In order to dehydrogenate one mole <strong>of</strong> methyl alcohol 0-5 mole <strong>of</strong><br />
oxygen is required, and hence for one volume <strong>of</strong> the alcohol half as much<br />
oxygen or two and a half times as much air. The stoicheiometrical<br />
mixture must therefore contain methyl alcohol and air in the proportions<br />
(by volume) 1 : 2-5, i.e. 28-5 per cent <strong>of</strong> methyl alcohol. Since the<br />
volumes vary as the partial pressures the temperature <strong>of</strong> evaporation<br />
(<strong>of</strong> the alcohol) must be so chosen that its vapour pressure shall be<br />
28-5 per cent <strong>of</strong> the atmospheric pressure, i.e. about 210 mm. <strong>of</strong> mercury.<br />
The vapour pressures <strong>of</strong> better known substances at various temperatures<br />
are to be found in Landolt-Bornstein, Physikal-chem. Tabelten, 5th Edition,<br />
1923, and supplementary volumes i., 1927, ii. 1931, iii. 1935,1936.<br />
With the simple type <strong>of</strong> apparatus here described complete saturation<br />
<strong>of</strong> the air with methyl alcohol vapour is not reached, and hence a<br />
temperature somewhat higher than the theoretical is used.<br />
Determination <strong>of</strong> the Formaldehyde Content <strong>of</strong> the Solution<br />
obtained.-—With a pipette 5 c.c. <strong>of</strong> the solution are run into a measuring<br />
flask and diluted to 50 c.c. with water. Of the diluted solution<br />
20 c.c. are placed in a conical flask (capacity 250 c.c), 30 c.c. <strong>of</strong><br />
about 3 per cent hydrogen peroxide solution, previously made
DBTEKMINATION OF FOKMALDEHYDE 205<br />
exactly neutral to phenolphthalein, and then 30 c.c. <strong>of</strong> N-sodium<br />
hydroxide solution are added and the mixture is shaken.<br />
After a short time evolution <strong>of</strong> hydrogen sets in and becomes very<br />
vigorous ; it is accompanied by the liberation <strong>of</strong> heat, and is finally<br />
brought to completion by heating for a short time. The copied<br />
solution is then titrated with iV-hydrochloric acid solution after<br />
adding more phenolphthalein. The amount <strong>of</strong> alkali consumed gives<br />
the content <strong>of</strong> formaldehyde according to the equation:<br />
2 CH20 + H2O2 + 2 NaOH —> 2 H.COONa + H2 + 2 H2O .<br />
Thus if, for example, 22-5 c.c. <strong>of</strong> sodium hydroxide solution were<br />
used in the reaction, then the 20 c.c. ( = 2 c.c. <strong>of</strong> the original solution)<br />
contain 22-5 x 30 mg. =0-675 g. <strong>of</strong> formaldehyde, i.e. the content <strong>of</strong><br />
formaldehyde was 33-8 per cent.<br />
In this very remarkable reaction, by the addition <strong>of</strong> two moles <strong>of</strong><br />
formaldehyde to hydrogen peroxide, an intermediate product having the<br />
constitution HOH2C.O.O.CH2OH, dihydroxy methyl peroxide, is formed<br />
and can indeed be isolated in the crystalline state. It breaks up, however,<br />
extremely easily by the action <strong>of</strong> alkali into formate and hydrogen :<br />
H0H2C.0.0.CH20H + 2Na0H —> 2 H.COONa+ H2 +2 H2O.<br />
[For details <strong>of</strong> this reaction see Annalen, 1923, 431, 301.]<br />
On the determination <strong>of</strong> formaldehyde with ammonia, cf. p. 215.<br />
The simple aldehydes react with neutral sulphites to form salts <strong>of</strong><br />
aldehydesulphurous acids. In this reaction free alkali is formed, and the<br />
aldehyde content <strong>of</strong> a solution can also be determined in this way if the<br />
alkali is titrated.<br />
2. ACETALDEHYDE 1<br />
(a) FROM ETHYL ALCOHOL<br />
The most suitable flask to use for this preparation is one with a<br />
capacity <strong>of</strong> 1 -5 1. having a wide double neck <strong>of</strong> the type shown in the<br />
figure. A round flask with a not too short neck and a tightly fitting<br />
branched tube attachment will also serve. To the oblique branch a<br />
large condenser is fitted (likewise in an oblique position) and into<br />
the vertical neck a two-holed rubber stopper carrying a long dropping<br />
funnel and a delivery tube (0-4 cm. internal diameter) is inserted.<br />
The delivery tube, which reaches to the bottom <strong>of</strong> the flask,<br />
supplies carbon dioxide from a steel cylinder provided with a reducing<br />
1 Partly from Wertheim, J. Amer. Chem. Soc., 1922, 44, 2658, and Fricke and<br />
Havestadt, Z. angew. Chem., 1923, 36, 546.
206 ACBTALDBHYDE<br />
valve. To the upper end <strong>of</strong> the condenser a medium sized calcium<br />
chloride u-tube is attached, and the free end <strong>of</strong> this u-tube is then<br />
connected with a condenser <strong>of</strong> the coil type (Fig. 54). At the lower<br />
end <strong>of</strong> this second condenser two connected receivers each containing<br />
100 c.c. <strong>of</strong> absolute ether are fixed. These receivers stand in a<br />
freshly prepared ice and salt mixture, and during the experiment<br />
their temperature should not rise above -10°. Through the first<br />
condenser a very slow current <strong>of</strong> water at about 26° is passed, and by<br />
means <strong>of</strong> a cotton thread tightly held by the upper rubber stopper a<br />
thermometer is maintained in such a position inside the central tube<br />
FIG. 54<br />
<strong>of</strong> the condenser that the bulb is midway between the ends. All<br />
connexions in the apparatus must be completely gas-tight. During the<br />
experiment the coil condenser is supplied with water at 5°-10°. In<br />
winter such water may be taken direct from the tap, but in warm<br />
weather it must first be passed through an ice-cooled coil.<br />
Alcohol (125 c.c. ; 2 moles C2H5OH) is now poured into the flask<br />
along with about one-third <strong>of</strong> a mixture <strong>of</strong> 150 c.c. (270 g.) <strong>of</strong> sulphuric<br />
acid and 250 c.c. <strong>of</strong> water and this alcohol-sulphuric acidwater<br />
mixture is heated to boiling. To the main portion <strong>of</strong> the<br />
diluted sulphuric acid 100 c.c. <strong>of</strong> water are added, 200 g. <strong>of</strong> sodium<br />
dichromate are dissolved in the liquid so prepared, and the solution<br />
is poured while still warm into the dropping funnel, the delivery tube<br />
<strong>of</strong> which is completely filled. After the funnel has been fixed in<br />
position its contents are allowed to run at a moderate speed into the<br />
co,
ACBTALDBHYDB 207<br />
just-boiling mixture in the flask ; the heat produced by the reaction<br />
makes further application <strong>of</strong> external heat unnecessary. By means<br />
<strong>of</strong> a moderately rapid current <strong>of</strong> carbon dioxide the aldehyde produced<br />
is carried out <strong>of</strong> the boiling solution and so protected from<br />
further oxidation. (The vapour pressure <strong>of</strong> the acetaldehyde at the<br />
temperature <strong>of</strong> the first condenser is still sufficiently high to prevent<br />
condensation when the current <strong>of</strong> gas is rapid. Condensation takes<br />
place only in the strongly cooled receivers.)<br />
The rate <strong>of</strong> addition <strong>of</strong> the dichromate solution is so regulated<br />
that the mixture in the flask is kept constantly boiling and that the<br />
thermometer in the condenser registers 25°-30°.<br />
If the head <strong>of</strong> dichromate solution is not sufficient to overcome the<br />
pressure in the apparatus a T-tube is inserted in the carbon dioxide<br />
delivery circuit, and by means <strong>of</strong> a piece <strong>of</strong> rubber tubing a by-pass,<br />
leading into the opening <strong>of</strong> the dropping funnel, is constructed. The<br />
rubber tubing is provided with a screw-clip to be used when refilling<br />
the dropping funnel.<br />
In place <strong>of</strong> a steel cylinder a freshly filled Kipp apparatus may be<br />
used, but must be fitted with a tall tube filled with dilute hydrochloric<br />
acid in order to overcome the pressure in the rest <strong>of</strong> the apparatus.<br />
The addition <strong>of</strong> the dichromate solution is complete in half an<br />
hour, and a further period <strong>of</strong> ten minutes suffices for the complete<br />
removal <strong>of</strong> aldehyde from the flask. The receivers are then disconnected,<br />
and not till then is the valve <strong>of</strong> the CO2-cylinder closed.<br />
Since the acetaldehyde cannot be separated by fractional distillation<br />
from the ether in which it has been collected, it is converted<br />
into the crystalline aldehyde-ammonia. The contents <strong>of</strong> the two<br />
receivers are transferred to a small filter jar which is cooled in a<br />
freezing mixture, and ammonia gas is led in from a cylinder. The<br />
delivery tube for the current <strong>of</strong> ammonia is a straight calcium<br />
chloride tube with its wide end deeply submerged in the liquid. To<br />
break up the crystalline mass which is formed, this tube is frequently<br />
moved to and fro. The jar is kept covered with a clock-glass<br />
(bored), piece <strong>of</strong> cardboard, or copper gauze. On account <strong>of</strong> the<br />
ether which evaporates, all flames in the vicinity must be extinguished.<br />
If an ammonia cylinder is not available the gas is obtained by heating<br />
concentrated ammonia solution in a round-bottomed flask over a<br />
screened flame. The gas must be dried by passage through a tower<br />
containing potassium hydroxide and good quicklime. The amount <strong>of</strong><br />
ammonia required is calculated as follows (small excess).
208 ACETALDEHYDE<br />
In order to avoid using too much ammonia a calculation must be<br />
made <strong>of</strong> how many litres <strong>of</strong> the gas will be required to combine with the<br />
highest yield <strong>of</strong> aldehyde which can be expected (60 g.). This weight<br />
<strong>of</strong> aldehyde is equal to 60/44 = 1 -36 mole, and corresponds to 30 litres.<br />
(Why 1) If the effects <strong>of</strong> pressure and temperature, which on the<br />
average cause an alteration <strong>of</strong> 10 per cent, are taken into account it is<br />
evident that about 33 litres <strong>of</strong> ammonia will be required. The rate<br />
at which the ammonia escapes from the cylinder is approximately standardised<br />
once for all by determining exactly with a watch the time<br />
required for a current <strong>of</strong> reproducible velocity (fixed by counting the<br />
number <strong>of</strong> bubbles passing in unit time through a bubbler containing<br />
concentrated potassium hydroxide solution or mercury) to neutralise<br />
42 c.c. <strong>of</strong> 2V-hydrochloric acid (measuring cylinder; methyl orange).<br />
This time is the period in which, at the rate <strong>of</strong> bubbling measured, 1<br />
litre <strong>of</strong> ammonia is delivered from the cylinder.<br />
Ammonia is passed into the ethereal solution <strong>of</strong> aldehyde for<br />
about thirty times this litre period (determined above), and the mixture<br />
is left for one hour for complete crystallisation ; a sample <strong>of</strong> the<br />
liquid portion is then treated in a test tube with more ammonia gas<br />
in order to ascertain whether further precipitation occurs. If this<br />
is not so the aldehyde-ammonia is separated at the pump, washed a<br />
few times with absolute ether, and dried first on filter paper and then<br />
in a non-evacuated desiccator over sulphuric acid. If kept in a<br />
well-closed container the dry substance can be preserved for a long<br />
time ; impure material turns brown and decomposes in a few days.<br />
Yield 50-60 g.<br />
To obtain the free aldehyde 25 g. <strong>of</strong> the aldehyde ammonia are<br />
dissolved in 25 c.c. <strong>of</strong> water, a cooled mixture <strong>of</strong> water (40 c.c.) and<br />
concentrated sulphuric acid (30 c.c.) is added, and the acetaldehyde<br />
liberated is distilled from the water bath through a calcium chloride<br />
U-tube (gently warmed if the external temperature is low) and<br />
through an efficient coil condenser. In order to prevent autoxidation<br />
<strong>of</strong> the acetaldehyde the apparatus is filled with carbon dioxide<br />
before distillation, and, since the vapour pressure <strong>of</strong> the aldehyde<br />
is high, a slow current <strong>of</strong> carbon dioxide is passed again, for a short<br />
time only, at the end <strong>of</strong> the distillation. Since acetaldehyde boils<br />
at 21° the receiver, which is attached to the condenser by means<br />
<strong>of</strong> a cork stopper, must be well cooled in an ice-salt freezing<br />
mixture.<br />
For the experiments to be carried out with acetaldehyde see<br />
pp. 211 et seq.
ACBTALDBHYDB FKOM ACETYLENE 209<br />
(6) FROM ACETYLENE<br />
Although the process (a) is the only one which need be considered<br />
for laboratory purposes, the technically much more important hydration<br />
<strong>of</strong> acetylene is described here. From time to time this second process<br />
should be carried out in the laboratory. 1<br />
Mercuric oxide (5 g.) is dissolved for the most part in a still warm<br />
mixture <strong>of</strong> 110 c.c. <strong>of</strong> water and 50 c.c. <strong>of</strong> concentrated sulphuric<br />
acid. The mixture is brought into a large hydrogenation flask<br />
(Fig. 58, p. 377) and shaken for some time with acetylene prepared<br />
from calcium carbide, purified with acid solutions <strong>of</strong> dichromate and<br />
copper nitrate, and collected over saturated sodium chloride solution<br />
in a glass gas-holder (capacity 10-15 litres). Before shaking<br />
is begun the air present must be displaced by the hydrocarbon.<br />
If necessary the absorption can also be brought about in a<br />
thick-walled flask fixed in an upright position on a shaking machine ;<br />
after the air has been driven out by the acetylene the rubber stopper<br />
through which the delivery tube passes is fastened down with wire.<br />
In from eight to ten hours up to 10 1. <strong>of</strong> acetylene are taken up.<br />
The colourless intermediate mercury compound very soon begins to<br />
separate. After the passing in <strong>of</strong> acetylene has ceased the whole <strong>of</strong><br />
the reaction mixture is transferred to a round-bottomed flask and<br />
heated on a conical (Babo) air bath, while steam is passed through<br />
to decompose the mercury compound. The acetaldehyde liberated<br />
distils with the steam. An apparatus similar to that described<br />
under (a) is used; one receiver containing ether and cooled in a<br />
freezing mixture is sufficient. The aldehyde is precipitated from<br />
the ethereal solution as aldehyde-ammonia in the manner described<br />
above. Yield <strong>of</strong> aldehyde-ammonia 5-6 g.<br />
3. BENZALDEHYDE FROM BENZYLIDENE CHLORIDE<br />
Dry chlorine is led into 50 g. <strong>of</strong> boiling toluene until its weight<br />
has increased by 40 g., and the boiling point has risen to 187° ; the<br />
operation is carried out in the same way as described for the preparation<br />
<strong>of</strong> benzyl chloride (p. 100). We are merely concerned with<br />
a continuation <strong>of</strong> this same reaction.<br />
The crude benzylidene chloride so obtained is boiled for four<br />
hours in a round-bottomed flask under an efficient reflux condenser<br />
with 500 c.c. <strong>of</strong> water and 150 g. <strong>of</strong> precipitated calcium carbonate<br />
1 The procedure here described was worked out in the chemical laboratory <strong>of</strong><br />
the University <strong>of</strong> Gottingen.<br />
P
210 BENZALDEHYDE<br />
(or prepared chalk or finely powdered marble). An oil bath at 130°<br />
(thermometer in the oil) is used to heat the flask, and a gentle<br />
current <strong>of</strong> carbon dioxide is passed through the apparatus. The<br />
flask is then removed from the oil bath and steam is passed through<br />
the hot liquid to remove the benzaldehyde formed.<br />
The residue in the flask is then filtered at the pump while hot,<br />
and the filtrate is strongly acidified with concentrated hydrochloric<br />
acid. When the acid filtrate is cooled the by-product <strong>of</strong> the reaction,<br />
benzoic acid, separates in glistening plates. These are<br />
filtered with suction, and recrystallised from boiling water. Melting<br />
point 121°. Benzoic acid is somewhat volatile with steam.<br />
The distillate from the steam distillation is twice shaken with<br />
not too much ether, and the ethereal extract, if necessary after concentration,<br />
is transferred to a wide-mouthed bottle, into which<br />
technical sodium bisulphite solution is poured in small portions with<br />
stirring (a glass rod is used) so that the aldehyde addition compound<br />
formed sets to a thick paste. The bottle is then stoppered and vigorously<br />
shaken; the stopper is removed from time to time until all<br />
the benzaldehyde has entered into combination. (Odour !) The<br />
paste is now filtered with suction, and the solid on the funnel, after<br />
washing with ether, is at once decomposed by mixing it with an<br />
excess <strong>of</strong> sodium carbonate solution; the liberated aldehyde is<br />
removed without delay by steam distillation. The distillate is<br />
extracted with ether, the extract is dried over a little calcium<br />
chloride, the ether is removed by distillation, and the benzaldehyde<br />
which remains is likewise distilled. Boiling point 179°. Yield 35-<br />
40 g. (70 per cent <strong>of</strong> the theoretical).<br />
Since benzaldehyde is very sensitive to the action <strong>of</strong> oxygen, all<br />
stages <strong>of</strong> the preparation must be performed in rapid succession.<br />
Explanations and Experiments Relating to Chapter V., Sections 1-3<br />
The lowest members <strong>of</strong> the series <strong>of</strong> the aldehydes are colourless<br />
liquids <strong>of</strong> pungent odour and miscible with water ; the middle members<br />
are also liquids, but do not dissolve easily in water; the aldehydes <strong>of</strong><br />
high molecular weight are crystalline solids. The boiling points <strong>of</strong> the<br />
aldehydes are considerably lower than those <strong>of</strong> the corresponding<br />
alcohols :<br />
(CH3.CHO . . . . Boiling point 21°<br />
\CH3.CH2OH . . . „ „ 78°<br />
/CH3.CH2.CHO „ 50°<br />
\CH3.CH2.CH2OH 97°.
ALDEHYDES 211<br />
The aromatic aldehydes have a pleasant odour. (Oil <strong>of</strong> bitter<br />
almonds, vanillin, piperonal.)<br />
The most general method for the preparation <strong>of</strong> aldehydes consists<br />
in removing two hydrogen atoms from a primary alcohol (afcohol dehydrogenatus)<br />
; from secondary alcohols, in the same way, ketones are<br />
formed. Since the hydrogen is generally removed by an oxidising<br />
agent the process is regarded as an oxidation. Alcohols can, however,<br />
also be decomposed catalytically into aldehyde and hydrogen. Such<br />
decomposition is brought about by palladium black in the cold or by<br />
copper at higher temperatures. The part played by the copper in the<br />
preparation <strong>of</strong> formaldehyde (according to 0. Loew) consists in the<br />
separation <strong>of</strong> hydrogen (dehydrogenation), and the purpose <strong>of</strong> the air<br />
which is mixed with the methyl alcohol is to burn the hydrogen and<br />
upset the equilibrium:<br />
CH30H ^~~ > H2.C:0 + 2 H .<br />
Substances having triple linkages when dissolved in sulphuric acid<br />
take up the elements <strong>of</strong> water, particularly if mercuric salts are present.<br />
The simplest example <strong>of</strong> this reaction is the preparation <strong>of</strong> acetaldehyde<br />
from acetylene itself in the manner described above.<br />
H,C—CH<br />
HC=CH —> 0 —> I —> H3C.CH + HgSO4.<br />
HgO-SO2<br />
This process has great technical importance for the synthesis <strong>of</strong><br />
acetic acid.<br />
The aldehydes are readily oxidised and therefore behave towards<br />
ammoniacal silver solution and towards Fehling's solution as reducing<br />
agents.<br />
Experiment 1 .•—Dilute a few drops <strong>of</strong> formaldehyde or acetaldehyde<br />
with a few c.c. <strong>of</strong> water, add a small amount <strong>of</strong> ammoniacal<br />
silver solution, and divide the mixture between two test tubes. Into<br />
one test tube run a few drops <strong>of</strong> sodium hydroxide solution; an<br />
immediate separation <strong>of</strong> metallic silver takes place. From the<br />
other solution after standing for some time in the cold, or more<br />
quickly on warming, the silver separates. Thus the oxidising action<br />
<strong>of</strong> ammoniacal silver solution is very considerably increased by<br />
sodium hydroxide (Tollens). Also test the reducing action <strong>of</strong> the<br />
aldehydes on Fehling's solution.<br />
By oxidation aldehydes are converted into carbozylic acids. This<br />
process is indeed a direct continuation <strong>of</strong> the dehydrogenation <strong>of</strong> the
212 ALCOHOLIC FEKMENTATION<br />
alcohols. It is not the aldehyde itself but the aldehyde hydrate formed<br />
by the addition <strong>of</strong> water which actually reacts with the oxidising agent,<br />
e.g.<br />
CH3.C:O -^> CH3.c/ —% CH3.C:O + H2O .<br />
I N<br />
H<br />
The conversion <strong>of</strong> ethyl alcohol by way <strong>of</strong> acetaldehyde into acetic<br />
acid is the chemical expression equivalent to acetic fermentation. In<br />
this process the acetic bacteria utilise atmospheric oxygen in order to<br />
bind the hydrogen. That the hydrogen which has to be removed is<br />
activated, and not the oxygen (as was formerly thought), is shown by<br />
experiments in which oxygen is excluded and replaced by quinone; the<br />
bacteria produce acetic acid from alcohol as before and the quinone is<br />
reduced to hydroquinone.<br />
CH3.CH2OH + 2 O=/ = N=O+H2O—>CH3.COOH + 2 H<br />
The important part which acetaldehyde plays in alcoholic fermentation<br />
(C. Neuburg) is shown by the fact that it is formed by decarboxylation<br />
<strong>of</strong> the intermediate product, pyruvic acid :<br />
CH3.CO.COOH —> CH3.CHO+CO2.<br />
In the manner expressed by the fundamental equation :<br />
CH2OH.CHOH.CH(OH2) + CH3.CHO —> CH3.CO.COOH +<br />
Glyeeraldehyde (hydrate) CH3. CH2OH + H;O<br />
ethyl alcohol and fresh pyruvic acid are formed by mutual hydrogenation<br />
and dehydrogenation. Compare, in this connexion, p. 403.<br />
The aldehydes are liable to a pronounced extent to undergo autoxidation,<br />
i.e. to combine with molecular oxygen. Here it is the genuine<br />
H<br />
aldehyde structure •—C=O which first adds on the unsaturated oxygen<br />
molecule at the reactive double linkage, so that a per-acid is produced :<br />
H<br />
CH,.C=O<br />
+<br />
0=0<br />
H<br />
CH3.C--O<br />
. .<br />
u<br />
CH3.C=O<br />
+<br />
-OH<br />
Peracetic acid<br />
The per-acids are strong oxidising agents and react with a second<br />
molecule <strong>of</strong> aldehyde to give two molecules <strong>of</strong> acid :<br />
CH3.C=0<br />
+ O=C—CH3 —> 2 CH3.C=O .<br />
-OH H OH
AUTOXIDATION 213<br />
Thus the autoxidation <strong>of</strong> the aldehydes leads finally to acids. That<br />
a per-acid is first formed can be very easily shown in the case <strong>of</strong> acetaldehyde<br />
by the immediate liberation <strong>of</strong> iodine from potassium iodide<br />
solution which is caused by this strong oxidising agent. In the case <strong>of</strong><br />
benzaldehyde, which combines exceptionally rapidly with oxygen, it<br />
has been possible to trap the per-acid with acetic anhydride as benzoylacetyl<br />
peroxide (Nef) :<br />
C6H5.C:O C6H5.C=O<br />
I +(CH3CO)2O—> | +CH3.COOH.<br />
O—OH O—O--CO.CH3<br />
Experiment 2.-—One c.c. <strong>of</strong> freshly prepared acetaldehyde is<br />
shaken for a few minutes in a long glass cylinder provided with a<br />
tightly fitting rubber stopper. Half <strong>of</strong> the liquid is then poured into<br />
a little dilute potassium iodide solution and half into two or three<br />
volumes <strong>of</strong> water which is then tested with litmus paper to show the<br />
presence <strong>of</strong> the acetic acid formed. It will be found that the aldehyde<br />
which has been dissolved in water hardly liberates any iodine<br />
from potassium iodide solution after standing for some time.<br />
Experiment 3/—Two drops <strong>of</strong> benzaldehyde are exposed to the<br />
air on a watch-glass for one hour.<br />
For preparative purposes the method <strong>of</strong> obtaining aldehydes from<br />
the primary alcohols is preferable by far, at least in the aliphatic series.<br />
The simple aromatic aldehydes can be obtained by alkaline hydrolysis<br />
<strong>of</strong> the arybdene chlorides, R.CHC12, which are produced from the<br />
hydrocarbons by substitution with chlorine (technical method for the<br />
preparation <strong>of</strong> benzaldehyde). In addition to these methods the elegant<br />
synthesis <strong>of</strong> Gattermann and Koch should be mentioned here. This<br />
synthesis, which proceeds like that <strong>of</strong> Friedel-Crafts, consists in acting<br />
on the aromatic hydrocarbon with carbon monoxide and hydrogen<br />
chloride in the presence <strong>of</strong> aluminium chloride and cuprous chloride.<br />
H<br />
>+CO + HCl<br />
The carbon monoxide may be replaced by hydrogen cyanide (Gattermann)<br />
or by fulminic acid (in the form <strong>of</strong> mercury fulminate, Scholl),<br />
the first product then being respectively an imine or an oxime.<br />
There is no absolutely general method for converting carboxylic<br />
acids into aldehydes ; in many cases, however, the chlorine <strong>of</strong> acid<br />
chlorides can be replaced by hydrogen activated by means <strong>of</strong> palladium<br />
(Rosenmund).<br />
C6H5.C=O 2H C6H5.C=O<br />
Cl -> H
214 COLOUK KBACTIONS<br />
Another possibility, which has already been <strong>of</strong> great use in many<br />
syntheses, consists in the energetic reduction <strong>of</strong> hot esters with a little<br />
alcohol and much metallic sodium to the corresponding alcohols<br />
(Bouveault); these can then be oxidised to aldehydes in the usual way.<br />
Experiment 4.—Colour reaction with fuchsine and sulphurous<br />
acid. A fragment <strong>of</strong> fuchsine is dissolved in a large volume <strong>of</strong> hot<br />
water to form an approximately 0-2 per cent solution, and after this<br />
has been cooled, concentrated aqueous sulphurous acid is added<br />
gradually until, after standing for some time, decolorisation has<br />
taken place. The solution can be kept for a long time in a wellclosed<br />
vessel. The sensitivity <strong>of</strong> the reaction should be tested with<br />
progressively diluted solutions <strong>of</strong> formaldehyde and acetaldehyde.<br />
When testing aldehydes which, like benzaldehyde, are sparingly<br />
soluble in water, some alcohol is added. The alcohol must first be<br />
tested since, on long standing, particularly when exposed to light, it<br />
may contain detectable amounts <strong>of</strong> acetaldehyde. In the case <strong>of</strong><br />
formaldehyde the colour developed with the fuchsine solution becomes<br />
pure blue by the action <strong>of</strong> concentrated hydrochloric acid<br />
whilst with other aldehydes, under the same conditions, the colour<br />
almost completely disappears. (Distinction between formaldehyde<br />
and acetaldehyde.)<br />
The colour reaction with fuchsine-sulphurous acid provides a<br />
means <strong>of</strong> distinguishing sharply between aldehydes and ketones. In<br />
dilute aqueous solution dextrose reacts negatively. Concerning the<br />
mechanism <strong>of</strong> the colour reaction see Ber., 1921, 54, 2527.<br />
Experiment 5. Angeli-Rimini Reaction.—A few drops <strong>of</strong> an<br />
aldehyde (any <strong>of</strong> those prepared) are dissolved in aldehyde-free 1<br />
alcohol and about the same amount <strong>of</strong> benzene sulphohydroxamic<br />
acid (for the preparation <strong>of</strong> which see p. 192) is added ; in the case<br />
<strong>of</strong> aliphatic substances, twice as much <strong>of</strong> the acid is used. To this<br />
mixture, kept cool and shaken, 2 iV-sodium hydroxide is added, in<br />
an amount judged to be about two molecular proportions. After<br />
standing for fifteen minutes the alkaline mixture is made just acid<br />
to Congo red and finally a drop <strong>of</strong> ferric chloride solution is added.<br />
An intense red colour is produced.<br />
It was mentioned on p. 193 that benzene sulphohydroxamic acid is<br />
decomposed by alkali into benzene sulphinic acid and the very unstable<br />
compound nitroxyl, 0=NH. If nitroxyl is produced in the presence<br />
1 This ia naturally only important when, in actual practice, an unknown substance<br />
is to be tested as to its aldehyde character.
KBACTION WITH AMMONIA 215<br />
<strong>of</strong> an aldehyde, it adds itself to the carbonyl group and a hydrozamic<br />
acid results, the presence <strong>of</strong> which—and consequently also that <strong>of</strong> the<br />
aldehyde—is indicated by the intense colour reaction with ferric<br />
chloride.<br />
OH<br />
C6H5.C:O + HN:O —> [GaR5.C C6H5.C:NOH .<br />
H L HNNOj<br />
If the nitroxyl is formulated as hydrate, i.e. as dihydroxyammonia<br />
/OH<br />
, the similarity <strong>of</strong> this reaction to that which occurs when<br />
aldoximes are formed from aldehydes and hydroxylamine becomes<br />
still clearer. Nitroxyl is also formed in the alkaline hydrolysis <strong>of</strong> the<br />
sodium salt <strong>of</strong> aa-nitrohydroxylamine (Angeli) :<br />
O:N:NOH >- O:N.ONa + O:NH .<br />
The other reactions <strong>of</strong> the aldehydes, which are extraordinarily<br />
reactive substances, need only be mentioned here. Such reactions are :<br />
reduction to alcohols, formation <strong>of</strong> hydrazones, oximes, semicarbazones,<br />
bisulphite compounds, acetals and cyanohydrins (by addition <strong>of</strong> hydrogen<br />
cyanide).<br />
Experiment 6. Reaction with Ammonia.—Of the formaldehyde<br />
prepared 10 c.c. are mixed with a small excess <strong>of</strong> ammonia and the<br />
mixture is evaporated in a small glass dish on the water bath. The<br />
colourless crystals which remain consist <strong>of</strong> hexamethylenetetramine<br />
(CH2)6N4 (urotropine.) This reaction proceeds quantitatively. It<br />
should be so carried out and the result compared with that obtained<br />
by titration.<br />
Acetaldehyde combines with ammonia to form aldehyde-ammonia,<br />
as was shown by the method <strong>of</strong> preparation described.<br />
0 H<br />
' /<br />
(<br />
\ 2 3<br />
Benzaldehyde gives so-called hydrobenzamide<br />
C6H,.CH:NN<br />
C6H5.CH:N- >CH.C6HB .<br />
The products <strong>of</strong> the reaction with ammonia are therefore funda-
216 BISULPHITE COMPOUNDS<br />
mentally difEerent for each <strong>of</strong> the three aldehydes, but in each case the<br />
reaction begins with an addition :<br />
H H .OH<br />
—C : 0 + NH3 —> —C<<br />
The reaction with acetaldehyde does not proceed further, but with the<br />
other two water is eliminated and further changes take place.<br />
Experiment 7.—A few drops <strong>of</strong> benzaldehyde are vigorously<br />
shaken in a test tube with three parts <strong>of</strong> commercial bisulphite<br />
solution. The crystals which separate are the sodium bisulphite<br />
compound <strong>of</strong> the benzaldehyde.<br />
The bisulphite compounds are formed according to the following<br />
equation:<br />
/OH<br />
E—C:O + H8O3Na —> E—C<<br />
H H\8O3Na<br />
The problem <strong>of</strong> the constitution <strong>of</strong> the bisulphite compounds <strong>of</strong> the<br />
aldehydes and ketones seemed to have been solved in accordance with<br />
the above formula by the investigations <strong>of</strong> Easchig and Prahl. 1 It<br />
follows from their work, that these compounds are salts <strong>of</strong> a-hydroxysulphonic<br />
acids, the sulphonic groups <strong>of</strong> which are mobilised by the<br />
adjacent hydroxyl group. G. Schroeter, 2 however, has obtained from<br />
esters <strong>of</strong> dimethylmethanedisulphonic acid by hydrolytic elimination<br />
<strong>of</strong> one sulphonic group in the manner indicated below the salt <strong>of</strong> the<br />
a-hydrozyisopropylsidphonic acid and this salt is not identical with<br />
acetone sodium bisulphite.<br />
H3CX /8O3E H3CX /OH<br />
3 X /<br />
>C< +3NaOH—> >C< + Na2SO3 + 2 EOH .<br />
\8O3Na<br />
This contradiction has yet to be explained.<br />
Since the bisulphite compounds are decomposed into their constituents<br />
by warming with sodium carbonate solution or with dilute<br />
acids, they are particularly useful for enabling aldehydes (and ketones)<br />
to be separated from mixtures with other substances.<br />
Polymerisation.—The simple aldehydes polymerise very easily. Anhydrous<br />
formaldehyde, indeed, cannot be kept for long, but changes<br />
very rapidly into an amorphous solid <strong>of</strong> high molecular weight (CH2O)n,<br />
paraformaldehyde. At ordinary temperature this substance breaks<br />
down again slowly to the simple molecule, a change which takes place<br />
1 Annalen, 1926, 448, 265; Ber., 1928, 61, 179.<br />
2 Ber., 1926, 59, 2341 ; 1928, 61, 1616.
PAKALDBHYDB 217<br />
more rapidly on heating. From the aqueous solution (formalin), in<br />
which form it is usually prepared, the anhydrous aldehyde cannot be obtained,<br />
since it only begins to distil with water vapour when the solution<br />
is boiled, and even then distils very slowly. This is due to the fact that,<br />
ATT<br />
for the most part, it is present in solution as a hydrate, H 2 C < Q T T •<br />
Acetaldehyde also polymerises gradually on keeping, yielding the<br />
liquid paraldehyde (CH 3.CHO) 3, which boils without decomposition at<br />
124°. If a little hydrogen chloride is passed, with cooling, into acetal-<br />
dehyde the likewise polymeric metaldehyde crystallises out.<br />
Experiment 8.-—To 5 c.c. <strong>of</strong> freshly distilled acetaldehyde in a<br />
moderate-sized conical flask one drop <strong>of</strong> concentrated sulphuric acid<br />
is added with cooling. W h e n the vigorous reaction is over, the<br />
paraldehyde produced is shaken in a small separating funnel with<br />
water in order to r e m o v e the sulphuric acid, and the polymeride,<br />
w h i c h is insoluble in water, is separated if necessary b y extraction<br />
with ether. After being dried with a little calcium chloride the<br />
substance is distilled from a small distilling flask. Boiling point<br />
124°.<br />
Conversely paraldehyde can be reconverted into acetaldehyde b y<br />
adding a few drops <strong>of</strong> concentrated sulphuric acid a n d distilling from<br />
the water bath through a column.<br />
B y this m e a n s fresh acetaldehyde can be prepared w h e n e v e r<br />
required.<br />
Experiment 9.-—Pure paraldehyde is tested b y the previously<br />
described aldehyde reactions: with a m m o n i a c a l silver nitrate,<br />
fuchsine-sulphurous acid, a n d bisulphite solutions. All are negative.<br />
Vapour density determinations show that paraldehyde is formed b y<br />
the union <strong>of</strong> three molecules <strong>of</strong> acetaldehyde. Since the substance has<br />
no aldehydic properties the following structure, that <strong>of</strong> a cyclic triacetal,<br />
is properly given to it:<br />
CH 3<br />
C H<br />
0 0<br />
CHg.CH CH.CHg<br />
v<br />
0<br />
(Compare with this the polymerisation <strong>of</strong> acetylene to benzene.)<br />
As was seen above, a small amount <strong>of</strong> concentrated sulphuric acid
218 POLYMBKISATION<br />
effects both the polymerisation <strong>of</strong> acetaldehyde and the depolymerisation<br />
<strong>of</strong> paraldehyde. An equilibrium occurs and its attainment is catalytically<br />
accelerated by the concentrated sulphuric acid :<br />
3CH3.CHO 7~^ (CH3.CHO)3.<br />
Moderate temperatures greatly favour the displacement <strong>of</strong> the<br />
equilibrium to the right. That, nevertheless, as was mentioned above,<br />
paraldehyde can be depolymerised to acetaldehyde by sulphuric acid<br />
is due to the fact that the equilibrium is shifted in accordance with the<br />
law <strong>of</strong> mass action. Thus the denominator <strong>of</strong> the fraction in the equation<br />
Concentration <strong>of</strong> paraldehyde „<br />
(Concentration ot acetaldehyde) 3 ~<br />
always tends to decrease, owing to the continuous volatilisation <strong>of</strong><br />
the acetaldehyde present in small quantity; the re-establishment <strong>of</strong> the<br />
equilibrium brings about, a decrease in the concentration <strong>of</strong> the paraldehyde<br />
and so favours its depolymerisation. Although equilibrium<br />
is reached at a point at which the mixture consists almost entirely <strong>of</strong><br />
paraldehyde, yet because <strong>of</strong> the high vapour pressure <strong>of</strong> the monomer<br />
almost complete depolymerisation can be brought about in practice.<br />
At low temperatures a second polymeric form <strong>of</strong> acetaldehyde, the<br />
beautifully crystalline metaldehyde, is formed.<br />
Experiment 10.—A few bubbles <strong>of</strong> hydrogen chloride are passed<br />
into a solution <strong>of</strong> a few cubic centimetres <strong>of</strong> acetaldehyde in twice<br />
as much absolute ether kept cold in a freezing mixture. After a<br />
short time the metaldehyde separates in magnificent needle-shaped<br />
crystals which are filtered with suction and washed with ether. The<br />
filtrate yields a second crop on repeating the treatment.<br />
Like paraldehyde, metaldehyde can be preserved, and, when freshly<br />
prepared, is odourless. It also has no aldehydic properties. On<br />
keeping, however, a distinct odour <strong>of</strong> acetaldehyde becomes evident<br />
—a sign that here also an equilibrium is slowly being established.<br />
Metaldehyde can be completely depolymerised by heating. Molecular<br />
weight determinations (in phenol) show that metaldehyde is tetramolecular<br />
(Hantzsch); the examination <strong>of</strong> the space lattice <strong>of</strong> crystals<br />
by the method <strong>of</strong> Laue and Bragg points to the same conclusion<br />
(Mark).<br />
Metaldehyde is prepared on a technical scale for use as fuel (" solid<br />
methylated spirits ").<br />
These reversible polymerisations <strong>of</strong> aldehydes are to be distinguished<br />
from the condensations which they can also undergo. Thus formaldehyde<br />
is converted by quite weak alkalis (Ca(OH)2, CaCO3) into glycollic<br />
aldehyde and glyceraldehyde, and further into a mixture <strong>of</strong> hexoses<br />
(Butlerow, 0. Loew) from which E. Fischer isolated the so-called
CONDENSATION 219<br />
a-acrose (dl-iiuctose). In such condensations several molecules combine<br />
with the formation <strong>of</strong> new carbon-carbon linkages. Recall the part<br />
played by formaldehyde in the assimilation <strong>of</strong> carbon dioxide.<br />
The so-called aldol condensation, which all aldehydes <strong>of</strong> the formula<br />
*R<br />
j£>CH.CHO undergo under the influence <strong>of</strong> dilute alkalis or acids,<br />
also involves the formation <strong>of</strong> new carbon-carbon linkages. The hydrogen<br />
atom in the a-position possesses mobility induced by the adjacent<br />
CO-group, and this mobilised hydrogen atom combines with the likewise<br />
very reactive C=O-group <strong>of</strong> a second molecule :<br />
H 4, OH<br />
O=CH.CH2 + O=CH.CH3 —> O=CH.CH2.CH.CH3.<br />
V___^' Aldol<br />
The aldols are ^-hydroxyaldehydes and, like all ^-hydroxycarbonylcompounds,<br />
they easily lose water and become converted into a-/3unsaturated<br />
aldehydes. From aldol as starting material a technical<br />
route to butadiene is provided and possibly, in the future, to a synthetic<br />
rubber.<br />
Experiment 11.—A few drops <strong>of</strong> acetaldehyde, dissolved in<br />
about 2 c.c. <strong>of</strong> water, are heated in a test tube with 0-5 c.c. <strong>of</strong> dilute<br />
sodium hydroxide solution. A yellow colour develops and the<br />
acetaldehyde is converted by way <strong>of</strong> aldol into crotonaldehyde, which<br />
can be recognised in the boiling solution by its pungent odour. If<br />
acetaldehyde is heated with concentrated alkali solution yellow<br />
aldehyde resin is precipitated as a result <strong>of</strong> further condensation.<br />
The brown colour which develops in solutions <strong>of</strong> ethoxides and <strong>of</strong><br />
potassium hydroxide in ethyl alcohol is to be attributed to the formation<br />
<strong>of</strong> similar substances, following oxidation <strong>of</strong> the alcohol.<br />
The benzoin reaction and the reaction <strong>of</strong> Cannizzaro, which are discussed<br />
later, likewise take place because <strong>of</strong> the tendency <strong>of</strong> the aldehydes<br />
to undergo condensation. The specific catalyst determines in each case<br />
the particular way along which the condensation will proceed.<br />
Experiment 12. Schardinger's Reaction.—Of two 25 c.c. portions<br />
<strong>of</strong> fresh milk one is boiled for a short time and cooled; then<br />
1 c.c. <strong>of</strong> the formaldehyde (prepared in an earlier experiment) and a<br />
few drops <strong>of</strong> an aqueous solution <strong>of</strong> methylene blue are added to each<br />
portion. When the two samples are now warmed to about 50° the<br />
dye in the unboiled milk is very rapidly decolorised and the same<br />
happens to further amounts added. In the boiled milk the colour<br />
remains unaltered.
220 CANNIZZAKO'S KB ACTION<br />
Fresh cows' milk contains an enzyme which very greatly accelerates<br />
the reduction by aldehyde <strong>of</strong> methylene blue to its leuco-compound.<br />
This reduction does not show itself if the enzyme is absent. Two H-<br />
/OH<br />
atoms <strong>of</strong> the hydrated aldehyde R—C^-OH are " activated " by the<br />
X H<br />
enzyme in such a way that the aldehyde acts as a reducing agent and is<br />
thereby itself converted into acid. Finely divided metallic platinum<br />
can produce the same result as does the enzyme (Bredig) Heat destroys<br />
the effect <strong>of</strong> Schardinger's aldehyde-dehydrase For details see<br />
Ber., 1914, 47, 2085 ; Annalen, 1929, 477, 32.<br />
Technical Importance <strong>of</strong> the Aldehydes.—Formalin solution is used<br />
as a disinfectant and as a preservative. Caseinogen hardened with<br />
formaldehyde is a widely used substitute for vulcanite, as is also the<br />
synthetic resin bakehte, which is produced by the condensation <strong>of</strong><br />
formaldehyde with phenol (p. 243).<br />
Sodium hyposulphite (hydrosulphite) is converted by aldehydes into<br />
aldehyde bisulphite compound and aldehyde sulphoxylate :<br />
/H M<br />
(SO2Na)2 + 2 R CHO + H2O —> R C^-OH<br />
X<br />
SO3Na<br />
+ R C^-OH<br />
X SO2Na<br />
The sulphoxylate obtained from formaldehyde is much used as a<br />
reducing agent in discharge printing in dyeworks.<br />
Small amounts <strong>of</strong> acetaldehyde (from acetylene) are converted industrially<br />
into alcohol by catalytic hydrogenation, and large amounts<br />
are transformed into acetic acid by catalysed autoxidation (with oxides<br />
<strong>of</strong> manganese)<br />
Benzaldehyde is an important intermediate for dyes (see malachite<br />
green); many other aldehydes (phenylacetaldehyde, vanillin, piperonal,<br />
citral, etc ) are used in perfumery or as flavouring agents.<br />
4. CANNIZZARO'S REACTION. BENZOIC ACID AND BENZYL<br />
ALCOHOL FROM BENZALDEHYDE 1<br />
Freshly distilled benzaldehyde (20 g.) is shaken in a stoppered<br />
cylinder or in a thick-walled flask with a cold aqueous solution <strong>of</strong><br />
potassium hydroxide (18 g. in 12 g. <strong>of</strong> water) until a permanent<br />
emulsion is formed. The container is corked and left over night.<br />
To the crystalline paste (potassium benzoate) which separates, just<br />
sufficient water 2 is added to enable the benzyl alcohol to be ex-<br />
1 Ber., 1881, 14, 2394.<br />
2 If too much ia added it is difficult to extract the (water-soluble) benzyl alcohol<br />
completely.
CANNIZZAKO'S KBACTION 221<br />
tracted by repeated shaking with ether. The combined ether<br />
extracts are concentrated to 30-40 c.c. and are then thoroughly<br />
shaken twice in a separating funnel with 5 c.c. portions <strong>of</strong> commercial<br />
(40 per cent) bisulphite solution. After the ethereal solution has<br />
been separated, freed from dissolved sulphurous acid by shaking<br />
with a few cubic centimetres <strong>of</strong> sodium carbonate solution, and dried<br />
with anhydrous sodium sulphate, the ether is removed by distillation<br />
and the benzyl alcohol then passes over at 206°. Yield <strong>of</strong><br />
benzyl alcohol about 8 g.<br />
The aqueous alkaline liquid (from which the benzyl alcohol was<br />
removed with ether) is acidified with hydrochloric acid. Benzoic<br />
acid is precipitated and, when cold, is filtered <strong>of</strong>f with suction. It<br />
is recrystallised from boiling water without previous washing.<br />
Melting point 121°. Yield 9-10 g.<br />
Cannizzaro's reaction probably proceeds in such a way that two<br />
molecules <strong>of</strong> aldehyde condense to form an ester which is then hydrolysed<br />
to alcohol and acid :<br />
A<br />
+ HOH2C—R.<br />
This view is supported by the fact that aldehydes are actually condensed<br />
to esters by aluminium ethoxide (Tistschenko).<br />
The dismutation <strong>of</strong> aldehyde to acid and alcohol also plays an<br />
important part in cell metabolism, particularly in alcoholic fermentation<br />
(p. 403) (Mechanism ?) although the chemical process is certainly<br />
different in this case.<br />
The Cannizzaro reaction is by no means confined to aromatic aldehydes.<br />
Formaldehyde undergoes the same change, yielding formic acid<br />
and methyl alcohol. That the aliphatic aldehydes from acetaldehyde<br />
upwards do not undergo the reaction is due to the fact that the aldol<br />
condensation (mentioned above), in virtue <strong>of</strong> its much greater velocity,<br />
takes precedence over the Cannizzaro reaction.<br />
In the case <strong>of</strong> tertiary aldehydes, which cannot undergo the aldol<br />
condensation, the Cannizzaro reaction replaces it also in the aliphatic<br />
series. Thus glyoxylic acid is dismuted into glycollic and oxalic acids.<br />
Related to the Cannizzaro reaction there is a reaction discovered by<br />
Meerwein, 1 in which an aldehyde is converted into an alcohol by the<br />
action <strong>of</strong> aluminium ethoxide.<br />
1 Annakn, 1925, 444, 221
222 BENZOIN AND BBNZIL<br />
Aldehydes E.CHO react with A1(OC2HS)3 in such a way that<br />
/OC2H5<br />
addition takes place and E.Cr-Oal is formed. 1 In the second stage<br />
/<br />
<strong>of</strong> the reaction this substance is decomposed into R.Cs—Oal + OHC.CH3.<br />
By means <strong>of</strong> this reduction process it is possible to obtain, from the<br />
corresponding aldehydes, alcohols such as trichloroethyl alcohol or<br />
cinnamyl alcohol, which are not otherwise readily accessible or are<br />
otherwise inaccessible. Tnbromoethyl alcohol (" avertin "), an important<br />
narcotic, is prepared in this way (F. F. Nord). It is given<br />
by the rectum.<br />
5. ACYLOIN CONDENSATION. BENZOIN FROM<br />
BENZALDEHYDE<br />
Freshly distilled benzaldehyde (10 g.) is mixed with 25 c.c. <strong>of</strong><br />
alcohol and a solution <strong>of</strong> 2 g. <strong>of</strong> potassium cyanide in 5 c.c. <strong>of</strong> water.<br />
The mixture is boiled on the water bath under reflux for one hour.<br />
Then the product is allowed to cool slowly, and the crystals which<br />
form, after being separated by filtration and washed with a little<br />
alcohol, are dried on the water bath. In order to obtain some quite<br />
pure benzoin a small sample <strong>of</strong> the crude product is recrystallised<br />
from a little alcohol. Melting point 134°. Yield about 90 per cent<br />
<strong>of</strong> the theoretical.<br />
BENZIL FROM BENZOIN<br />
The crude benzoin, prepared as above, after being dried and<br />
finely powdered, is heated (with frequent shaking) in an open flask<br />
on a vigorously boiling water bath for 1-5 to 2-0 hours with twice<br />
its weight <strong>of</strong> pure concentrated nitric acid. The reaction mixture<br />
is then diluted with cold water and when the material which separates<br />
has solidified the liquid is poured <strong>of</strong>f, and the solid, after being dried<br />
on porous plate, is crystallised from alcohol. The crystals, after<br />
filtration, are dried in air on filter paper. Melting point 95°. Yield<br />
about 90 per cent <strong>of</strong> the theoretical.<br />
The so-called acyloin or benzoin condensation is a further interesting<br />
aldehyde reaction. In the aromatic series it takes place as a result <strong>of</strong><br />
the action <strong>of</strong> potassium cyanide, and it is very probable that the potassium<br />
compound <strong>of</strong> the cyanohydrin is formed as an intermediate pro-<br />
1 al=Al/3.
THE ACYLOIN CONDENSATION 223<br />
duct. As in the case <strong>of</strong> benzyl cyanide (p. 260), there is here a labile<br />
H-atom which, in an alkaline medium, is capable <strong>of</strong> undergoing a<br />
species <strong>of</strong> aldol condensation with a second molecule <strong>of</strong> aldehyde :<br />
.OK H<br />
C6H5.C:O ±5^. C6H5.C< +O:C.C6HS<br />
H HMJ-N -f.<br />
OK H _KCN<br />
> C6HS.C C.C6H5 _^_ C6H5.CO.CHOH.C6H5.<br />
CiN OH<br />
The condensation product is then converted, with elimination <strong>of</strong><br />
potassium cyanide, into benzoin. The catalytic participation <strong>of</strong> the<br />
potassium cyanide is obvious. The distinction between this reaction<br />
and the cyanohydrin synthesis should be thoroughly grasped.<br />
Substitution products react like benzaldehyde itself (anisaldehyde<br />
gives anisoin). Similarly furfural gives furoin. (Write out the equation.)<br />
The reason why the acyloin synthesis is especially characteristic <strong>of</strong><br />
aromatic aldehydes, depends on the circumstance that in the aromatic<br />
series the tertiary carbon atom in the ring does not allow <strong>of</strong> the aldol<br />
condensation, a reaction for which conditions are otherwise much more<br />
favourable. The simplest example <strong>of</strong> the acyloin condensation, moreover,<br />
was already encountered in the case <strong>of</strong> formaldehyde (p. 218) ;<br />
glycollic aldehyde is the simplest acyloin. Acyloin compounds are also<br />
produced, in the aliphatic series, by the action <strong>of</strong> sodium or potassium<br />
on esters, and hence are also formed as by-products in the acetoacetic<br />
ester synthesis (Bouveault, Scheibler).<br />
Finally, agents which assist the acyloin synthesis have been discovered<br />
in the living cell; these enzymes (so-called carboligases) bring<br />
about the union <strong>of</strong> two molecules <strong>of</strong> aldehyde in the manner <strong>of</strong> the acyloin<br />
synthesis. Thus in fermenting yeast added benzaldehyde is caused<br />
to combine with acetaldehyde, the intermediate product <strong>of</strong> the fermentation,<br />
to form C6H5.CHOH.CO.CH3, the (optically active) benzacetoin.<br />
If acetaldehyde itself is added (instead <strong>of</strong> benzaldehyde) acetoin is<br />
formed (Neuberg). The acyloins, being a-hydroxyketones, are to some<br />
extent related to the ketoses. Thus they also reduce Fehling's solution<br />
and are converted by phenylhydrazine into osazones.<br />
Experiment.-—Benzoin (1 g.) in concentrated alcoholic solution<br />
is boiled for some time on the water bath with 1-5 c.c. <strong>of</strong> phenylhydrazine.<br />
On cooling the osazone <strong>of</strong> benzil crystallises. Melting<br />
point 225°.<br />
The production <strong>of</strong> the ammonia during the reaction should be<br />
demonstrated and the equation for the process written out.
224 BENZOIN, BBNZIL, AND BENZILIC ACID<br />
An identical compound is formed from benzil by the action <strong>of</strong><br />
phenylhydrazine, and from benzaldehyde phenylhydrazone by autoxidation<br />
(Busch). The formation <strong>of</strong> osazones from a-hydroxyketones (and<br />
a-hydroxyaldehydes) will be discussed later (p. 298).<br />
The preparative importance <strong>of</strong> the acyloins depends on the fact<br />
that they are intermediate products, from which many 1: 2-diketones<br />
can be obtained. The simplest aromatic member <strong>of</strong> this group is<br />
benzil (anisil and furil are analogous); like its aliphatic prototype<br />
diacetyl CH3.CO.CO.CH3 (and like anhydrous glyoxal) it is yellow in<br />
colour. Diacetyl is obtained from methyl-ethyl ketone via the monoxime<br />
<strong>of</strong> the former compound (von Pechmann). It is remarkable that<br />
diacetyl condenses to y-xyloquinone. (Formulate).<br />
That the two C : O-groups <strong>of</strong> these diketones are adjacent is proved<br />
by the fact that they are capable <strong>of</strong> condensing with o-phenylenediamine<br />
(quinoxalines, Hinsberg).<br />
Experiments—About 0-1 g. each <strong>of</strong> benzil and benzoin are dissolved<br />
in a test tube in 10 c.c. <strong>of</strong> alcohol and a few drops <strong>of</strong> alkaline<br />
hydroxide solution are added in the cold. A fine red colour is at<br />
once produced and disappears when the liquid is shaken with air.<br />
The colour reappears after a short time and can be caused to disappear<br />
by renewed shaking ; these changes may be brought about<br />
repeatedly. When, after a feW more drops <strong>of</strong> alkali have been added,<br />
the colour does not reappear there is no more benzoin left in the<br />
solution. Quite pure benzil does not give the colour.<br />
This remarkable reaction occurs because alkalis (potassium hydroxide)<br />
convert benzoin partly into the di-enol form, i.e. into the potassium<br />
derivative <strong>of</strong> stilbenediol C6H5.COK : COK.CeHg. 1<br />
If water is excluded this potassium salt can be isolated in the form<br />
<strong>of</strong> orange-yellow crystals which, with benzil, yield the red solution<br />
sensitive to the action <strong>of</strong> air. The solution probably contains the<br />
potassium-benzil radicle which is also obtained by the addition <strong>of</strong> metallic<br />
potassium to benzil (Beckmann and Paul, 2 Schlenk 3 ):<br />
C6H5.C_C.C6H5 + C6H5.CO.CO.C6H5 —> 2 C6H5.CO-C.C6H5<br />
OK OK OK<br />
The radicle is converted by autoxidation partly into benzil, partly<br />
into benzoic acid. 4<br />
1 a<br />
Scheuing, Annalen, 1924, 440, 72.<br />
Annalen, 1891, 266, 23.<br />
3<br />
Ber., 1913, 46, 2840.<br />
4<br />
Compare, in this connexion, A. Weiasberger, H. Mainz, and E. Strasser,<br />
Ber., 1929, 62, 1942.
THE PINACOLINE KEAKKANGEMENT 225<br />
The most important reaction <strong>of</strong> benzil and related compounds is<br />
the benzilic acid rearrangement discovered by J. von Liebig.<br />
Experiment. 1 -—Benzil (5 g.) is heated for ten minutes to boiling<br />
on the water bath with 15 c.c. <strong>of</strong> alcohol and a solution <strong>of</strong> 5 g. <strong>of</strong><br />
potassium hydroxide in 10 c.c. <strong>of</strong> water. After cooling, the suspension<br />
<strong>of</strong> potassium benzilate crystals is filtered as dry as possible by<br />
suction, and the salt, after being washed with a little alcohol, is<br />
dissolved in 20-30 c.c. <strong>of</strong> cold water. The solution is filtered and<br />
dilute sulphuric acid is added, at the boiling point, to the clear<br />
nitrate. The free acid is precipitated partly in the form <strong>of</strong> crystals.<br />
It is separated by filtration with suction while hot and washed with<br />
hot water. It can then be recrystallised at once from a large volume<br />
<strong>of</strong> hot water or, after drying, from benzene. Yield about 4 g.<br />
The first stage <strong>of</strong> the rearrangement, which proceeds according to<br />
the equation Q JJ<br />
C6H6.CO.CO.C6H5 + KOH —>• 6 ^COH.COOK ,<br />
consists in the addition <strong>of</strong> a molecule <strong>of</strong> alkali hydroxide to the benzil<br />
(Scheuing). In this addition product, evidently because <strong>of</strong> the tendency<br />
<strong>of</strong> the potassium to become neutra.1, the C6H5- and OK-groups<br />
exchange places : Q JJ<br />
•CoHs T>- CRHK.C.<br />
C6H5.C.CO.C6H5 —> C8HB.C.CO .<br />
HO OK^I HO OK<br />
By a similar reaction phenanthraquinone yields biphenyleneglycollic<br />
acid. (The equation should be written.) The benzilic acid<br />
rearrangement also plays a part in many other reactions (croconic<br />
acid, purpurogallin).<br />
The so-called pinacoline rearrangement is closely related :<br />
CH3v /CH3 CH3X<br />
CH/ I I \CH3 CH/ |<br />
AH A)H<br />
!Hq X<br />
3 OH OH<br />
Pinacone<br />
CH3<br />
C.CH3<br />
0<br />
Pinacoline<br />
1 After H. von Liebig, Ber., 1908, 41, 1644.
226 BOKNBOL AND CAMPHBNB<br />
Here also formally OH exchanges its place with an alkyl radicle,<br />
CH3, although actually—since concentrated sulphuric acid is used—<br />
the elimination <strong>of</strong> water between the two OH-groups provokes the<br />
wandering <strong>of</strong> a methyl .group.<br />
A rearrangement which takes place in similar compounds, and<br />
has been much studied recently, may be briefly mentioned here.<br />
This rearrangement has been named—not quite correctly—the retropinacoline<br />
rearrangement.<br />
It consists in the conversion <strong>of</strong> pinacolyl alcohol into tetramethylethylene<br />
with elimination <strong>of</strong> water:<br />
-C CH, ~<br />
CH<br />
Ha CH, CH3<br />
°,<br />
1 y \<br />
CH, H 0H Closely related to this change is the conversion <strong>of</strong> borneol and its<br />
derivatives into compounds <strong>of</strong> the camphene type :<br />
CH CH CH<br />
CH,<br />
' CMe21 CHOH<br />
CH,<br />
Borneol Camphene<br />
The only difference between the two reactions evidently consists<br />
in the shift <strong>of</strong> the double bond in respect <strong>of</strong> the methyl group, from<br />
a, b, to b, c. For between a and b, through stereochemical reasons, no<br />
double bond can exist, since, in accordance with Bredt's rule, none <strong>of</strong><br />
the C-atoms which are common to both rings <strong>of</strong> a bicyclic system <strong>of</strong> the<br />
camphene type can take part in an unsaturated linkage.<br />
Further inspection shows the second <strong>of</strong> the above camphene formulae<br />
to be merely another and more convenient way <strong>of</strong> writing this hydrocarbon.<br />
Information about this important work, which can be considered<br />
only briefly here, is to be derived from the publications <strong>of</strong> H. Meerwein.<br />
A clear and comprehensive review <strong>of</strong> our knowledge <strong>of</strong> molecular rearrangements<br />
is to be found in : Henrich, Theorien der organischen<br />
Ghemie, 5th Ed., 1924, Chap. XVII. See also W. Hiickel, Theoretische<br />
Grundlagen der organischen Ghemie, Leipzig, 1931, Vol. I. p. 210.<br />
Only one more rearrangement <strong>of</strong> benzil, leading to an elegant preparative<br />
method, need be mentioned here, namely its conversion into
MANDELIC ACID 227<br />
diphenylketene by the method <strong>of</strong> G. Schroter (Ber., 1909, 42, 2346). The<br />
hydrazone <strong>of</strong> benzil is dehydrogenated with mercuric oxide (preferably<br />
prepared by the experimenter himself) to yield the diazo-compound, the<br />
so-called " azibenzil " (Curtius, Staudinger) :<br />
TJ<br />
C<br />
r\{\ ri ri IT , ri IT fif\ p ri rr<br />
6±ls.bU.U.U6±ls > U6±ls.bU.U.UR±lK .<br />
N.NH2<br />
When this substance is heated in benzene with the exclusion <strong>of</strong> air<br />
and moisture, nitrogen is eliminated and the rest <strong>of</strong> the molecule undergoes<br />
rearrangement to diphenylketene:<br />
C H<br />
C6H5.CO.C.C6H5 —> O=C=c/ 6 S .<br />
/ \ N3.HB<br />
/ \ 0 0<br />
This interesting derivative <strong>of</strong> ketene is also obtained from benzilic<br />
acid by the old process <strong>of</strong> Staudinger : the acid is converted, by the<br />
action <strong>of</strong> phosphorus pentachloride, into diphenylchloracetyl chloride<br />
from which the two chlorine atoms are removed by means <strong>of</strong> zinc.<br />
(Formulate this equation.) What is carbon suboxide ? For information<br />
about the ketenes see H. Staudinger, Die Ketene, Stuttgart, 1912.<br />
Benzilic acid is dehydrogenated by lead tetra-acetate (method <strong>of</strong><br />
Criegee) giving C02 and benzophenone. Here the acid acts like a glycol.<br />
Carry out the experiment in the manner described on p. 117 and isolate<br />
the benzophenone by digesting with a little petroleum ether, the oily<br />
residue which remains after the glacial acetic acid has been evaporated<br />
in a vacuum.<br />
6. ADDITION OF HYDROGEN CYANIDE TO AN ALDEHYDE.<br />
MANDELIC ACID FROM BENZALDEHYDE<br />
Mandelic Nitrile.—Freshly distilled benzaldehyde (15 g.) is stirred<br />
with a glass rod in a cylinder with about 50 c.c. <strong>of</strong> a concentrated<br />
solution <strong>of</strong> sodium bisulphite until a paste <strong>of</strong> the addition compound<br />
/H<br />
C6HS.C^-OH has formed. The cylinder is then closed with a<br />
X SO3Na<br />
rubber stopper and vigorously shaken. The bisulphite compound<br />
is now separated by nitration at the pump, pressed well together on<br />
the filter funnel, and washed several times with small quantities <strong>of</strong><br />
ice-water. It is stirred to a thick paste with water and a cooled<br />
solution <strong>of</strong> 12 g. <strong>of</strong> pure potassium cyanide in 25 c.c. <strong>of</strong> water is<br />
added. After a short time, and especially if the mixture is stirred,<br />
the crystalline material dissolves and the mandelic nitrile appears<br />
i
228 HYDKOLYSIS OF THE NITKILB<br />
as an oil which is separated in a tap funnel from the aqueous solution<br />
and immediately used for the next stage <strong>of</strong> the preparation.<br />
Hydrolysis <strong>of</strong> the Nitrite.-—The nitrile, mixed in a porcelain basin<br />
with four times its volume <strong>of</strong> concentrated hydrochloric acid, is<br />
heated on the water bath until an abundant separation <strong>of</strong> crystals<br />
begins to take place on the surface <strong>of</strong> the liquid. The reaction<br />
mixture is then allowed to stand over night in a cool place, and the<br />
crystals which have been deposited, after being rubbed with a little<br />
water, are separated at the filter pump and washed with water (not<br />
too much). A further quantity <strong>of</strong> the acid is obtained from the<br />
filtrate by extraction with ether. The crude mandelic acid is pressed<br />
on a porous plate, dried, and purified by crystallisation from benzene.<br />
Melting point 118°. Yield about 10-15 g.<br />
Resolution <strong>of</strong> Inactive Mandelic Acid into its Active Components. 1<br />
A mixture <strong>of</strong> 10 g. <strong>of</strong> crystallised mandelic acid and 20 g. <strong>of</strong> crystallised<br />
cinchonine is heated with 500 c.c. <strong>of</strong> water jn an open flask,<br />
which is very frequently shaken, on a vigorously boiling water bath<br />
for one hour. After cooling, undissolved material is separated by<br />
filtration (but not subsequently washed with water). A few crystals<br />
<strong>of</strong> cinchonine rf-mandelate (see below) are then dropped into the clear<br />
solution (a), which is now allowed to stand in a cool place (6°-8°; in<br />
summer in the ice-chest, in winter conveniently in a cellar) for one or<br />
several days as required. The crude cinchonine rf-mandelate which<br />
thus separates is collected by filtration with suction (filtrate A, to be<br />
kept) and recrystallised from 20 parts <strong>of</strong> hot water. If the solution<br />
is seeded with a few crystals <strong>of</strong> cinchonine rf-mandelate the salt<br />
crystallises in a purer form under the same conditions as those<br />
described above. In order to obtain the free rf-mandelic acid the<br />
purified salt is dissolved in water (not too much) and a slight excess<br />
<strong>of</strong> ammonia is added. Cinchonine is precipitated and, after being<br />
filtered <strong>of</strong>f, can be recrystallised from dilute alcohol and used again<br />
for another resolution. The filtrate, which contains ammonium<br />
rf-mandelate, is acidified with hydrochloric acid and shaken with<br />
ether. When the material left on evaporation <strong>of</strong> the ether is<br />
heated for some time on a watch-glass on the water bath, it solidifies<br />
on cooling to crystals <strong>of</strong> rf-mandelic acid, which are pressed on a<br />
porous plate and recrystallised from benzene. Melting point<br />
133°-134°.<br />
Pure Z-mandelic acid is not easily obtained from small amounts <strong>of</strong><br />
1 Cf. Ber., 1883, 16, 1773 and 1899, 32, 2385.
ALANINB 229<br />
rfZ-mandelic acid. However, a feebly laevo-rotatory preparation is<br />
obtained as follows : The filtrate A is treated as has just been described<br />
for pure cinchonine rf-mandelate, and the free acid thus<br />
obtained must be laevo-rotatory since part <strong>of</strong> ^-modification has<br />
been removed.<br />
Of the three products so obtained, namely : (1) inactive racemic<br />
acid, (2) pure rf-acid, and (3) impure Z-acid, aqueous solutions <strong>of</strong><br />
suitable concentration should be prepared. The rotations <strong>of</strong> the<br />
solutions should then be determined with a polarimeter.<br />
If cinchonine d-mandelate is not available a specimen suitable for<br />
the inoculation in the first experiment is prepared as follows : To a few<br />
cubic centimetres <strong>of</strong> the solution (a) saturated aqueous sodium chloride<br />
solution is added drop by drop until slight precipitation occurs. The<br />
mixture is then heated until the precipitated material has dissolved,<br />
after which the solution is allowed to stand until crystals have been<br />
deposited, which may require a day. The "crystals consist <strong>of</strong> cinchonine<br />
hydrochloride on which a small amount <strong>of</strong> cinchonine d-mandelate<br />
is deposited, enough, however, to induce the separation <strong>of</strong> further<br />
quantities <strong>of</strong> the d-salt.<br />
7. ALANINE 1<br />
Freshly distilled acetaldehyde (13-2 g. ; 0-3 mole) dissolved in<br />
100 c.c. <strong>of</strong> ether is poured into a pressure bottle containing a cold<br />
saturated aqueous solution <strong>of</strong> 18 g. <strong>of</strong> ammonium chloride ; then<br />
a solution <strong>of</strong> 20 g. <strong>of</strong> sodium cyanide in 30 c.c. <strong>of</strong> water is added<br />
slowly drop by drop from a tap funnel with shaking and ice-cooling.<br />
The closed bottle is then agitated at ordinary temperature for three<br />
hours on a shaking machine. The contents <strong>of</strong> the bottle are next<br />
transferred to a round-bottomed flask (capacity 0-51.) which is kept<br />
cool in ice, while 100 c.c. <strong>of</strong> concentrated hydrochloric acid are added<br />
in small portions. (Fume chamber ! Free hydrocyanic acid !)<br />
The ether is removed by distillation through a downward condenser<br />
and the aqueous solution, after being heated for one hour longer on<br />
the boiling water bath, is transferred to a basin and evaporated to<br />
dryness. (A brown colour develops in the aqueous solution after the<br />
ether has been removed.) When the material in the basin is completely<br />
dry and free from hydrochloric acid (test the odour) it is<br />
extracted twice with 100 c.c. <strong>of</strong> boiling alcohol in a small roundbottomed<br />
flask. The filtered alcoholic extracts are evaporated to<br />
1 A. Strecker, Annalen, 1850, 75, 30; Zelinsky and Stadnikov, Ber., 1908,<br />
41, 2061.
230 ALANINB<br />
dryness and the extracted material is finally dried in vacua on the<br />
water bath. The alanine hydrochloride is now freed from admixed<br />
sodium chloride by dissolution in 100 c.c. <strong>of</strong> hot absolute alcohol to<br />
which 5 c.c. <strong>of</strong> ether have been added and subsequent evaporation to<br />
dryness, once again, <strong>of</strong> the alcoholic solution <strong>of</strong> the alanine salt.<br />
This salt, which is difficult to prepare in the crystalline condition, is<br />
converted into the free acid in the following way :<br />
The hydrochloride is washed into a beaker with 100 c.c. <strong>of</strong> water<br />
and boiled with 40-50 g. <strong>of</strong> litharge, added in small portions, until<br />
no more ammonia is evolved (about ten to fifteen minutes). The<br />
ammonia is derived from ammonium chloride, <strong>of</strong> which a little is<br />
present in the solution. The mixture is now filtered with suction<br />
while hot, the material on the filter being washed with 20-30 c.c. <strong>of</strong><br />
hot water, and the clear brown filtrate is freed from lead by passing<br />
hydrogen sulphide into the hot liquid. The lead sulphide is separated<br />
at the pump, and the filtrate, while still lukewarm, is shaken in<br />
a glass-stoppered bottle with about 3 g. <strong>of</strong> freshly precipitated and<br />
carefully washed silver carbonate in order to remove all chlorine<br />
ions (derived from the slightly soluble lead chloride). (A sample <strong>of</strong><br />
the treated solution should be tested for chlorine.) During the<br />
shaking the stopper <strong>of</strong> the bottle should be removed from time to<br />
time. The filtered solution, into which hydrogen sulphide is again<br />
passed, leaves alanine in the form <strong>of</strong> a dark-coloured syrup when<br />
evaporated. When this syrup is rubbed with absolute alcohol it<br />
crystallises; the crystals, after standing for some time, are separated<br />
at the pump, washed successively with a little absolute alcohol<br />
and absolute ether, and dried in a vacuum desiccator. Yield 15-<br />
20 g. Alanine can be recrystallised, but only with great loss, from<br />
its own weight <strong>of</strong> water. It is better to dissolve it in the minimum<br />
amount <strong>of</strong> boiling water and to add alcohol at the boiling point until<br />
crystallisation begins. Melting point 264° decomp.<br />
Remarks on Sections 6 and 7.—The method here described for the<br />
synthesis <strong>of</strong> cyanohydrins—treatment <strong>of</strong> the bisulphite compound <strong>of</strong><br />
the aldehyde with potassium cyanide—cannot be used in all cases.<br />
Concentrated solutions <strong>of</strong> hydrocyanic acid or anhydrous hydrogen<br />
cyanide are <strong>of</strong>ten used. The general method for the synthesis <strong>of</strong> aamino-acids,<br />
the nitriles <strong>of</strong> which are formed by the union <strong>of</strong> ammonium<br />
cyanide with aldehydes or ketones (Strecker), is to be contrasted with<br />
that for the synthesis <strong>of</strong> a-hydroxy acids. For additional amino-acid<br />
syntheses see Chap. VII. 2, p. 276.
MOLBCULAK ASYMMBTKY 231<br />
The amygdalin <strong>of</strong> bitter almonds and <strong>of</strong> other stone-fruits is the<br />
glucoside formed by the combination <strong>of</strong> 2-mandelic nitrile and gentiobiose<br />
(see p. 398). This glucoside belongs to the class <strong>of</strong> jS-glucosides,<br />
since it is hydrolysed by the enzyme emulsin yielding two molecules<br />
<strong>of</strong> dextrose, benzaldehyde, and hydrocyanic acid. Natural 2-mandelic<br />
acid was first obtained by Liebig, who subjected amygdalin to acid<br />
hydrolysis.<br />
The cyanohydrin synthesis has been applied in the study <strong>of</strong> the<br />
sugars by H. Kiliani, who used it in the synthesis <strong>of</strong> higher members <strong>of</strong><br />
the class. The carboxylic acids which result from the hydrolysis <strong>of</strong><br />
the nitriles can be reduced, in the form <strong>of</strong> their lactones, to the corresponding<br />
aldehydes.<br />
C N<br />
HC=O<br />
HC=O<br />
HCOH<br />
HOGH<br />
HCOH<br />
HCOH<br />
CH2OH<br />
«!-Glucose<br />
H C O H<br />
H C O H<br />
— > H O C H<br />
1<br />
!OH<br />
HCOH<br />
CH OH<br />
H 2 O H<br />
HCOH<br />
HCOH<br />
--»• H O C H<br />
H O O H<br />
H C O H<br />
C H 2 O H<br />
« ! - G l u c o h e p t o s e<br />
I n t h e s y n t h e s i s o f m a n d e l i c n i t r i l e d e s c r i b e d a b o v e a s y m m e t r y i s<br />
p r o d u c e d i n o n e c a r b o n a t o m , b u t e x a c t l y e q u a l n u m b e r s o f m o l e c u l e s<br />
o f t h e t w o a n t i p o d e s a r e f o r m e d , s i n c e t h e r e i s j u s t a s m u c h c h a n c e t h a t<br />
o n e s h o u l d b e f o r m e d a s t h e o t h e r .<br />
P h<br />
> C = O <<br />
P h x<br />
T h e d - a n d I - v a r i e t i e s d i f f e r o n l y i n c r y s t a l f o r m a n d i n d i r e c t i o n o f<br />
t h e r o t a t i o n ; i n a l l o t h e r p h y s i c a l a n d i n a l l c h e m i c a l p r o p e r t i e s t h e y<br />
b e h a v e e x a c t l y a l i k e . T h e s a l t s w h i c h t h e t w o f o r m s y i e l d w i t h a n<br />
1 T h e c o m p o u n d h a v i n g t h e o p p o s i t e c o n f i g u r a t i o n H O C H i s p r o d u c e d a t t h e<br />
s a m e t i m e , b u t n o t , a s i n t h e p r o d u c t i o n o f a s i m p l e r a c e m i c s u b s t a n c e , i n e q u a l<br />
a m o u n t . T h e a s y m m e t r y a l r e a d y p r e s e n t e x e r t s a d i r e c t i n g i n f l u e n c e w h i c h<br />
f a v o u r s o n e o f t h e t w o c o n f i g u r a t i o n s .<br />
O H<br />
) H<br />
C N
232 PBKKIN'S SYNTHESIS. CINNAMIC ACID<br />
optically active base, however, are no longer related to each other as<br />
object and mirror-image, and hence differences in physical constants, e.g.<br />
in solubility, appear. How are racemic bases resolved ?<br />
Enzymes exhibit specificity as regards their behaviour towards<br />
stereo-isomerides. Pasteur's biological resolution <strong>of</strong> racemic acid with<br />
moulds depends on this fact, and such moulds may also be used for the<br />
resolution <strong>of</strong> racemic mandelic acid, for the partial digestion <strong>of</strong> racemic<br />
polypeptides according to E. Fischer's method, and in numerous other<br />
processes.<br />
8. PERKIN'S SYNTHESIS<br />
CINNAMIC ACID FROM BENZALDEHYDE AND ACETIC<br />
ANHYDRIDE<br />
In a flask to which a long (about 80 cm.) wide air condenser<br />
is fitted, freshly distilled benzaldehyde (21 g., 0-2 mole), acetic<br />
anhydride (30 g.), also freshly distilled and powdered anhydrous<br />
sodium acetate (10 g.) (cf. p. 127) are heated at 180° for eight hours<br />
(beginning in the morning) in an oil bath. When the reaction has<br />
ceased the hot mixture is poured into a large flask which is washed<br />
out with water ; steam is then blown through until benzaldehyde<br />
ceases to be carried over. Sufficient water is now added to dissolve<br />
the cinnamic acid. A small amount <strong>of</strong> oily impurity remains<br />
undissolved. The solution is boiled for a short time with animal<br />
charcoal and filtered. On cooling, cinnamic acid separates from the<br />
filtrate in shining plates. If the melting point <strong>of</strong> the material thus<br />
obtained is not correct, recrystallisation from hot water is necessary.<br />
Melting point 133°. Yield about 15 g.<br />
Perkin's synthesis proceeds according to the general principle <strong>of</strong><br />
aldehyde condensations, namely, with the elimination <strong>of</strong> water formed<br />
from the carbonyl oxygen and two hydrogen atoms from a methylene<br />
or methyl group. The conditions for the synthesis depend on the reactivity<br />
<strong>of</strong> this group ; with acid or alkali as catalyst, aldehydes react<br />
even in the cold with aldehydes or ketones, but if the aldehyde is to<br />
react with an acid anhydride a high temperature is required, with an<br />
alkali salt as condensing agent. 1<br />
The difference in the conditions under which the reaction takes place<br />
is to be traced to the slight reactivity <strong>of</strong> the methyl (or a-methylene)<br />
group in the acid anhydride.<br />
Both CH2-groups <strong>of</strong> succinic acid are capable <strong>of</strong> taking part in condensations.<br />
If unsaturated aldehydes such as cinnamaldehyde are<br />
1 See Kalinin, Helv. Chim. Ada, 1928, 11, 977.
CAKOTBNOIDS 233<br />
used, with lead oxide as catalyst, highly unsaturated dicarboxylic acids<br />
are obtained which are transformed by loss <strong>of</strong> 2 CO2 into coloured<br />
" polyenes " (E. Kuhn *).<br />
H2C.CO2H C6H5.CH:CH.CH:C.!CO2|H<br />
2 C6HS.CH:CH.CHO + I • >- | " .<br />
H2C.CO2H C6H5.CH:CH.CH:C.|CO2|H<br />
When the trebly unsaturated aldehyde<br />
C6HS.CH=CH.CH=CH.CH=CH.CHO<br />
is used, this synthesis leads to the copper-coloured hydrocarbon C28H26,<br />
which contains eight conjugated double bonds.<br />
The interesting group <strong>of</strong> compounds called carotenoids consists <strong>of</strong><br />
purely aliphatic polyenes. Carotene itself, C40HB6, the colouring matter<br />
<strong>of</strong> carrots, contains eleven conjugated double bonds, and its isomeride<br />
lycopene from tomatoes and hawthorn has thirteen. Xanthophyll<br />
C40Hs6O2 (Willstatter), which occurs in nature along with chlorophyll,<br />
and the isomeride <strong>of</strong> xanthophyll, zeaxanthin (Karrer), the yellow<br />
colouring matter <strong>of</strong> maize, are closely related to these hydrocarbons.<br />
Other members <strong>of</strong> this class are carboxylic acids <strong>of</strong> the polyenes, such<br />
as the crocetins <strong>of</strong> saffron (Karrer) and bixin, the red compound from<br />
Bixa orellana (Kuhn). Physaliene, the red colouring matter <strong>of</strong> the Cape<br />
gooseberry and winter cherry, is dipalmityl zeaxanthin (Kuhn, Zechmeister).<br />
It is a true " lipochrome ".<br />
The important investigations <strong>of</strong> Euler and Karrer show that carotene<br />
is very closely related to the growth-promoting vitamin-A. 2<br />
In the preparation described above we have an important means<br />
<strong>of</strong> making fi-arylacrylic acids, and from them, by hydrogenation,<br />
ft-arylpropionic acids. The method is used in the investigation <strong>of</strong><br />
alkaloids and in the synthesis <strong>of</strong> coumarin from salicylaldehyde.<br />
The methylene groups <strong>of</strong> hippuric acid and malonic acid are much<br />
more reactive than that <strong>of</strong> acetic acid. They may be caused, therefore,<br />
to condense with aldehydes under much milder conditions, e.g. by the<br />
action <strong>of</strong> pyridine. The use <strong>of</strong> malonic acid forms an extension <strong>of</strong><br />
Perkin's reaction to the aliphatic series (Doebner), e.g.<br />
/COOH<br />
CH3.CHO + CH2.(COOH)2 —> CH3.CH=C<<br />
XJOOH<br />
—> CH3.CH=CH.COOH + CO2.<br />
Crotonic Acid<br />
Cinnamic acid exists in two different configurations, as cis and<br />
trans isomerides. Ordinary cinnamic acid has the trans-form (fumaric<br />
1 Helv. Chim. Ada, 1928, 11, 87.<br />
2 See Moore, Biochem. J., 1929, 23, 803 ; Javillier, Bull. Soc. Chim., 1930, 47,<br />
489.
234 HYDKOCINNAMIC ACID. SODIUM AMALGAM<br />
acid); cis-cinnamic acid is called aHo-cinnamic acid, and was first<br />
found, along with its isomer, in the vegetable kingdom. Synthetically,<br />
it is obtained from phenylpropiolic acid C6HS.C s C.COOH by partial<br />
catalytic hydrogenation (Paal). Phenylpropiolic acid can be obtained<br />
from the dibromide <strong>of</strong> cinnamic acid by the elimination <strong>of</strong> two molecules<br />
<strong>of</strong> HBr. Two other cinnamic acids, melting at 42° and 58° respectively,<br />
are regarded as crystallographically different polymorphs <strong>of</strong><br />
aHo-cinnamic acid (Biilmann).<br />
Experiment. Hydrogenation <strong>of</strong> Cinnamic Acid.—In a glassstoppered<br />
bottle (capacity 250 c.c.) 10 g. <strong>of</strong> cinnamic acid are dissolved<br />
by shaking with about 100 c.c. <strong>of</strong> dilute sodium hydroxide<br />
solution, which is added little by little until the reaction, when<br />
tested with phenolphthalein paper—spot test with drops <strong>of</strong> the two<br />
solutions on filter paper-—is just alkaline. Two per cent sodium<br />
amalgam (freshly prepared as described below) is then added in small<br />
portions with continual shaking and frequent removal <strong>of</strong> the stopper.<br />
Altogether about 250 g. <strong>of</strong> amalgam are used. To complete the<br />
reaction the mixture is warmed on the water bath (placed in warm<br />
water, which is then heated) until all the mercury has separated in<br />
liquid form. After the liquid has cooled, the metal is separated in a<br />
funnel and the aqueous layer is acidified with hydrochloric acid.<br />
Hydrocinnamic acid is precipitated, at first in the form <strong>of</strong> an oil,<br />
which solidifies on cooling and rubbing. It is collected at the pump<br />
and crystallised from hot water containing some hydrochloric acid.<br />
Because <strong>of</strong> the low melting point <strong>of</strong> the acid (47°) the solution must<br />
be allowed to cool slowly. Compare pp. 6, 7. Yield 8 g.<br />
A sample <strong>of</strong> the material, dissolved in a little dilute sodium carbonate<br />
solution, should not decolorise a drop <strong>of</strong> permanganate<br />
solution.<br />
Cinnamic acid may also be hydrogenated catalytically (p. 377).<br />
If the sodium amalgam method is chosen, the catalytic method<br />
should be practised with phenol.<br />
Sodium Amalgam.—Mercury and sodium react with violence,<br />
sparks and flames being produced; the amalgam must therefore be<br />
made inside a fume chamber and goggles must be worn. In a mortar<br />
<strong>of</strong> moderate size 300 g. <strong>of</strong> mercury are warmed to 30°-40° and the<br />
sodium (6-5 g. in all), cut into small cubes, is introduced on the point<br />
<strong>of</strong> a glass rod about 30 cm. long ; the pieces are pushed under the<br />
surface <strong>of</strong> the liquid in rapid succession. A porous plate is used as<br />
a cover for the mortar in order to provide protection against spurt-
SALICYLALDBHYDB 235<br />
ing. While still warm the solidified amalgam is broken into small<br />
pieces and is kept in a well-stoppered bottle.<br />
Large amounts <strong>of</strong> sodium amalgam are best prepared in a<br />
fire-clay crucible ; larger pieces <strong>of</strong> sodium are fixed on the tip <strong>of</strong> a<br />
long, heavy glass rod and allowed to slide by gravity into the mercury.<br />
In order to obtain an amalgam <strong>of</strong> more than 3 per cent the<br />
crucible must be heated with a flame.<br />
a/J-Unsaturated carbonyl compounds (aldehydes, ketones, esters,<br />
and acids) can be hydrogenated by means <strong>of</strong> the usual reducing agents<br />
such as zinc and acid, sodium amalgam, sodium and alcohol, whilst the<br />
carbon-carbon double bond <strong>of</strong> defines can only be saturated by hydrogen,<br />
when activated by a catalyst. According to Thiele, the explanation<br />
<strong>of</strong> this fact is provided by assuming a 1 : 4-addition for which the<br />
doubly bound oxygen <strong>of</strong>Eers a suitable point <strong>of</strong> attack to the hydrogen :<br />
\ II r \ H l l i \ H H I<br />
>C=C—C=0 _^. >C— C=C—OH > >C—C—C=0.<br />
/ 1 2 3 4 [_/ J / |<br />
The double bonds <strong>of</strong> the benzene ring also enter, in this way, into a<br />
relationship <strong>of</strong> conjugation with carboxyl groups which are directly<br />
united to the ring. Benzole acid and the fhthalic acids are hydrogenated<br />
by sodium in alcohol (Baeyer). But hydrocarbons <strong>of</strong> the styrene type<br />
also can be hydrogenated by the same reducing agent (Klages) e.g.<br />
C6H5.CH=CH—CH3 2H > C6H5.CH2.CH2.CH3 .<br />
9. THE REIMER-TIEMANN SYNTHESIS<br />
SALIOYLALDEHYDE FROM PHENOL AND CHLOROFORM 1<br />
In a round-bottomed flask (capacity 1 1.) sodium hydroxide<br />
(80 g.) is dissolved by heating in water (80 c.c), pure phenol (25 g.)<br />
is added to the hot solution, and the mixture is cooled to 60°-65°<br />
by dipping the flask in cold water, without shaking, however, so that<br />
separation <strong>of</strong> crystalline sodium phenoxide is avoided. By means<br />
<strong>of</strong> a two-holed cork the flask is then fitted with an efficient reflux<br />
condenser and a thermometer, the bulb <strong>of</strong> which dips into the liquid.<br />
Chlor<strong>of</strong>orm (20 g.) is next poured in through the condenser, and the<br />
contents <strong>of</strong> the flask are gently shaken ; a transient fuchsine-red<br />
colour is developed in the liquid. After a period <strong>of</strong> about ten<br />
minutes, during which the temperature <strong>of</strong> the mixture is maintained<br />
1 Ber., 1876, 9, 423, 824; 1877, 10, 1562 ; 1882, 15, 2685, etc.
236 THE KBIMBK-TIBMANN SYNTHESIS<br />
between 65° and 70° by dipping the flask in cold or hot water, a<br />
second 20 g. portion <strong>of</strong> chlor<strong>of</strong>orm is added and once again, after an<br />
interval <strong>of</strong> fifteen minutes, a third portion <strong>of</strong> 20 g. At this stage<br />
the flask should frequently be shaken. To complete the reaction<br />
the flask is heated on the water bath for one hour and steam is then<br />
blown through the reaction product until chlor<strong>of</strong>orm ceases to pass<br />
over. The reaction mixture is now allowed to cool somewhat, and<br />
dilute sulphuric acid is carefully added until the orange-coloured<br />
alkaline liquid becomes acid and almost colourless. Steam is then<br />
passed through again until no more drops <strong>of</strong> oil come over with the<br />
water.<br />
The distillate is at once extracted with ether and the extract,<br />
after having been separated from the water, is heated on the water<br />
bath until most <strong>of</strong> the ether has distilled. The residue, which contains<br />
unchanged phenol as well as the salicylaldehyde, is now vigorously<br />
shaken in a small glass-stoppered bottle with two volumes <strong>of</strong><br />
concentrated commercial sodium bisulphite solution. A thick paste<br />
<strong>of</strong> the bisulphite compound <strong>of</strong> the aldehyde is formed. After this<br />
paste has stood for from half an hour to one hour the bisulphite compound<br />
is separated by filtration at the pump, pressed well on the<br />
filter funnel, and washed several times, first with alcohol and<br />
finally with ether, until completely free from adherent phenol. The<br />
crystals (small plates, iridescent like mother-<strong>of</strong>-pearl) are then decomposed<br />
with dilute sulphuric acid in a small round-bottomed flask<br />
whic,h is fitted with an air condenser and gently warmed on the<br />
water bath. After the liquid thus produced has cooled, the aldehyde<br />
which separates is extracted with ether and the ethereal solution<br />
is dried with anhydrous sodium sulphate. The pure aldehyde<br />
which remains when the ether is evaporated distils at 196°. The<br />
yield amounts to 10-12 g.<br />
From the residue after the steam distillation, filtered while hot<br />
and saturated with sodium chloride, ^-hydroxybenzaldehyde, which<br />
is not volatile with steam, crystallises, <strong>of</strong>ten only after long standing.<br />
If the filtrate, obtained when the crystalline material is separated<br />
by filtration, be extracted with ether, a further amount <strong>of</strong> the pcompound<br />
is obtained. By recrystallisation from water, to which<br />
some aqueous sulphurous acid is added, both portions can be purified<br />
together. Melting point 116°. Yield 2-3 g.<br />
If the sodium phenoxide separates at the beginning, the synthesis<br />
fails.
MECHANISM OF THE SYNTHESIS 237<br />
This reaction, which can also be used with substituted phenols,<br />
can be applied generally, but, because <strong>of</strong> side-reactions which accompany<br />
it, it is usually rather unpr<strong>of</strong>itable. Its result very distinctly<br />
recalls that <strong>of</strong> Kolbe's salicylic acid synthesis (Chap. VI. 4, p. 249), and<br />
we might be tempted to picture its course as proceeding in the same way<br />
as has been demonstrated experimentally for Kolbe's synthesis, namely,<br />
by way <strong>of</strong> a double decomposition with elimination <strong>of</strong> a molecule <strong>of</strong><br />
NaCl; part <strong>of</strong> the chlor<strong>of</strong>orm molecule would thus become attached to<br />
the oxygen <strong>of</strong> the phenol, the two remaining chlorine atoms would<br />
then be replaced by oxygen, and finally, in the phenyl formate so produced,<br />
a rearrangement involving the wandering <strong>of</strong> the formyl group<br />
(to the o- or y-position) would take place. This wandering corresponds<br />
to that which occurs in phenyl carbonate :<br />
/\—ONa + CLCClg ^ /N—O.CClg<br />
I J . H 'N. J H<br />
NaOH<br />
More probably, however, the process consists first in an addition <strong>of</strong><br />
chlor<strong>of</strong>orm to one <strong>of</strong> the double bonds <strong>of</strong> the ring and then in a change<br />
which is readily understood from the following formulae.:<br />
ONa<br />
•> I I ^ •> I I /H •><br />
The isolation <strong>of</strong> addition compounds which can only have been<br />
formed in such a way (in the cases <strong>of</strong> o- and p-cresoZ; Auwers, Ber.,<br />
1902, 35, 4207) gives decisive support to this view.<br />
As will be seen, the primary product from o-cresol cannot reconstitute<br />
the aromatic ring because <strong>of</strong> the CH3-group. Hence only NaCl<br />
is eliminated. The other two chlorine atoms are not hydrolytically<br />
removed and a quinol-like substance is formed, as the formula indicates:<br />
In the case <strong>of</strong> y-cresol the addition <strong>of</strong> chlor<strong>of</strong>orm takes place in the<br />
1 : 4-positions:<br />
HO
238 KBACTIONS OF SALICYLALDBHYDB<br />
NaO<br />
!HC12 CH3 CHC12<br />
This reaction constitutes an important pro<strong>of</strong> <strong>of</strong> the fact that in the<br />
benzene ring additions in the 1 : 4-positions occur and, at the least,<br />
it provides a valuable indication that the ^-substitution, which so <strong>of</strong>ten<br />
accompanies o-substitution, is likewise preceded by 1 : 4-addition (cf.<br />
in this connexion p. 113).<br />
Experiment,—A few drops <strong>of</strong> salicylaldehyde are dissolved in<br />
sodium hydroxide solution; an intensely yellow sodium salt is<br />
formed.<br />
A drop <strong>of</strong> ferric chloride solution produces an intense violet<br />
colour in an aqueous or alcoholic solution <strong>of</strong> the aldehyde.<br />
In salicylaldehyde the phenolic odour predominates. The aldehyde<br />
is much less liable to autoxidation than is benzaldehyde.<br />
With regard to this point compare the two aldehydes by exposing<br />
a few drops <strong>of</strong> each to the air on a watch-glass.<br />
Guaiacol, by the action <strong>of</strong> chlor<strong>of</strong>orm and alkali, gives vanillin in<br />
poor yield along with the o-aldehyde.<br />
From salicylaldehyde and sodium acetate by Perkin's synthesis<br />
coumarin is formed. (Formulate !)
CHAPTBK VI<br />
PHENOLS AND ENOL8. KETO-ENOLTAUTOMEEI8M<br />
1. CONVERSION OF A SULPHONIC ACID INTO A PHENOL<br />
/3-NAPHTHOL 1<br />
MATERIALS required: 70 g. (0-3 mole) <strong>of</strong> sodium naphthalene-<br />
/3-sulphonate, 2 210 g. <strong>of</strong> sodium hydroxide, 20 c.c. <strong>of</strong> water.<br />
The sodium hydroxide is powdered and, along with the water, is<br />
heated with stirring in a copper or nickel crucible to 280°. The<br />
thermometer, which is at the same time the stirrer, is enclosed in a<br />
copper or nickel tube about 16 cm. long and 0'8 cm. wide.<br />
The bulb <strong>of</strong> the thermometer, which is maintained in<br />
position by a bored cork, dips into a layer <strong>of</strong> oil 1 cm.<br />
thick. (See Fig. 55.) Goggles and gloves must be worn. As<br />
soon as the temperature has reached 280° the sodium<br />
naphthalenesulphonate is added rather rapidly with stirring<br />
; heating is continued with a somewhat smaller flame<br />
and the temperature is maintained between 260° and 280°.<br />
After all the salt has been added, the flame is raised<br />
somewhat, causing the molten material to become more<br />
viscous as steam is evolved and bubbles are formed.<br />
Finally, at 310°, the reaction proper sets in. After the<br />
temperature has been kept at 310°-320° for about five minutes<br />
the material becomes more mobile and the reaction is over.<br />
The molten material is at once poured in a thin layer on to<br />
a thick copper plate the edges <strong>of</strong> which have been bent slightly<br />
upwards. The dark-coloured upper layer consists <strong>of</strong> the sodium<br />
salt <strong>of</strong> naphthol. After it has cooled, the material is powdered<br />
and dissolved in water, the naphthol is precipitated from the solution<br />
with concentrated hydrochloric acid, and, after cooling, is extracted<br />
1 E. Fischer, Anleitung zur Darstellung orgamseher Praparate, 9th ed., Braunschweig,<br />
1920. Zeitschnft fur Chemie, 1867, 10, 299.<br />
2 Or the equivalent weight <strong>of</strong> naphthalene-/3-sulphomc acid, prepared according<br />
to O. N. Witt. See p. 195.<br />
239
240 SULPHONIC ACID INTO PHENOL<br />
with ether. After the ethereal solution has been dried with anhydrous<br />
sodium sulphate, the ether is removed and, finally, the naphthol<br />
which remains is distilled in a sausage flask. Boiling point 286°.<br />
Melting point 123°. Yield 30-35 g.<br />
The reaction just described is carried out technically on a large<br />
scale in iron vessels provided with stirrers, for j8-naphthol, as well as<br />
the numerous sulphonic acids which can be obtained from it by the<br />
action <strong>of</strong> sulphuric acid, is widely used for the preparation <strong>of</strong> azo-dyes.<br />
Moreover, by the action <strong>of</strong> ammonia under pressure, j8-naphthylamine<br />
is produced from j8-naphthol:<br />
C10H7.OH + NH3 = C10H7.NH2 + H2O .<br />
j8-Naphthylamine and also its sulphonic acids are likewise employed<br />
technically for the manufacture <strong>of</strong> azo-dyes. In the same way a-naphthol<br />
is made from naphthalene-a-sulphonic acid by fusion with sodium<br />
hydroxide although on a smaller scale than j8-naphthol. a-Naphthylamine,<br />
on the other hand, is obtained by the reduction <strong>of</strong> a-nitronaphthalene<br />
(analogy to aniline). The fusion <strong>of</strong> alkali salts <strong>of</strong> arylsulphonic<br />
acids with alkali also serves technically for the production <strong>of</strong> pure<br />
phenol and <strong>of</strong> many phenol derivatives.<br />
Because <strong>of</strong> the fact that the halogen is so very firmly attached to the<br />
benzene ring, the hydrolysis <strong>of</strong> chlorobenzene, a cheap substance, can<br />
only be carried out according to the following equation at very high<br />
temperatures and then with dilute solutions <strong>of</strong> alkali hydroxide (K.<br />
H. Meyer and F. Bergius).<br />
Cl + 2 NaOH —> / \ 0 N a + NaCl + H2O .<br />
The hydrolysis proceeds much more easily when the halogen is mobilised<br />
by an o- or y-nitro-group. This question has already been discussed<br />
on p. 106.<br />
A general method leads from the primary aromatic amines by way<br />
<strong>of</strong> the diazonium salts to the phenols (p. 282).<br />
By their properties and reactions the phenols are very clearly distinguished<br />
from the ordinary alcohols <strong>of</strong> the aliphatic series. The<br />
fundamental difference between the two classes <strong>of</strong> compounds is that<br />
the OH-group <strong>of</strong> the phenols is attached to a doubly bound C-atom.<br />
The phenols, therefore, behave like the similarly constituted enols, as<br />
may be deduced from the following formulae:<br />
H H H H<br />
O R \ c = c/ R ' A H O H .<br />
H OH H OH H26<br />
Phenol Enol
PHENOLS AND BNOLS 241<br />
Simple ketones such as acetone and the like are not capable <strong>of</strong><br />
existing in the " tautomeric " form H2C=C—CH3. Whence comes it<br />
OH<br />
that an arrangement such as that shown in formula A does not obtain in<br />
phenol ? The reasons are doubtless the same as those which, in general,<br />
make a rearrangement <strong>of</strong> partially (in this case doubly) hydrogenated<br />
derivatives <strong>of</strong> benzene impossible. Reference to these reasons has<br />
already been made on several occasions (e.g. p. 178). The tendency to<br />
preserve the most saturated system <strong>of</strong> the aromatic ring, with its three<br />
double bonds, determines the formation <strong>of</strong> the stable arrangement<br />
containing the hydroxyl group and hence the peculiar character <strong>of</strong><br />
phenols.<br />
The phenols are acidic because the OH-group, as in the carboxylic<br />
acids, is attached to a doubly-bound atom.<br />
—C—OH —C—OH<br />
II and II<br />
0 C<br />
It is true that the acid character <strong>of</strong> phenol itself is not very pronounced,<br />
but the acidity increases as negative substituents such as<br />
N02 and halogen are introduced into the ring. The alkali salts <strong>of</strong><br />
phenol are to a great extent hydrolysed in aqueous solution and they<br />
are completely decomposed by carbonic acid. Phenols and carboxylic<br />
acids can hence be separated by the action <strong>of</strong> carbon dioxide.<br />
Experiment.-—Carbon dioxide is passed into a moderately concentrated<br />
solution <strong>of</strong> /3-naphthol in sodium hydroxide solution until<br />
the free naphthol is precipitated.<br />
In other reactions also the OH-group <strong>of</strong> the phenols shows itself<br />
to be more reactive than that <strong>of</strong> the aliphatic alcohols. Phenols, but<br />
not alcohols, react easily with diazomethane. With other alkylating<br />
agents also, such as alkyl halides, and dialkyl sulphates, the phenols<br />
react even in aqueous alkaline solution whilst the alcohols do not react<br />
under such conditions. Benzoyl derivatives, most <strong>of</strong> which crystallise<br />
readily, are excellently adapted for the characterisation <strong>of</strong> phenols<br />
(Schotten-Baumann reaction).<br />
Experiment.—In a test tube a small amount <strong>of</strong> crystallised<br />
phenol (0-5 g.) is dissolved in 5 c.c. <strong>of</strong> water, benzoyl chloride (0-5 c.c.)<br />
is added, and the mixture, after being made distinctly alkaline with<br />
concentrated sodium hydroxide solution, is gently warmed for a short<br />
time, with shaking, over a flame. If the reaction mixture is cooled<br />
under the tap with shaking and rubbing with a glass rod, the oil
242 KBACTIONS OF PHENOLS<br />
which separates solidifies to colourless crystals, which are filtered<br />
with suction, washed copiously with water, pressed on a porous plate,<br />
and recrystallised in a small test tube from a little alcohol. Melting<br />
point <strong>of</strong> the phenyl benzoate 68°-69°.<br />
The experiment can be carried out in the same way with (3naphthol.<br />
Melting point <strong>of</strong> the benzoyl-compound 107°.<br />
The necessary remarks on the importance <strong>of</strong> this much used reaction,<br />
which can also be applied to the amines, have already been made<br />
on pp. 124,125.<br />
The nafhihols are in many respects still more reactive than phenol.<br />
This is shown most distinctly by the fact that the naphthyl ethers can<br />
be obtained by the method used for the preparation <strong>of</strong> esters <strong>of</strong> carboxylic<br />
acids, namely, directly by the action <strong>of</strong> hydrogen chloride on the phenol<br />
in the presence <strong>of</strong> the alcohol. The naphthols, moreover, react readily<br />
with zinc-ammonium chloride and with ammonium sulphite and ammonia<br />
to yield naphthylamines. The second <strong>of</strong> these two methods is a<br />
general one. It was investigated by H. Bucherer.<br />
From all these facts it can be deduced that the phenols are much<br />
more closely related to the carboxylic acids than to the alcohols <strong>of</strong> the<br />
aliphatic series.<br />
The influence <strong>of</strong> the OH-group on the reactivity <strong>of</strong> the benzene ring<br />
is <strong>of</strong> great importance. All substitution processes which are traced<br />
back to preliminary addition reactions take place much more easily<br />
with the phenols than with the hydrocarbons; as far as possible the<br />
groups which enter occupy the o- and y-positions. A number <strong>of</strong> reactions<br />
illustrating this statement is discussed below and in subsequent<br />
parts <strong>of</strong> this book. It may be mentioned here that by the<br />
action <strong>of</strong> bromine water, o-o--p-tnbromophenol is at once precipitated<br />
from an aqueous solution <strong>of</strong> phenol. (Method for the quantitative<br />
determination <strong>of</strong> phenol.)<br />
Experiment.—To an approximately 2 per cent phenol solution<br />
bromine water is added until the bromine ceases to be consumed.<br />
The colourless flocculent precipitate is separated at the pump and,<br />
after drying, is recrystallised from ligroin or dilute alcohol. Melting<br />
point 95°.<br />
According to K. H. Meyer, this surprising reactivity—which is also<br />
encountered amongst the enols—is explained by the fact that the OHgroup<br />
" activates " the double bond adjacent to it and the two neighbouring<br />
double bonds <strong>of</strong> the conjugated system (Thiele's theory) are<br />
also involved in this activation. Phenol, therefore, can yield 1 : 2- and<br />
1 : 4-substitution products with bromine, addition reactions first taking<br />
place:
OH<br />
BKOMINATION OF PHENOL 243<br />
HOBr<br />
The substitution <strong>of</strong> the second and third bromine molecules proceeds<br />
in the same way until the three favoured positions (o-, o-, and p-) are<br />
occupied by bromine. If now a fourth molecule <strong>of</strong> bromine is allowed<br />
to act on the tribromo-derivative, this molecule is attached at the<br />
1 : 4-positions in fundamentally the same way as that assumed here :<br />
OH<br />
In this case, however, the elimination <strong>of</strong> HBr can no longer lead to<br />
the production <strong>of</strong> a true benzene derivative. Actually the so-called<br />
" tribromophenol bromide ", the final product <strong>of</strong> the above reaction, is<br />
the ketobromide <strong>of</strong> a quinone and hence a derivative <strong>of</strong> dihydrobenzene.<br />
The technical uses <strong>of</strong> phenol are important, particularly in the manufacture<br />
<strong>of</strong> salicylic acid (Chap. VI. 4, p. 249), and in that <strong>of</strong> the valuable<br />
synthetic resins <strong>of</strong> the " bakelite " type (condensation with formaldehyde).<br />
Under mild conditions phenol may be caused to combine with<br />
formaldehyde giving -p-hydroxybenzyl alcohol:<br />
+ OCH,—<br />
3H2OH<br />
This alcohol, when warmed, loses water and polymerises.<br />
The direct introduction <strong>of</strong> mercury into the benzene ring <strong>of</strong> the<br />
phenols must also be mentioned here. It is sufficient to heat with<br />
mercuric acetate (Balbiano, Pesci, Dimroth) in order to bring about this<br />
reaction.
MBTHYLATION OF PHENOLS<br />
+ Hg(O.CO.CH3)2-^ f JnfoCOCHa + CH3.COOH.<br />
2. METHYLATION OF PHENOLS 1<br />
(a) Anisole.—Phenol (19 g. ; 0-2 mole) is dissolved in 100 c.c. <strong>of</strong><br />
2iV-sodium hydroxide solution in a narrow-necked glass-stoppered<br />
bottle and about one-third <strong>of</strong> the dimethyl sulphate to be used<br />
(26 g. in all) is added in one lot. (Fume chamber.) The bottle is<br />
then vigorously shaken and methyl ation takes place with evolution<br />
<strong>of</strong> heat. After about five minutes, the second third <strong>of</strong> the sulphate<br />
is added and shaking is continued. Finally, after a short time, the<br />
remainder <strong>of</strong> the methylating agent is added. During the periods <strong>of</strong><br />
shaking the stopper <strong>of</strong> the bottle is removed from time to time.<br />
When the aqueous solution on which the resulting anisole floats is<br />
no longer acid, the contents <strong>of</strong> the bottle are poured into a small<br />
round-bottomed flask to which a reflux condenser is attached ; the<br />
bottle is afterwards washed out with 20 c.c. <strong>of</strong> sodium hydroxide<br />
solution, which is also poured into the flask. To complete the reaction<br />
and to destroy any dimethyl sulphate which may still be<br />
present, the mixture is heated on the water bath for half an hour.<br />
Thereafter, when the contents <strong>of</strong> the flask have cooled, the aqueous<br />
layer is removed and the anisole, having been dried with calcium<br />
chloride, is finally distilled. Boiling point 155°. Yield 90 per cent<br />
<strong>of</strong> the theoretical. If difficulty is encountered in separating the<br />
anisole from the aqueous liquid, the methylated phenol is extracted<br />
with ether.<br />
In an analogous way phenetole is prepared from phenol by the<br />
action <strong>of</strong> diethyl sulphate.<br />
(6) 0-Naphthyl Methyl Ether (Nerolin).-—The procedure is the<br />
same as in the case <strong>of</strong> anisole, but the stoicheiometrical ratio is altered.<br />
Melting point 72°. The substance is crystalline. For a method by<br />
which it may be completely purified see Witt, Ber., 1901, 34, 3172.<br />
The neutral esters <strong>of</strong> sulphuric acid and especially the dimethyl<br />
ester are very poisonous. All experiments in which they are used must<br />
therefore be carried out very cautiously in the fume chamber.<br />
Methylations with dimethyl sulphate are always carried out in<br />
alkaline solution. They proceed very easily in the cases <strong>of</strong> carboxylic<br />
1 XJUmann, Annalen, 1903, 327, 114; 1905, 340, 208.
BTHBKS OF PHENOLS 245<br />
acids (method for the preparation <strong>of</strong> esters) and phenols, whilst in the<br />
case <strong>of</strong> aliphatic alcohols, e.g. the sugars, the alkylation takes place only<br />
with difficulty and preferably in alcoholic solution. It should be noticed<br />
that, in accordance with the equation<br />
H3C—(X Na(X<br />
C6H5ONa + >SO2—> C6H5O.CH3 + >SO2<br />
H3C—(K H3CO/<br />
only one <strong>of</strong> the methyl groups is transferred to the phenol. The salt<br />
<strong>of</strong> the methylsulphuric acid which is first formed gives up its methyl<br />
group for the same purpose only slowly and at the boiling point. Hence<br />
in practice this second methyl group is not utilised for preparative purposes.<br />
Esters <strong>of</strong> arylsulphonic acids (e.g. <strong>of</strong> toluenesulphonic acid) are<br />
also used for the alkylation <strong>of</strong> phenols.<br />
How is dimethyl sulphate prepared ?<br />
An elegant methylating agent for phenols is furnished by diazomethane.<br />
A description <strong>of</strong> its use for this purpose is given later.<br />
The ethers <strong>of</strong> the phenols are very stable substances in which the<br />
reactivity <strong>of</strong> the benzene ring, as compared with that <strong>of</strong> the phenols<br />
themselves, is appreciably reduced. The alkyl group is very firmly<br />
attached. It cannot be removed by the action <strong>of</strong> alkalis, and by that<br />
<strong>of</strong> mineral acids only at high temperature (in sealed tubes). The most<br />
useful agent for reconverting phenolic ethers into phenols is aluminium<br />
chloride, which acts in the manner shown in the following equation :<br />
C6H5.O.CH3 + AICI3 —> C6HSOA1C12 + C1.CH3<br />
vj, 3H,0<br />
C6H5.OH + A1(OH)S + 2HC1'<br />
AUyl ethers when heated yield allyl phenols (Claisen),<br />
vO.CH2.CH=CH2 ^ /\—OH<br />
~* I J—CH2.CH = CH2'<br />
whilst enolic ethers <strong>of</strong> the type>C=C—cannot undergo such rearrangement.<br />
OR<br />
The recently discovered fission <strong>of</strong> phenolic ethers (and <strong>of</strong> aliphatic<br />
ethers) by metallic sodium is <strong>of</strong> special interest (Ziegler, Schorigin), e.g.<br />
C6H5OCH3 + 2 Na —> C6H5ONa + NaCH3 .<br />
Of the substituted phenol ethers the amino-derivatives <strong>of</strong> anisole<br />
(anisidine) and phenetole (phenetidine) may be mentioned. They are<br />
prepared from the nitrophenols by alkylation and subsequent reduction<br />
<strong>of</strong> the nitro-group.<br />
Alkaline reduction <strong>of</strong> o-nitro-anisole leads (as in the case <strong>of</strong> nitrobenzene)<br />
to the hydrazo-compound, which undergoes a benzidine trans-
246 ORTHO- AND PARA-NITROPHBNOLS<br />
formation and is converted into the diphenyl base " dianisidine ", an<br />
important intermediate for the production <strong>of</strong> blue azo-dyes (p. 187).<br />
The well-known antipyretic " phenacetine " (I) and the sweetening<br />
agent " dulcine " (II) are derivatives <strong>of</strong> y-phenetidine :<br />
H5C2O—/1\—NH.CO.CHg, H5C2O-^Il\—NH.CO.NH<br />
5C2<br />
Methylated phenols very <strong>of</strong>ten form part <strong>of</strong> the molecule <strong>of</strong> natural<br />
products, in particular, <strong>of</strong> alkaloids. In the elucidation <strong>of</strong> their constitution<br />
the quantitative determination <strong>of</strong> the methoxyl groups is <strong>of</strong><br />
great importance. This determination is carried out by the excellent<br />
method <strong>of</strong> Zeisel, in which the methyl group is removed as methyl iodide<br />
by the action <strong>of</strong> concentrated hydriodic acid. This method (directions,<br />
p. 80) should be practised with the anisole already prepared.<br />
3. ORTHO- AND PARA-NITROPHENOLS<br />
Sodium nitrate (80 g.) or potassium nitrate (95 g.) is dissolved by<br />
heat in 200 g. <strong>of</strong> water in a round-bottomed flask, and before the<br />
solution has cooled completely, 100 g. <strong>of</strong> concentrated sulphuric acid<br />
are added with stirring. The liquid is cooled to 20° and then 50 g. <strong>of</strong><br />
crystallised phenol, which has been liquefied by heating with 5 c.c. <strong>of</strong><br />
water, is added drop by drop from a tap funnel, with frequent shaking<br />
; the temperature <strong>of</strong> the reaction mixture is kept between 20°<br />
and 25°. After the reaction mixture has stood for two hours, with<br />
frequent shaking, two volumes <strong>of</strong> water are added and the oil which<br />
separates is allowed to settle. As much as possible <strong>of</strong> the aqueous<br />
layer is poured <strong>of</strong>f, and the oil, after being washed twice with water,<br />
is distilled with steam. o-Nitrophenol passes over. It is filtered<br />
at the pump from the aqueous distillate and dried on filter paper.<br />
If the material thus obtained is not pure, the steam distillation<br />
is repeated. Melting point 45°. Yield 30 g. The method <strong>of</strong> removing<br />
o-nitrophenol, which may solidify in the condenser, is given<br />
on p. 28.<br />
From the residue after the steam distillation the non-volatile<br />
^-compound is isolated at the same time, at first in the form <strong>of</strong> its<br />
sodium salt. Sodium hydroxide solution (2N) is added until the<br />
reaction to Congo paper has just disappeared, 100 c.c. more <strong>of</strong> the<br />
hydroxide solution are then poured in, and the mixture is boiled with<br />
a little animal charcoal while steam is again passed through. The<br />
solution is now filtered through a folded paper and the filtrate is
NITKOPHBNOLS 247<br />
concentrated on a ring-burner until its volume is about 100 c.c.<br />
The sodium salt should crystallise when the concentrated solution<br />
is cooled. If a test with a small sample shows that the salt will not<br />
crystallise, 30 c.c. <strong>of</strong> sodium hydroxide solution (1:1) are added to<br />
the hot solution, which is then allowed to cool slowly. The salt is<br />
filtered <strong>of</strong>f at the pump and washed with 2iV-sodium hydroxide<br />
solution. l?Tom a hot solution <strong>of</strong> the salt, by precipitation with<br />
dilute hydrochloric acid, the j>-nitrophenol is obtained as an oil which<br />
crystallises on cooling. If it is not sufficiently pure, i.e. if a sample<br />
cannot be recrystallised from hot, very dilute hydrochloric acid, it<br />
is purified by reconversion into sodium salt and reprecipitation.<br />
Melting point 114°. Yield 5-10 g.<br />
The ease with which the phenols are nitrated has already been<br />
discussed. The process is not satisfactory, however, even when dilute<br />
nitric acid is used, because resinous by-products are formed as a result<br />
<strong>of</strong> oxidation and condensation. Nitration with nitrogen peroxide in<br />
non-aqueous solvents such as benzene and petrol ether gives better<br />
results (Ber., 1921, 54, 1776).<br />
By further nitration with more concentrated acid o- and y-nitrophenols<br />
are converted into the same 2 : 4-dinitrophenol, and finally<br />
into picric add. Polynitro-derivatives <strong>of</strong> benzene, such as picric acid<br />
and trinitrotoluene, can be caused to explode by detonation with mercury<br />
fulminate or lead azide. (The formulae <strong>of</strong> these two compounds<br />
should be written.) They are endothermic, i.e. the oxygen <strong>of</strong> the<br />
nitro-group can oxidise carbon and hydrogen within the molecule<br />
and heat is liberated. This intramolecular combustion is rather considerable<br />
in the case <strong>of</strong> picric acid, which is decomposed in accordance<br />
with the equation :<br />
2 C6H3O7N3 —>- 12 CO + 2 H2O + 3 N2 + H2 .<br />
m-Nitrophenol cannot be prepared from phenol by direct nitration<br />
since the OH-group is a substituent <strong>of</strong> the first order, and therefore<br />
directs chiefly to the o- and y-positions. We are dependent on an<br />
indirect way—diazotisation <strong>of</strong> »w-nitraniline and boiling the solution <strong>of</strong><br />
the diazonium salt (p. 282).<br />
In the pure state m- and y-nitrophenols are colourless, but the o-compound,<br />
on the other hand, is yellow. The salts <strong>of</strong> all three, however,<br />
are intensely coloured, the o- and »w-compounds being orange-red and<br />
orange-yellow and the y-compound deep yellow. (Use <strong>of</strong> y-nitrophenol<br />
as an indicator.)<br />
An attempt has been made to explain the strong colours <strong>of</strong> the salts<br />
<strong>of</strong> the nitrophenols as a rearrangement involving the formation <strong>of</strong> a
248 COLOUK OF SALTS<br />
quinonoid acid form (Hantzsch's aci-type) which absorbs light strongly.<br />
OH 0<br />
NO2<br />
O:N.ONa<br />
y-Nitrophenol y-Nitrophenol sodium<br />
On various grounds, however, this explanation may be questioned.<br />
In particular it may be pointed out that »w-nitrophenol behaves like<br />
the other two isomers and hence its alkali salts must also be quinonoid<br />
in form. But w-quinones are unknown throughout the whole range <strong>of</strong><br />
the aromatic compounds. Moreover, there are numerous examples <strong>of</strong><br />
substances which undergo a deepening in colour when they form salts<br />
but cannot change to a tautomeric quinone. Thus the disodium and<br />
dipotassium salts <strong>of</strong> yellowish-brown anthraquinol are deep blood-red<br />
in colour (p. 335).<br />
OH ONa<br />
)H ONa<br />
yellowish-brown blood-red<br />
Finally,- the alkali salts <strong>of</strong> phenol itself are more deeply coloured<br />
than is phenol. This fact cannot indeed be recognised subjectively,<br />
but investigation <strong>of</strong> the absorption <strong>of</strong> ultra-violet light demonstrates<br />
it. Thus it has been found that the absorption by sodium phenoxide<br />
much more nearly approaches the subjectively visible part <strong>of</strong> the spectrum<br />
than does that <strong>of</strong> the free phenol. The difference is so considerable<br />
that it provides also a satisfactory explanation <strong>of</strong> a subjectively<br />
perceptible deepening <strong>of</strong> colour from colourless to yellow. The colour<br />
<strong>of</strong> the salts <strong>of</strong> nitrophenols is therefore ascribed to the " bathychromic "<br />
(colour-deepening) effect <strong>of</strong> salt-formation.<br />
Since nitro-groups in the o- and y-positions increase the mobility<br />
<strong>of</strong> halogens directly attached to the aromatic ring (p. 106), nitrophenols<br />
can also be obtained from chloronitrobenzenes. Thus y-chloronitrobenzene<br />
can be decomposed by alkalis in the autoclave, and 2 : 4dinitrophenol,<br />
an important intermediate product for the manufacture<br />
<strong>of</strong> sulphur dyes, is produced from the corresponding chlorobenzene by<br />
an even milder treatment.<br />
(If the sodium hydroxide is replaced by ammonia, y-nitraniline is<br />
formed.)
SALICYLIC ACID 249<br />
In trinitrochlorobenzene (picryl-chloride) the chlorine is as mobile as<br />
in an acid chloride.<br />
4. KOLBE'S SALICYLIC ACID SYNTHESIS 1<br />
In a porcelain (or preferably nickel) dish 13-5 g. <strong>of</strong> pure sodium<br />
hydroxide are dissolved in 20 c.c. <strong>of</strong> water and 31 g. (0-33 mole) <strong>of</strong><br />
crystallised phenol are gradually added with stirring. The water is<br />
then evaporated by heating the constantly stirred solution, at first<br />
on a wire gauze and finally on a naked luminous flame, which is<br />
moved constantly to and fro under the dish. As soon as the lumps<br />
<strong>of</strong> material cease to agglomerate, it is powdered rapidly in a dry<br />
mortar and the fine powder is again heated in the nickel dish with<br />
efficient stirring until a perfectly dry dust is obtained. 2 This dust is<br />
poured into a tubulated retort (capacity 200 c.c.) which is dipped as<br />
deeply as possible into an oil bath. The bath is now heated to 110°<br />
and maintained at this temperature for one hour while dry carbon<br />
dioxide is passed over the sodium phenoxide (the end <strong>of</strong> the tube<br />
which delivers the gas being 1 cm. from the surface <strong>of</strong> the phenoxide).<br />
The temperature is now gradually raised, during the course <strong>of</strong> four<br />
hours, at the rate <strong>of</strong> 20° per hour to 190°, and finally, for one or two<br />
hours longer, it is maintained at 200°. During the whole <strong>of</strong> this<br />
time a moderately strong current <strong>of</strong> carbon dioxide is passed through<br />
the retort, the contents <strong>of</strong> which are stirred several times with a glass<br />
rod. The reaction product is cooled, transferred to a large beaker,<br />
and dissolved in water (the retort is also washed out several times<br />
with water). The salicylic acid is precipitated from the solution by<br />
addition <strong>of</strong> a large volume <strong>of</strong> concentrated hydrochloric acid. After<br />
the precipitate has become crystalline by cooling in ice it is collected<br />
at the pump, washed with a little water, and dried on porous plate.<br />
If a sample <strong>of</strong> the moist material can be directly recrystallised from<br />
hot water (with addition <strong>of</strong> decolorising charcoal) the whole may be<br />
purified in this way. But even in that case distillation <strong>of</strong> the crude<br />
product in superheated steam is recommended in order to become<br />
acquainted with this method. The dry material is heated in a shortnecked<br />
flask in an oil bath at 170° and a moderately strong current <strong>of</strong><br />
steam at 170°-180° is passed through (cf. p. 28). The flask should<br />
1 J. pr. Chem., 1874, [ii.] 10, 89 ; 1883, 27, 39 ; 1885, 31, 397.<br />
2 Completely dry phenoxide is essential for the suooess <strong>of</strong> the experiment.<br />
It ia convenient to choose a time for this such that the dried salt remains over<br />
night in the dish, in a vacuum desiccator over sulphuric acid and solid potassium<br />
hydroxide, before the synthesis is started next morning.
250 KOLBB'S SYNTHESIS<br />
not be connected to the superheater until the oil bath and the steam<br />
have reached the temperature mentioned. Both the connecting<br />
tube and the condenser tube must be exceptionally wide. When the<br />
acid removed from the condenser tube is dissolved in the aqueous<br />
distillate from the receiver and the solution is cooled, the acid<br />
crystallises in long, completely colourless needles. Melting point<br />
156°. Yield 10-12 g.<br />
The first stage <strong>of</strong> Kolbe's synthesis is analogous to the well-known aliphatic<br />
synthesis <strong>of</strong> alkyl carbonates from alkoxides and carbon dioxide :<br />
H5C2.ONa + CO2 —> H5C2—0—c/ ;<br />
X)Na<br />
J)<br />
>Na.<br />
The sodium phenylcarbonate so produced then undergoes rearrangement<br />
on heating ; the carboxy-sodium group wanders to the nucleus :<br />
/\0.c/° /\<br />
A relatively small amount <strong>of</strong> the y-compound is formed at the same<br />
time. It is remarkable that when potassium phenoxide is used the<br />
y-compound is the main product.<br />
Since, in Kolbe's synthesis, as here described, the mono-sodium<br />
salicylate reacts to some extent with unchanged sodium phenoxide,<br />
producing the di-sodium salt, part <strong>of</strong> the phenol is liberated and excluded<br />
from the reaction. The reaction proceeds to completion if the<br />
sodium phenoxide is heated to about 150° for a long time, with carbon<br />
dioxide under pressure in the autoclave. This is the technical method<br />
<strong>of</strong> Schmitt.<br />
In the case <strong>of</strong> polyhydric phenols the synthesis <strong>of</strong> the carboxylic<br />
acid can be carried out even in aqueous solution.<br />
Ortho- and yaro-hydroxycarboxylic acids lose CO2 when heated to<br />
high temperatures, and the ease with which this occurs increases with<br />
the number <strong>of</strong> OH-groups. (Preparation <strong>of</strong> pyrogallol from gallic acid.)<br />
How is w-hydroxybenzoic acid prepared? Discuss the reduction<br />
<strong>of</strong> salicylic acid to pimelic acid (Einhorn).<br />
Experiment.—A few drops <strong>of</strong> ferric chloride solution are added to<br />
an aqueous solution <strong>of</strong> salicylic acid. The colour reaction characteristic<br />
<strong>of</strong> phenols is obtained.
ETHEL ACETOACETATE 251<br />
Salicylic acid is manufactured on a large scale. In the dye industry<br />
it serves for the production <strong>of</strong> valuable azo-dyes which exhibit great<br />
fastness. To some extent these dyes are applied to mordanted fibres.<br />
In addition, the acid and its derivatives are widely used in pharmacy.<br />
Being a phenolcarboxylic acid it has a powerful disinfecting action<br />
(preservative). It has further proved itself an important antirheumatic<br />
and an analgetic. The derivative in which the phenolic hydroxyl group<br />
is acetylated (aspirin) has become especially popular. The first medicament<br />
<strong>of</strong> the series was the phenyl ester <strong>of</strong> salicylic acid, salol, which is<br />
produced as a by-product in the technical process. The preparation<br />
<strong>of</strong> salicylaldehyde has been described above (p. 235).<br />
pTT /~ITT /I \<br />
The alcohol saligenin C6H4
252 ACBTYLACBTONB<br />
moderate vigour only, until all the sodium has dissolved; about<br />
three hours are required. The yield is reduced if boiling is continued<br />
too long. The process is brought to an end as soon as possible and<br />
any small residue <strong>of</strong> sodium is neglected. The warm liquid is shaken<br />
with a mixture <strong>of</strong> 70 c.c. <strong>of</strong> glacial acetic acid and 80 c.c. <strong>of</strong> water<br />
until it is just acid. An equal volume <strong>of</strong> cold saturated sodium<br />
chloride solution is then added and the lower aqueous layer is separated<br />
in a tap funnel from the upper layer, which consists <strong>of</strong> ethyl<br />
acetate and ethyl acetoacetate. The mixture <strong>of</strong> esters is shaken<br />
with a little cold saturated bicarbonate solution,which is then poured<br />
away, and the excess ethyl acetate is now removed by distillation<br />
from a flask connected to a downward condenser and fitted with a<br />
thermometer. A smoky flame is used without wire gauze. As soon<br />
as the temperature reaches 95° heating is stopped and the material<br />
which remains in the flask is distilled in a vacuum through a small<br />
water-cooled condenser (preferably) into the type <strong>of</strong> receiver shown<br />
in Fig. 16 or 17. If the pressure is below 16 mm. the flask is heated<br />
on the water bath, otherwise an oil or paraffin bath is used. After<br />
small amounts <strong>of</strong> ethyl acetate and water have passed over, the<br />
temperature soon becomes constant and the bulk <strong>of</strong> the ethyl acetoacetate<br />
distils within one degree. Boiling points at various pressures<br />
: 71°/l2-5 mm., 74°/l4 mm., 79°/18 mm., 88°/29 mm., 94°/45<br />
mm., 97°/59 mm., 100°/80 mm. The yield amounts to 55 to 60 g. <strong>of</strong><br />
ethyl acetoacetate. In the flask a substance which crystallises on<br />
cooling remains. It is dehydracetic acid. What is the formula?<br />
The various stages <strong>of</strong> the experiment should be carried out without<br />
any long interruption, because otherwise the yield suffers.<br />
6. ACETYLACETONE l<br />
Finely powdered sodamide (34 g.), 2 which is kept in a closed container,<br />
is added gradually in small portions to a mixture <strong>of</strong> 120 c.c. <strong>of</strong><br />
ethyl acetate (purified as for the preparation <strong>of</strong> ethyl acetoacetate)<br />
and 32 c.c. <strong>of</strong> dry acetone. During the addition <strong>of</strong> the sodamide the<br />
mixture is cooled in a freezing mixture. The flask is provided with<br />
a cork or rubber stopper carrying a calcium chloride tube. A<br />
vigorous evolution <strong>of</strong> ammonia at once begins. After all the soda-<br />
1 L. Claiaen, Ber., 1905, 38, 695.<br />
2 The powdering should be carried out as rapidly as possible, preferably in a<br />
metal mortar (goggles to be worn). The yield is determined by the quality <strong>of</strong> the<br />
sodamide.
ACBTYLACBTONB. BBNZOYLACBTONB 253<br />
mide has been added, the flask is allowed to stand, first in ice-water<br />
for two hours with frequent shaking, and then for twelve hours at<br />
room temperature. Ice and cold water (100 g. <strong>of</strong> each) are then successively<br />
added and, after the ethyl acetate which remains has been<br />
separated, the aqueous layer is made just acid by addition <strong>of</strong> dilute<br />
acetic acid. From the solution thus obtained the acetylacetone is<br />
precipitated as copper salt by means <strong>of</strong> saturated aqueous copper<br />
acetate solution. Finely powdered copper acetate (40 g.) is dissolved<br />
in the necessary amount <strong>of</strong> boiling water. If basic copper acetate is<br />
present, a small amount <strong>of</strong> acetic acid is added. The solution is used<br />
while still lukewarm, before the salt crystallises again.<br />
After some hours the blue-green compound <strong>of</strong> copper and acetylacetone<br />
is separated by filtration with suction, washed twice with<br />
water, transferred directly from the filter funnel to a separating<br />
funnel, and, after being covered with ether, decomposed by continuous<br />
shaking with 50 c.c. <strong>of</strong> 4iV-sulphuric acid. The ethereal<br />
solution is separated and the acid layer is extracted with ether ; the<br />
extract is then combined with the ethereal solution, which is now<br />
dried over calcium chloride. After the ether has been removed by<br />
distillation the diketone is likewise distilled. The bulk <strong>of</strong> the<br />
material passes over at 125°-140° and, on repeating the distillation,<br />
at 135°-140°. The boiling point <strong>of</strong> the completely pure substance<br />
is 139°. Yield 15-20 g.<br />
If the distillation is carried out under reduced pressure (about<br />
50 mm. reduction), a purer and also more stable product is obtained.<br />
Experiment.-—One drop <strong>of</strong> ferric chloride solution is added to a few<br />
drops <strong>of</strong> an aqueous solution <strong>of</strong> acetylacetone. The reaction characteristic<br />
<strong>of</strong> enols takes place. If now the solution is cooled in ice<br />
and dilute bromine water is rather quickly added, the red colour <strong>of</strong><br />
the iron enolate disappears for a short time and then returns rapidly.<br />
Benzoylacetone. — C6H5.CO.CH2.CO.CH3 is prepared in an<br />
analogous way from acetophenone and ethyl acetate according to<br />
the procedure <strong>of</strong> Claisen, Ber., 1905, 38, 695. The yield may be as<br />
much as 75 per cent <strong>of</strong> the theoretical. The cheaper converse<br />
method-—action <strong>of</strong> sodamide on ethyl benzoate and acetone-—also<br />
succeeds in this case, although it fails when sodium or sodium<br />
ethoxide is used as condensing agent. In general the use <strong>of</strong> sodamide<br />
is to be preferred in the synthesis <strong>of</strong> 1 : 3-diketones.
254 DIBTHYL MALONATB<br />
7. DIETHYL MALONATE<br />
Monochloroacetic acid (95 g., 1 mole) is dissolved in water in a<br />
large porcelain basin and the solution, gently warmed (to 50°), is<br />
neutralised with dry solid potassium carbonate, <strong>of</strong> which 75 g. are<br />
required. Pure, finely powdered sodium cyanide (55 g., or 70 g. <strong>of</strong><br />
potassium cyanide) is then added, and the temperature is very<br />
gradually increased by heating the dish on a sand bath or an asbestos<br />
plate while the mixture is well stirred. (The whole operation must<br />
be carried out in the fume chamber.) After the cyanoacetic acid<br />
has been formed with vigorous boiling, the reaction mixture is stirred<br />
with a thermometer while it is being concentrated on a ring-burner<br />
until the temperature <strong>of</strong> the brownish viscous mass <strong>of</strong> salt is 135°.<br />
Stirring with a spatula is continued while the material is allowed to<br />
cool, because otherwise a hard mass is formed which can hardly be<br />
powdered. The solid, rapidly and throughly broken up in a large<br />
mortar, is now transferred to a flask (capacity about 11.) fitted with a<br />
reflux condenser ; with thorough shaking there are added first 50 c.c.<br />
<strong>of</strong> absolute alcohol and then gradually a cooled mixture <strong>of</strong> 200 c.c. <strong>of</strong><br />
absolute alcohol and 150 c.c. <strong>of</strong> concentrated sulphuric acid. The<br />
pasty mass produced is heated for two hours with frequent shaking<br />
on the water bath (in the fume chamber), well cooled, and again<br />
shaken with 400 c.c. <strong>of</strong> water. Salt which does not dissolve is<br />
separated at the pump and is washed several times with ether, which<br />
is then used to extract the aqueous filtrate. This is then thoroughly<br />
extracted with two further lots <strong>of</strong> ether and the combined ether<br />
extracts are shaken with concentrated sodium carbonate solution<br />
until they are no longer acid. (In view <strong>of</strong> the initially vigorous<br />
evolution <strong>of</strong> gas which takes place, the separating funnel used is at first<br />
not closed.) The ethereal solution is dried over anhydrous sodium<br />
sulphate, the ether is removed, and the residue distilled. Boiling<br />
point 195°. Yield 90-100 g.<br />
Diethyl Ethylmalonate.—Sodium (4-6 g.) is dissolved, in a small<br />
flask fitted with an efficient reflux condenser, in 75 c.c. <strong>of</strong> absolute<br />
alcohol and to the cooled solution 33 g. <strong>of</strong> diethyl malonate are<br />
added (precipitation <strong>of</strong> diethyl sodio-malonate). To the mixture<br />
thus obtained, ethyl bromide (25 g.) or ethyl iodide (35 g.) is added in<br />
small portions with shaking and the flask is then heated on the water<br />
bath until, after one to two hours, the contents are no longer alkaline.<br />
The alcohol is removed by distillation in a vacuum from the water
DIBTHYL MALONATB 255<br />
bath at 40°-50° and the ester is extracted from the residue by shaking<br />
(twice or thrice) with ether. After the ether has been removed<br />
by distillation the crude ester is distilled. Boiling point 206°-208°.<br />
Yield about 30 g.<br />
Ethylmalonic Acid,—Diethyl ethylmalonate (19 g.) is poured in<br />
small portions, with shaking, into a small round-bottomed flask<br />
containing a cooled solution <strong>of</strong> potassium hydroxide (15 g.) in 12 c.c.<br />
<strong>of</strong> water. The flask is fitted with a reflux condenser. The emulsion<br />
which is first formed soon sets to a solid mass <strong>of</strong> ethyl potassium<br />
ethylmalonate. When this is now heated moderately on the gently<br />
boiling water bath the hydrolysis sets in with vigorous evolution<br />
<strong>of</strong> heat. Heating is continued until the layer <strong>of</strong> oil has disappeared.<br />
The flask is then allowed to cool and the-—frequently crystalline-—<br />
reaction mixture obtained is twice shaken with ether in order to<br />
remove any residual ester which may have escaped hydrolysis.<br />
(Close the flask with a rubber stopper.) The ether is simply decanted.<br />
The paste is next cooled in ice and made acid to Congo<br />
paper by addition <strong>of</strong> hydrochloric acid (26 c.c. <strong>of</strong> concentrated<br />
acid (d. 1*18) +25 c.c. <strong>of</strong> water). The acid solution is shaken<br />
five times in a separating funnel with 25 c.c. portions <strong>of</strong> ether and<br />
the ethereal solution is dried over sodium sulphate. After the<br />
ether has been removed by distillation the residue is caused to<br />
crystallise by cooling and rubbing. Ethylmalonic acid can be recrystallised<br />
from benzene (a sample should be so treated), but for<br />
the purpose <strong>of</strong> conversion into butyric acid this is not necessary.<br />
Melting point 111°. Yield 12 g.<br />
Butyric Acid from Ethylmalonic Acid,—A small distilling flask<br />
having a long side tube is fixed in an oblique position with the tube<br />
directed upwards. The ethylmalonic acid is placed in the flask,<br />
which is then corked and heated in an oil bath at 180° until, after<br />
half an hour, evolution <strong>of</strong> carbon dioxide has ceased. The residue is<br />
then distilled from the same flask in the usual way ; the butyric acid<br />
passes over between 162° and 163°. Yield 80-90 per cent <strong>of</strong> the<br />
theoretical.<br />
In an analogous way, by the action <strong>of</strong> the equivalent amount<br />
(exactly 1 mole) <strong>of</strong> benzyl chloride on diethyl sodiomalonate, diethyl<br />
benzylmalonate, and finally hydrocinnamic acid, are formed.
256 PHBNYLNITKOMBTHANB<br />
8. PHENYLNITROMETHANE 1<br />
(a) aCZ-PHENYLNITROACETONITRILE SODIUM<br />
C6.H5.C.CN<br />
II<br />
NOONa<br />
In a round-bottomed flask (capacity 0-5 1.) 8 g. <strong>of</strong> sodium are<br />
dissolved in 120 c.c. <strong>of</strong> absolute alcohol. Into the solution, which<br />
is kept cool in water (precipitation <strong>of</strong> ethoxide is not detrimental) a<br />
mixture <strong>of</strong> 36 g. <strong>of</strong> benzyl cyanide (p. 137) and 32 g. <strong>of</strong> ethyl nitrate<br />
(p. 148) is poured in small portions. The salt formulated above<br />
separates gradually in the shape <strong>of</strong> almost colourless crystals. In<br />
order to allow the reaction to proceed to completion, the flask is left<br />
for one hour without cooling, but with exclusion <strong>of</strong> moisture ; the<br />
precipitate is then collected at the pump and subsequently washed<br />
first with alcohol-ether (1:1) and then with ether alone. Yield<br />
40-45 g.<br />
With ferric chloride solution a sample <strong>of</strong> the salt, dissolved in<br />
alcohol, gives an intense olive-green colour.<br />
(6) HYDROLYSIS TO THE SODIUM SALT OF<br />
aci-PHENYLNITROMETHANE<br />
The sodium salt just prepared (about 40 g.) is heated to gentle<br />
boiling in an open round-bottomed flask on a conical air bath with<br />
600 c.c. <strong>of</strong> 2iV-sodium hydroxide solution. The concentration <strong>of</strong><br />
the solution gradually increases and large amounts <strong>of</strong> ammonia are<br />
evolved. The hydrolysis is complete when this evolution ceases.<br />
The sodium salt <strong>of</strong> the acz-phenylnitromethane, which is sparingly<br />
soluble in the excess <strong>of</strong> alkali, frequently begins to separate in<br />
crystalline form even while the solution is hot. If this occurs before<br />
the reaction has ceased, hot water is added and boiling is continued<br />
until the evolution <strong>of</strong> ammonia is complete. Then the solution is<br />
allowed to cool and, with continuous shaking and efficient ice-cooling,<br />
is acidified with about 220 c.c. <strong>of</strong> rather concentrated hydrochloric<br />
acid (110 c.c. each <strong>of</strong> concentrated acid and water). Sufficient acid<br />
must be added to produce a distinct colour change on Congo paper<br />
and to cause complete precipitation <strong>of</strong> the aa-nitro-compound which<br />
1 W. Wislicenus and A. Endres, Ber., 1902, 35, 1757.
KBTO-BNOL TAUTOMBKISM 257<br />
separates in a flocculent condition. Large volumes <strong>of</strong> carbon dioxide<br />
are evolved. In order to allow time for the sensitive act-compound<br />
to change into the stable phenylnitromethane the reaction-mixture<br />
is now left over night. Next day it is exhaustively extracted with<br />
ether and the extract, after washing with sodium carbonate solution,<br />
is evaporated without previous drying. After the ether has been<br />
removed the extracted material is distilled with steam and the distillate<br />
is again extracted with ether. The ethereal solution is dried<br />
over calcium chloride and the residue, after evaporation <strong>of</strong> the ether<br />
on the water bath, is distilled in a vacuum. The phenylnitromethane<br />
passes over as a light yellow oil at 118°-119° (16 mm.). Yield 14-18 g.,<br />
i.e. on the average, 50 per cent <strong>of</strong> the theoretical.<br />
On Keto-Enol Tautomerism<br />
In the free state and in their reactions the simple aldehydes and<br />
ketones are in general known only in the aldo- and keto-forms. Erlenmeyer<br />
suggested the rule that the isomeric enol-structure, which might<br />
be formed at first in the production <strong>of</strong> acetaldehyde from glycol, for<br />
example, should in no case be capable <strong>of</strong> existence.<br />
Oxd-2—Oiio —HO v^-tio^^^-fci-<br />
OH OH OH<br />
Chiefly as a result <strong>of</strong> the work <strong>of</strong> Claisen, this rule has been proved<br />
to be erroneous. We know now that even simple aldehydes and ketones<br />
exhibit a detectable tendency to " enolise ", by the wandering <strong>of</strong> an<br />
H-atom and the simultaneous shift <strong>of</strong> a double bond.<br />
Thus it has been possible to show that in the bromination <strong>of</strong> acetone,<br />
a process which has been found to be unimolecular, not the normal<br />
keto-form, but the tautomeric enol-form reacts. The enol-form is<br />
present, in equilibrium with the keto-form, in amount too small to be<br />
measured. As soon as this amount has reacted a further quantity is<br />
formed and the process is repeated. That the reaction is unimolecular<br />
follows from the fact that it is the rate <strong>of</strong> rearrangement (I) which<br />
is measured, whilst the reaction <strong>of</strong> the enol with bromine (II) takes<br />
place with immeasurable rapidity (Lapworth).<br />
We have, consequently, the equations :<br />
CH3.CO.CH3 —> CH3.C=CH2 _"^ CH3.CBr—CH2Br<br />
, OH • . OH<br />
I II<br />
—+ CH3.CO.CH2Br .<br />
It may be mentioned here that, if water is excluded, acetone and also<br />
s
258 MECHANISM OF ACBTOACBTATB SYNTHESIS<br />
acetaldehyde are converted by metallic sodium (with evolution <strong>of</strong><br />
hydrogen), or better by sodamide, into very reactive " enolates ", e.g.<br />
CH2=C—CH3 .<br />
ONa<br />
Now the mobility <strong>of</strong> a hydrogen atom united to a C-atom which is<br />
adjacent to the C=O-group—for the change to the enol-form such<br />
mobility is necessary—is increased if still other activating groups, which<br />
are, in general, unsaturated, are united to the same C-atom. This is<br />
the state <strong>of</strong> affairs in ethyl acetoacetate in which the group —COOR exerts<br />
such activating influence.<br />
The Mechanism <strong>of</strong> the Ethyl Acetoacetate Synthesis.—Before the<br />
tautomerism <strong>of</strong> ethyl acetoacetate is discussed we must consider the<br />
mechanism <strong>of</strong> its formation, which for decades has been the subject <strong>of</strong><br />
lively discussion and was conclusively explained only in recent years<br />
(Scheibler). It has been found that even the C=O-group <strong>of</strong> the simple<br />
carboxylic esters, although in other respects inferior in activity to<br />
the true carbonyl group, can be enolised by alkali metals. Thus ethyl<br />
acetate is converted by potassium into the potassium salt <strong>of</strong> the tautomeric<br />
enol with evolution <strong>of</strong> hydrogen :<br />
CH3.C=OR K > H2C=C—OR + H.<br />
II OK<br />
0<br />
Now such enolates have an exceptionally reactive double bond<br />
which makes them capable <strong>of</strong> taking part in all kinds <strong>of</strong> addition reactions.<br />
The ethyl acetoacetate synthesis is the most important process<br />
<strong>of</strong> this type. The enolate is able to combine with a second molecule <strong>of</strong><br />
the ester; the latter is added as the two fragments R—jC^MD and OR<br />
/OR<br />
H2C:C.OR + CH3.C.O —> CH3.CO.CH2.cA)R.<br />
ONa OR X ONa<br />
The final product <strong>of</strong> the reaction, the sodium derivative <strong>of</strong> ethyl acetoacetate,<br />
is then formed by elimination <strong>of</strong> sodium ethoxide and salt<br />
formation with the ethyl acetoacetate, rearranged in the enol-form :<br />
/OR /OR<br />
CH3.CO.CH2.C^-OR ^-OR —> CH3.CO.CH2.C< -i-RONa<br />
x<br />
ON ONa<br />
^<br />
/OR<br />
—> CH3.C=CH—C< +R0H.<br />
ONa ^0<br />
The condensation <strong>of</strong> esters with ketones proceeds in an exactly<br />
similar way; the enol-form <strong>of</strong> the ketone (in the form <strong>of</strong> a salt) is the<br />
basis <strong>of</strong> the addition, e.g.
ANALOGIES TO ACETOACETATE SYNTHESIS 259<br />
CH3.C:CH2 + C6H5.COOR —> CH3.C.CH2.CO.C6H5<br />
ONa ONa OR<br />
—> CH3—C=CH.CO.C6H5 + ROH.<br />
ONa<br />
Sodium benzoylacetone<br />
In general, esters <strong>of</strong> j8-keto-acids are formed from two molecules <strong>of</strong><br />
ester, and j8-diketones from ester and ketone. The use <strong>of</strong> formic esters<br />
leads, in both cases, to hydroxymethylene compounds :<br />
-—C=CH2 HC=O /\—C—CH2—C=O<br />
ONa OR I ' ONaOR<br />
! —CO—CH=C—ONa + ROH .<br />
H<br />
Sodium derivative <strong>of</strong> hydroxymethyleneacetophenone<br />
The tendency to enolise is exceptionally pronounced in the formyl<br />
group if it is in the j8-position.<br />
In the case <strong>of</strong> the dicarboxylic esters <strong>of</strong> adipic and pimelic acids,<br />
intramolecular condensation gives cyclic esters <strong>of</strong> j8-keto-carboxylic acids<br />
(Dieckmann):<br />
CH2<br />
CH2 CH2<br />
CH2 COOR ~ "* CH-CO +R0H -<br />
COOR<br />
Ester <strong>of</strong> adipic acid<br />
CH2<br />
COOR<br />
Ester <strong>of</strong> cyclopentanone carboxylio acid<br />
Esters <strong>of</strong> succinic acid condense to esters <strong>of</strong> succinylsuccinic acid<br />
(1 : 4-diketohexamethylene-2 : 5-dicarboxylic esters). Study Baeyer's<br />
work on the hydrogenated derivatives <strong>of</strong> benzene, based on this synthesis.<br />
It is not only the esters <strong>of</strong> organic acids which combine, in the manner<br />
<strong>of</strong> the " ethyl acetoacetate synthesis ", with the enolates <strong>of</strong> ketones and<br />
<strong>of</strong> esters; an analogous behaviour is shown by the esters <strong>of</strong> nitrous<br />
and nitric acids. The process which leads to the formation <strong>of</strong> isonitrosoand<br />
acinitro-compounds yields products fundamentally similar to those<br />
already described : just as with ethyl acetate the group CO.CH3 enters,<br />
so here, the NO- and NO2-groups are involved, and " enolise " exactly<br />
as does >C=O:
260 CONSTITUTION OF ETHYL ACBTOACBTATB<br />
E.CH<br />
I<br />
K'.CONa<br />
R'<br />
RCH.NO<br />
,ONa<br />
-OC2H6<br />
R.CH.NO2<br />
, I ONa<br />
R<br />
" b< OC2Hs<br />
R.C=NONa<br />
* I<br />
R'—CO<br />
+ C2H5OH.<br />
R.C=NOONa<br />
R'—CO<br />
Condensations with alkyl nitrites and nitrates, however, are not so<br />
generally applicable as the true ethyl acetoacetate reaction, and the<br />
possibility is not excluded that they proceed in another way; compounds<br />
with " mobile " hydrogen might first be added to the inorganic<br />
part <strong>of</strong> the ester by means <strong>of</strong> an " aldol " condensation. The fact that<br />
fluorene, which contains no " active " double bond at all, combines with<br />
ethyl nitrate (as well as with ethyl oxalate) and sodium ethoxide in the<br />
same way, yielding oei-nitr<strong>of</strong>luorene, seems to support this second theory<br />
(W. Wislicenus).<br />
0<br />
H H H HO.N.OC2H5<br />
+ 2 C,HR0H .<br />
The synthesis <strong>of</strong> the sodium salt <strong>of</strong> aci-phenylnitroacetonitrile, described<br />
above, is an example <strong>of</strong> the preparative use <strong>of</strong> this reaction. The CH2group<br />
<strong>of</strong> the benzyl cyanide becomes " reactive " as a result <strong>of</strong> the proximity<br />
<strong>of</strong> C6HS and CN. Here also it may be assumed that an aci-form<br />
C6HS.CH=C=NH is the cause <strong>of</strong> this behaviour.<br />
Constitution <strong>of</strong> the Esters <strong>of</strong> the P-Ketocarboxylic Acids and <strong>of</strong> the<br />
P-Diketones.—Ethyl acetoacetate is taken as example. It reacts like a<br />
ketone with phenylhydrazine, bisulphite, and other ketone reagents;<br />
on the other hand it shows an acid reaction, it dissolves in alkalis, and<br />
gives the colour reaction with ferric chloride characteristic <strong>of</strong> enols and<br />
also <strong>of</strong> phenols. Prom this double behaviour it was formerly concluded<br />
that it was either purely ketonic or purely enolic and that the reactions<br />
in the other form were to be attributed to a rearrangement caused<br />
by the reagents used. The true state <strong>of</strong> aflairs was first disclosed by
BKOMINATION AND BNOL CONTENT 261<br />
the quantitative investigation <strong>of</strong> the structural conditions (K. H. Meyer,<br />
L. Knorr, 1911). Ethyl acetoacetate, in the cold, takes up a limited<br />
amount <strong>of</strong> bromine, a reaction which, as was mentioned above in connexion<br />
with acetone, involves the enol form only. Under suitable conditions,<br />
therefore, the amount <strong>of</strong> enol present in ethyl acetoacetate can<br />
be quantitatively determined with a standard solution <strong>of</strong> bromine. A<br />
solution <strong>of</strong> ethyl acetoacetate so titrated consumes, after a short time,<br />
a further quantity <strong>of</strong> bromine, i.e. fresh enol has been produced in the<br />
solution. It follows from this that in a solution <strong>of</strong> ethyl acetoacetate<br />
keto- and enol-forms are present in equilibrium. Under the experimental<br />
conditions chosen for the titration with bromine this state <strong>of</strong> equilibrium<br />
is attained so slowly that the accuracy <strong>of</strong> the method is not noticeably<br />
aflected.<br />
Experiment.—About 0-5 c.c. <strong>of</strong> ethyl acetoacetate is dissolved<br />
with shaking in the necessary amount <strong>of</strong> water, a few drops <strong>of</strong> ferric<br />
chloride solution are added, and to the cold solution dilute (1 : 10)<br />
bromine water is added, drop by drop, but rather quickly from a tap<br />
funnel, until the red colour <strong>of</strong> the ferric enolate has disappeared.<br />
The enol has now been completely used up by the bromine, but since,<br />
in order to restore the equilibrium, more enol is formed, the colour<br />
reappears after a short time and can at once be destroyed again by<br />
the addition <strong>of</strong> a few drops <strong>of</strong> bromine. The procedure can be<br />
repeated until the whole <strong>of</strong> the ethyl acetoacetate is converted into<br />
ethyl bromoacetoacetate. By means <strong>of</strong> this experiment the ketoenol<br />
rearrangement can be subjectively perceived.<br />
The ratio in which the keto- and enol-forms are present at equilibrium<br />
is greatly dependent on the nature <strong>of</strong> the solvent. The following table<br />
gives figures for ethyl acetoacetate :<br />
Solvent. Percentage <strong>of</strong> Enol.<br />
Water 0-4<br />
Ethyl Alcohol . . . .12-0<br />
Glacial Acetic Acid . . .5-7<br />
Benzene . . . . .16-2<br />
Petrol Ether . . . . 46-4<br />
The following simple general formula expresses the important connexion<br />
which exists between the proportions <strong>of</strong> the tautomeric compounds<br />
at equilibrium and their solubilities in the solvent concerned<br />
(van't H<strong>of</strong>l, Dimroth) :<br />
urrb G -<br />
Ga and Gb are the concentrations and La and Lb the solubilities <strong>of</strong><br />
the isomers a and b, and G is a constant independent <strong>of</strong> the solvent.
262 DBSMOTKOPISM<br />
In the case <strong>of</strong> ethyl acetoacetate we thus deduce, by reference to the<br />
table, that in water the keto-ester should be the more soluble, and in<br />
petrol ether the enol-ester ; this is actually the case.<br />
Liquid ethyl acetoacetate consists <strong>of</strong> 92-5 percent <strong>of</strong> the keto-form<br />
and 7 -5 per cent <strong>of</strong> the enol-form. The freshly distilled substance contains<br />
considerably more enol since the enol-ester, because <strong>of</strong> its lower<br />
boiling point, distils first and then more is formed in the distillation flask.<br />
Experiment.—Ethyl acetoacetate (2-5 g.) is dissolved in 20 c.c. <strong>of</strong><br />
iV-alkali hydroxide solution, the solution is cooled in ice to 0° and<br />
20 c.c. <strong>of</strong> cooled iV-hydrochloric acid are added in one lot, with<br />
shaking. A turbid milky solution is formed which, however,<br />
becomes clear in a few seconds. The enol, which is less soluble<br />
in water than the keto-form, at first separates, but changes very<br />
rapidly and almost completely into the more soluble keto-form, as<br />
the conditions <strong>of</strong> the equilibrium in water require.<br />
K. H. Meyer's " bromine method " x makes it possible to determine<br />
the enol content in almost all solutions <strong>of</strong> tautomeric substances.<br />
It has also been possible, in various ways which cannot be detailed<br />
here, to prepare both the keto- and enol-forms <strong>of</strong> ethyl acetoacetate in<br />
the pure state (Knorr, K. H. Meyer). Their physical constants are<br />
altogether different. The refractive index, for example, is 1-4225<br />
(D10o) for the keto-form and 1-4480 for the enol-form. Prom determinations<br />
<strong>of</strong> the refractive indices <strong>of</strong> equilibrium mixtures the content<br />
<strong>of</strong> both forms can be calculated by interpolation (Knorr, 1911),<br />
and these results have been confirmed spectroscopically (Hantzach,<br />
1910).<br />
Whether or no both forms <strong>of</strong> a tautomeric substance are capable<br />
<strong>of</strong> isolation in the free state depends chiefly on the velocity <strong>of</strong> rearrangement<br />
<strong>of</strong> the more labile form. The isolation <strong>of</strong> keto- and<br />
enol-forms in a permanent crystalline state was first carried out with<br />
unsymmetrical dibenzoylacetone (Claisen, 1896) :<br />
(C6H5.CO)2:CH.CO.CH3 and (C6H5CO)2:C=C—CH3 .<br />
OH<br />
For such cases in which the two forms have been brought to light<br />
solely as a result <strong>of</strong> improved experimental methods, the term " tautomerism<br />
" has been modified to " desmotropism ". In desmotropic<br />
substances the tautomeric relations are therefore particularly clear and<br />
well defined ; numerous examples have become known, which now also<br />
include aceto-acetic ester. The case <strong>of</strong> acetylacetone is quite similar,<br />
but here the formation <strong>of</strong> the enol-form is much more favoured. The<br />
liquid substance contains up to 80 per cent <strong>of</strong> enol.<br />
1 Annalen, 1911, 380, 212.
ALIPHATIC NITKO-COMPOUNDS 263<br />
In benzoylacetylacetone the tendency to enolise is so pronounced that<br />
this substance exists as enol only. The keto-form is unknown.<br />
C6HS.CO.C=C—CH3<br />
H3C—CO OH<br />
Nor can there be any question <strong>of</strong> real tautomerism in the case <strong>of</strong><br />
phenol. In its chemical properties phenol resembles the aliphatic<br />
enols in all respects. We need only recall the agreement in the acid<br />
character, the production <strong>of</strong> colour with ferric chloride, and the reactions<br />
with halogens, nitrous acid, and aromatic diazo-compounds (coupling),<br />
caused by the " activity " <strong>of</strong> the double bond and proceeding in the<br />
same way in phenols and aliphatic enols. The " enol nature " <strong>of</strong> phenol<br />
provides valuable support for the conception <strong>of</strong> the constitution <strong>of</strong><br />
benzene as expressed in the Kekule-Thiele formula, since it is an expression<br />
<strong>of</strong> the tendency <strong>of</strong> the ring to maintain the " aromatic " state<br />
<strong>of</strong> lowest energy. In this connexion the hypothetical keto-form <strong>of</strong><br />
phenol (A)—not yet obtained—would be <strong>of</strong> interest in comparison with<br />
the aliphatic ketone (B).<br />
CO<br />
CH CH2<br />
II 1<br />
CH CH<br />
\ / CH<br />
B<br />
CO<br />
CH CH2<br />
II I<br />
CH2 CH=CH2<br />
The tautomerism <strong>of</strong> the aliphatic nitro-compounds is very closely<br />
allied to that <strong>of</strong> the ketones and aldehydes. Here also there are two<br />
forms—the neutral and the acid, or so-called oci-form (Hantzsch) :<br />
—C=O O=N=O<br />
—C—H —C—H '<br />
Ketone True nitro-compound<br />
—C—OH O=N—OH<br />
I I<br />
—c —c<br />
I I<br />
Enol aci-Nitro-compound<br />
In respect <strong>of</strong> their properties, conditions <strong>of</strong> rearrangement, and<br />
reactions, we simply refer to what was said about the keto-enol change.<br />
Here, also, the bromine method enables the points <strong>of</strong> equilibrium to be<br />
determined quantitatively. The oldest and most important example<br />
<strong>of</strong> desmotropy in nitro-compounds was found in •phenylnitromethane,
264 ^C7-PHBNYLNITK0MBTHANB<br />
which exists as a stable neutral nitro-compound (an oil) and as a labile<br />
crystalline aci'-nitro-compound (Hantzsch).<br />
C6H5.CH2.NO2 and C6HS.CH=NOOH .<br />
Experiment.—Phenylnitromethane (about 2-3 g.) is shaken in a<br />
wide test tube with 15 c.c. <strong>of</strong> 2 i\f-sodium hydroxide solution. Since<br />
it is sparingly soluble in water, the neutral nitro-compound undergoes<br />
rearrangement, i.e. dissolves quite slowly. (In alcoholic solution<br />
the salt formation proceeds very rapidly.) The process <strong>of</strong><br />
dissolution can be hastened by heating. When this is complete the<br />
solution is cooled in a small beaker and a few small pieces <strong>of</strong> ice<br />
are added, followed by 20 c.c. <strong>of</strong> 2 i\f-sulphuric acid in one lot. The<br />
free act-phenylnitromethane separates in colourless crystalline flakes<br />
which are at once separated by nitration at the pump, washed with<br />
water, and pressed on porous plate. Part <strong>of</strong> the material may be<br />
recrystallised, without delay, from light petroleum (to which a few<br />
granules <strong>of</strong> calcium chloride are added). A small sample is dissolved<br />
in a little alcohol and a drop <strong>of</strong> ferric chloride solution is added. To<br />
a second larger portion a few drops <strong>of</strong> cold alcoholic bromine solution<br />
are added with cooling ; the colour <strong>of</strong> the bromine is destroyed.<br />
The same tests, applied to the phenylnitromethane in its original<br />
condition, prepared as described above, give negative results.<br />
The remainder <strong>of</strong> the acz-nitro-compound, dissolved in alcohol, is<br />
allowed to stand over night. The solution then neither takes up<br />
bromine nor gives the colour reaction with ferric chloride. If a<br />
few particles <strong>of</strong> the substance are left exposed on a watch-glass over<br />
night they are transformed into an oil.<br />
The aoi-form <strong>of</strong> phenylnitromethane is evidently capable <strong>of</strong> transitory<br />
existence only because <strong>of</strong> its low velocity <strong>of</strong> rearrangement: it<br />
cannot exist in equilibrium.<br />
The Use <strong>of</strong> Ethyl Acetoacetate and Ethyl Malonate for<br />
Synthetic Purposes<br />
Free diethyl malonate has the constitution which corresponds to<br />
the usual formula ; there is no evidence for the existence <strong>of</strong> an enol-<br />
form ROOC—CH=C
ACBTOACBTATB AND MALONATB SYNTHESES 265<br />
In the reactions which are here discussed, ethyl sodio-acetoacetate,<br />
which may be chosen as an example for the following reactions, behaves<br />
exactly as diethyl sodio-malonate.<br />
When an alkyl halide is added to a solution <strong>of</strong> ethyl sodio-acetoacetate<br />
a derivative having the alkyl group attached to carbon is<br />
formed, not the substance which would be expected with this group<br />
united to oxygen. It must be assumed, then, that the alkyl halide is<br />
first added to the reactive double bond and that the sodium halide is<br />
afterwards eliminated ; it is not merely a case <strong>of</strong> double decomposition.<br />
CH3.C=CH—COOE —>• CH3.C CH—COOK<br />
NaO NaO Br CH3<br />
—> CH3.CO.CH.COOE<br />
I +NaBr.<br />
CH3<br />
With acid chlorides the reaction is similar.<br />
On the other hand, the action <strong>of</strong> acid chlorides on ethyl acetoacetate<br />
in pyridine leads to the formation <strong>of</strong> O-acyl-derivatives, whilst the<br />
O-alkyl-derivatives can only be obtained indirectly from the acetals<br />
(p. 140) by elimination <strong>of</strong> alcohol (Claisen).<br />
H3C.C.CH2.COOE —>• H3C.C=CH.COOE + HOCH3<br />
H3CO OCH3 OCH3<br />
•<br />
O-alkyl and O-acyl compounds do not undergo rearrangement to<br />
form C-derivatives under the conditions in which the latter are prepared,<br />
as above described (cf. p. 245). This change takes place, however,<br />
at least in the case <strong>of</strong> the O-acyl derivatives, as the result <strong>of</strong> the catalytic<br />
action <strong>of</strong> solid potassium carbonate in indifferent solvents (Claisen), e.g.<br />
H3C.C=CH.COOE —> H3C.CO.CH.COOE<br />
O.CO.CH3 CO.CH3<br />
Since, now, the simple C-alkylated or C-acylated derivatives <strong>of</strong><br />
ethyl acetoacetate and diethyl malonate are again capable <strong>of</strong> yielding<br />
enolates, a second alkylation or acylation on the same carbon atom<br />
can be carried out. In the choice <strong>of</strong> the groups to be introduced at<br />
both stages the greatest variety is possible. The synthesis can be<br />
performed with all substances which contain reactive halogen and is<br />
hence not limited to halogenated hydrocarbons and acid chlorides.<br />
If dihalogenated paraffins are chosen, the reaction can also be used for<br />
the synthesis <strong>of</strong> simple carbon rings (W. H. Perkin, jun.), e.g.<br />
/OE<br />
KOOC.CH:C< + BrCH2.CH2.CH2Br -> EOOC.CH.COOE<br />
\0Na I -i-NaBr<br />
CH2.CH2.CH2Br
266 HYDKOLYSIS TO KBTONBS AND ACIDS<br />
COOE<br />
—> KOOC.C:C< < —> EOOC—C- CH2 2<br />
I ^ONa | I + NaBr.<br />
CH2.CH2.CH2Br CH2—CH2<br />
Ester <strong>of</strong> cyclobutanedicarboxylic acid<br />
Another important advantage <strong>of</strong> the ethyl acetoacetate and diethyl<br />
malonate syntheses is that such ring-compounds may be readily broken<br />
down to simpler compounds.<br />
From the fact that malonic acid loses carbon dioxide on fusion and<br />
is converted into acetic acid, we conclude that a carbon atom has not<br />
the power <strong>of</strong> holding two carboxyl groups firmly. Now this also applies<br />
to all substituted malonic acids which can be readily obtained by hydrolysis<br />
from the esters. This constitutes a desirable simplification <strong>of</strong> the<br />
final product.<br />
Example : When isopropyl bromide is used isovaleric acid is obtainable.<br />
The product <strong>of</strong> the reaction may be still further broken down by<br />
eliminating the second carboxyl group. (Preparation <strong>of</strong> cyclobutane<br />
from the dicarboxylic ester formulated above.)<br />
In ethyl acetoacetate the methylene group is united to —CO.CH3<br />
and —COOR. Free acetoacetic acid is even much less stable than<br />
malonic acid and, on merely warming in solution, decomposes in fundamentally<br />
similar fashion, into acetbne and carbon dioxide. Since all<br />
synthetic derivatives <strong>of</strong> ethyl acetoacetate behave in the same way, so<br />
that the acetoacetic acids, obtained by hydrolysis <strong>of</strong> their esters with<br />
aqueous mineral acids, decompose spontaneously with loss <strong>of</strong> carbon<br />
dioxide when heated, numerous derivatives <strong>of</strong> acetone are made available<br />
by this synthesis, by what is called ketonic hydrolysis, e.g.<br />
H3C.C=CH.COOR + H2CC1.COOR —> H3C.CO.CH.COOR<br />
ONa CH2.COOR<br />
—y CH3.CO.CH2.CH2.COOH + CO2 + 2ROH.<br />
LaevuUnic acid<br />
Concentrated alkali hydroxide decomposes the acetoacetic acid produced<br />
by hydrolysis <strong>of</strong> the ester in a different manner. The cleavage<br />
does not take place between the carboxyl group and the rest <strong>of</strong> the<br />
molecule, but between the latter and the •—CO.CH3-group, so that<br />
two molecules <strong>of</strong> acetic acid are produced. This acidic hydrolysis<br />
introduces a new variation into the synthesis as a whole. The practical<br />
importance <strong>of</strong> this acid hydrolysis may be illustrated by the same<br />
example, the condensation product <strong>of</strong> ethyl acetoacetate with ethyl<br />
chloroacetate.
DBHYDKACBTIC ACID 267<br />
HgC.CO.CH.COOR —>- H3C.COOH + H2C.COOH<br />
I I +2R0H.<br />
CH2.COOR H2C.COOH<br />
Succinic acid<br />
Another type <strong>of</strong> synthesis in which ethyl acetoacetate is used consists<br />
in the coupling <strong>of</strong> two molecules <strong>of</strong> the ester to ethyl diacetylsuccinate<br />
by the action <strong>of</strong> iodine on the sodium compound :<br />
COOR COOR COOR<br />
CH HC CH<br />
2 || +I2—> I I +2NaI.<br />
C—ONa CO CO<br />
CH CH CH<br />
Diethyl diacetylsuccinate<br />
Here, also, as in the case <strong>of</strong> alkylation, it is found that the union<br />
takes place between carbon and carbon. Information about the interesting<br />
isomerism <strong>of</strong> the esters <strong>of</strong> diacetylsuccinic acid can be found<br />
in the literature (L. Knorr).<br />
Dehydracetic acid, which was mentioned on p. 252, is formed from<br />
ethyl acetoacetate by intermolecular condensation. On boiling with<br />
acids the lactone ring is broken and a triketocarboxylic acid is produced.<br />
This acid loses CO2 and H2O and is thus transformed into dimethylpyrone:<br />
O O<br />
H3C-C CO<br />
HC CH-COCH<br />
I<br />
o<br />
The pyrone ring is <strong>of</strong> great importance because one <strong>of</strong> its oxygen<br />
atoms exhibits very marked basic properties (Collie and Tickle).<br />
Biologically, this ring arises through transformations <strong>of</strong> sugars (Kojic<br />
acid). The oxygen atom which is in ether form behaves like trivalent<br />
nitrogen and is capable <strong>of</strong> combining with acid to give salts which, by<br />
analogy with the ammonium salts, are termed oxonium salts. This<br />
property <strong>of</strong> the oxygen atom appears in many organic compounds.<br />
Thus, solutions <strong>of</strong> ethers in concentrated sulphuric acid must be assumed<br />
to contain oxonium sulphate which is hydrolytically decomposed by<br />
water.<br />
Baeyer was able to convert the tertiary salt produced by addition<br />
<strong>of</strong> methyl iodide to dimethylpyrone by the action <strong>of</strong> ammonia into a<br />
y-methoxy-derivative <strong>of</strong> pyridine and thus to make the following the
268 OXONIUM SALTS<br />
probable formula for the pyroxonium salts :<br />
Cl<br />
O<br />
I<br />
N<br />
/ \<br />
C C-CHa<br />
HC CH<br />
A<br />
H3C-C<br />
C<br />
HC<br />
C-CH3 H3C-C<br />
+2NH3<br />
CH -H2O<br />
C-CH3<br />
+NHJ<br />
COH<br />
Pyroxonium<br />
Chloride<br />
COCH3<br />
Methiodide<br />
H V C H<br />
COCH,<br />
2 : 6-Dimethyl-4-methoxypyridine<br />
Tertiary oxonium salts derived from oenzopyranole (chromanole)<br />
occur in the anthocyanin series, the red and blue pigments <strong>of</strong> many<br />
flowers and fruits (E. Willstatter, P. Karrer, R. Robinson).<br />
HCl + H,0<br />
H OH<br />
Benzopyranole Benzopyrylium chloride<br />
The anthocyanins are glucosides <strong>of</strong> polyhydric phenols and phenol<br />
ethers having OH and phenyl as substituents in the pyran ring. These<br />
glucosides can be regarded as derived from three types <strong>of</strong> sugar-free<br />
anthocyanidins.<br />
Cl<br />
C H<br />
6H<br />
Pelargonidin chloride Cyanidin chloride<br />
Delphinidin chloride has a further OH group in the position indicated.<br />
The important relations between cyanidin, quercitin, catechin, and<br />
luteolin should be studied from the point <strong>of</strong> view <strong>of</strong> plant physiology.
CHAPTBK VII<br />
THE DIAZO-COMPOUNDS<br />
GENERAL<br />
THE most important reaction <strong>of</strong> the nitrogen-hydrogen compounds, i.e.<br />
<strong>of</strong> ammonia and all its derivatives in which hydrogen remains directly<br />
united to the nitrogen, is, doubtless, that with nitrous acid. The great<br />
variety <strong>of</strong> phenomena which this reaction exhibits should be considered,<br />
from a general point <strong>of</strong> view. Together with salt formation,<br />
which indeed takes place normally with ammonia itself and with the<br />
aliphatic amines, the reactive N=O double bond <strong>of</strong> nitrous acid is <strong>of</strong><br />
outstanding importance.<br />
The simplest form <strong>of</strong> the reaction occurs in the case <strong>of</strong> the secondary<br />
amines.<br />
Dimethylamine forms, first, dimethylammonium nitrite. When the<br />
temperature is raised, intramolecular change involving the double bond<br />
<strong>of</strong> the nitrous acid takes place, water is eliminated, and acylation, i.e.<br />
formation <strong>of</strong> nitrogamine, occurs.<br />
(CH3)2NH + HONO—> (CH3)2N^-O--N=O<br />
\H<br />
—> (CH3)2N—N—OH'—> (CH3)2N.NO + H2O .<br />
OH<br />
This reaction is completely analogous to other acylation processes,<br />
such as the formation <strong>of</strong> the acetyl derivative from dimethylamine<br />
acetate. The only difference is, that since the C=O double bond <strong>of</strong><br />
acetic acid is less reactive than the N=O double bond <strong>of</strong> nitrous acid,<br />
a higher temperature is required in the former case.<br />
(CH3)2NH + O=C—CH3<br />
OH OH<br />
—>• (CH3)aN—C—CH3 + HaO .<br />
Dimethylaeetatnide<br />
269<br />
> (CH3)2N—C—CH3
270 THE DIAZO-COMPOUNDS<br />
The great velocity <strong>of</strong> esterification <strong>of</strong> nitrous acid, exceeding that <strong>of</strong><br />
all other acids, is doubtless to be traced to the same cause (p. 147).<br />
CH3.CH2—Ov<br />
CH,.CH20H + OrN.OH > >N—OH<br />
HO/<br />
~ H '> CH3.CH2— 0—N=O .<br />
Ethyl nitrite<br />
If we apply these considerations to the behaviour <strong>of</strong> ammonia it is<br />
clear that the acyl-product which is formed on heating must decompose<br />
into nitrogen and water.<br />
H3N + OrN.OH —>- | >N—OHI > N:N + 2H2O.<br />
Fundamentally the same holds for primary aliphatic amines :<br />
OH<br />
H3C.NH2 + OrN.OH > [H3C.NH—N—OH] > [H3C.N:N0H]<br />
> N=N + H3C.0H .<br />
The second intermediate product, in brackets, is known in the<br />
form <strong>of</strong> salts; we recognise that under the conditions <strong>of</strong> its formation<br />
it must decompose into nitrogen and alcohol.<br />
The simple primary amines <strong>of</strong> the aliphatic series, then, do not form<br />
diazo-compounds because the reaction which would le%d to their formation<br />
only occurs at a temperature at which they are destroyed. The<br />
reactivity <strong>of</strong> the NH2-group can, however, be increased by a neighbouring<br />
carbonyl group. Thus we come to the case <strong>of</strong> the esters <strong>of</strong> the aamino-carbozylic<br />
acids and <strong>of</strong> the a-amino-ketones. The ethyl ester <strong>of</strong><br />
glycine can be diazotised even in the cold ; the diazo-compound which<br />
does not decompose under these conditions undergoes stabilisation by<br />
elimination <strong>of</strong> water and change into ethyl diazoacetate :<br />
ROC.CH2.NH2 + OrN.OH |-B0.C.CH2.NH rE0.C.CH2.NH --.<br />
I _ ' " || >N-0H<br />
0<br />
L 0 HO J<br />
E0.C.CH2.N-| RO.C.CH—N<br />
II II U^S- II \S-<br />
0 HONJ 0 N<br />
Ethyl diazoacetate<br />
The unexpected feature <strong>of</strong> the reaction <strong>of</strong> the primary aromatic<br />
amines with nitrous acid is that the diazo-compound, which is doubtless<br />
formed at low temperatures according to the scheme so far used,<br />
undergoes rearrangement by the acid present in the solution, and forms
DIAZOMBTHANB 271<br />
a base, the salt <strong>of</strong> which, a diazonium salt, is obtained as the product <strong>of</strong><br />
the reaction.<br />
C6H5.NH2 + O:NOH > C6H5N:NOH<br />
_J^ C6H5.N-N + H2O .<br />
Cl<br />
Here we encounter a specific property <strong>of</strong> the aromatic compounds.<br />
In the aliphatic series diazonium salts are unknown because here substances<br />
<strong>of</strong> the aniline type •—C=C— cannot exist.<br />
NH2<br />
The possibility is not excluded that the ethyl ester <strong>of</strong> glycine is so<br />
easily diazotised because <strong>of</strong> a tautomeric change :<br />
EOC—CH2 KOC=CH<br />
II I -+ I I ,<br />
0 NH2 OHNH2<br />
But even then the fundamental difference between the two series<br />
remains, viz. the lack <strong>of</strong> basic properties in the aliphatic diazo-compounds.<br />
For the present it must be considered inexplicable that an aromatic<br />
nucleus—but no alkyl group—can confer strong basic properties on the<br />
nitrogen <strong>of</strong> a diazo-group united to it. As we shall learn later (p. 355),<br />
several aromatic nuclei together have a similar efEect on a carbon atom<br />
to which they are all directly united (carbonium salts). It may be<br />
recalled that the basicity <strong>of</strong> the amines themselves is greatly reduced by<br />
the aromatic ring whilst alkyl groups increase it.<br />
For the study <strong>of</strong> the diazo-compounds we recommend the excellent<br />
work Die Diazoverbindungen, by A. Hantzsch, revised by Reddelien,<br />
Leipzig, 1921.<br />
A. ALIPHATIC DIAZO-COMPOUNDS<br />
I. DIAZOMETHANE *<br />
Nitrosomethylurea.—Dissolve 20 g. <strong>of</strong> methylamine hydrochloride<br />
(p. 152) 2 and 30 g. <strong>of</strong> potassium cyanate (p. 131) inl20 c.c. <strong>of</strong><br />
1 E. A. Werner, J.C.S., 1919, 115, 1098; F. Arndt and J. Amende, Z. angew.<br />
Chem., 1930, 43, 444.<br />
2 The following cheap procedure serves for the preparation <strong>of</strong> large amounts <strong>of</strong><br />
methylamine hydrochloride (Brochet and Gambier, Bull. Soc. chim., 1895 [iii.], 13,<br />
533). Heat together in a distilling flask attached to a downward condenser 250 g.<br />
<strong>of</strong> ammonium chloride and 570 c.c. <strong>of</strong> 35 per cent formaldehyde solution. With<br />
the thermometer in the liquid, slowly raise the temperature to 104° and maintain<br />
at this point until distillation ceases (about 4-5 hours from the start). By then<br />
100-120 g. <strong>of</strong> water and methyl alcohol will have collected in the receiver. Cool<br />
the flask, remove the ammonium chloride which separates by filtration at the pump,<br />
and evaporate the filtrate to half its volume on the water bath. Again remove<br />
ammonium chloride by filtration and concentrate the filtrate until a film <strong>of</strong> crystals<br />
forms on the surface. Cool and separate the methylamine hydrochloride by filtra-
272 DIAZOMETHANE<br />
water, heat for fifteen minutes at 60°-80°, then boil for a short time,<br />
filter and cool the solution to 0°. Add now a solution <strong>of</strong> 20 g. <strong>of</strong><br />
sodium nitrite in 40 c.c. <strong>of</strong> water previously prepared and likewise<br />
cooled. Cool the mixture in ice and drop in, with mechanical<br />
stirring, 100 c.c. <strong>of</strong> cold 25 per cent sulphuric acid. The nitrosocompound<br />
separates in crystalline flocks. When these cease to<br />
separate, filter them at the pump, wash with ice-water, dry in a<br />
vacuum desiccator and crystallise from two parts <strong>of</strong> methyl alcohol.<br />
To increase the yield, cool the solution in an ice-salt freezing mixture<br />
at -15°, allow to stand for a short time, filter at the pump and wash<br />
with ether. Light yellow crystals, melting point 124°. Yield 20 g.<br />
To -convert into diazomethane, pour into a wide-mouthed conical<br />
flask 30 c.c. <strong>of</strong> strongly cooled 40 per cent potassium hydroxide and<br />
100 c.c. <strong>of</strong> pure ether. Transfer the flask to the fume chamber and<br />
add in small portions with continual shaking 10 g. <strong>of</strong> nitrosomethylurea<br />
keeping the temperature at 0°. When the reaction has ceased<br />
(5-10 minutes), pour <strong>of</strong>f the deep yellow ethereal solution, wash the<br />
residual liquid with a little ether, and dry the ethereal solution <strong>of</strong><br />
diazomethane for about three hours with a few small pieces <strong>of</strong> potassium<br />
hydroxide. If it is not to be used at once, keep the solution in<br />
a small narrow-necked glass flask closed in the manner described for<br />
ether over sodium (p. 91, footnote). The solution can be kept for<br />
several days but undergoes steady although slow decomposition with<br />
liberation <strong>of</strong> nitrogen. Consequently the storage vessel must not be<br />
completely closed.<br />
Since nitrosomethylurea, when kept in the cold, remains undecomposed<br />
for some time, make only sufficient diazomethane for<br />
immediate utilisation as required.<br />
Diazomethane is a yellow gas, boiling point - 24°. When required<br />
for preparative purposes it is used in solution only. In the free state<br />
tion with suction. Concentrate the filtrate as much as possible and finally remove<br />
residual water in a vacuum desiccator over solid sodium hydroxide and concentrated<br />
sulphuric acid. Digest the residue with chlor<strong>of</strong>orm to remove di- and trimethylamine<br />
hydrochloride and finally filter at the pump. Yield 110-125 g.<br />
In this reaction the i^-hydroxymethyl compound first formed is reduced by<br />
excess <strong>of</strong> formaldehyde:<br />
OH<br />
H2C:O+HNH2 > H2C-NH8 > CH3 NH2 .<br />
At the same time the formaldehyde (as hydrate) is dehydrogenated yielding<br />
formic acid and CO2. If the amount <strong>of</strong> aldehyde is increased trimethylamine<br />
hydrochloride is produced in an analogous manner.
EBACTIONS OF DIAZOMBTHANB 273<br />
it is explosive. In addition to ether, the alcohols, benzene, and petrol<br />
ether may be used as indifferent solvents. Acetone also may be used<br />
for short periods.<br />
Determination <strong>of</strong> the Diazomethane Content <strong>of</strong> Solutions (according<br />
to Marshall and Acree, Ber., 1910, 43, 2324).-—An aliquot portion<br />
<strong>of</strong> the solution (about one-twentieth) diluted with absolute ether is<br />
run with shaking into an ice-cooled 0-2 N ethereal solution <strong>of</strong> benzoic<br />
acid. This latter solution, which must contain an excess <strong>of</strong> acid<br />
with respect to the diazomethane, is prepared by dissolving 1-22 g. <strong>of</strong><br />
purest benzoic acid in absolute ether in a 50 c.c. measuring flask.<br />
The presence <strong>of</strong> an excess <strong>of</strong> acid is proved by the continued evolution<br />
<strong>of</strong> nitrogen, until the last portions <strong>of</strong> diazomethane have been<br />
added, when the solution should remain colourless. The excess <strong>of</strong><br />
benzoic acid is titrated with 0-liV-sodium hydroxide solution.<br />
Conveniently prepared by the method here described, diazomethane<br />
is much used in scientific work, since it enables valuable acids and<br />
phenols to be elegantly and smoothly methylated. Alcoholic OH-groups<br />
are practically never attacked by diazomethane, nor are amines aflected.<br />
Experiments.—To an ice-cooled solution <strong>of</strong> 2-3 g. <strong>of</strong> a phenol<br />
(phenol, cresol, /3-naphthol, salicylaldehyde, quinol) in a little ether,<br />
acetone, or methyl alcohol, the diazomethane solution prepared as<br />
described above is added in small portions until evolution <strong>of</strong> gas no<br />
longer takes place and the solution is coloured faintly yellow.<br />
In coloured solutions an excess <strong>of</strong> diazomethane is recognised by<br />
pouring a few drops into a small test tube and dipping in a glass rod<br />
which has been moistened with glacial acetic acid. An immediate<br />
evolution <strong>of</strong> gas indicates the presence <strong>of</strong> diazomethane.<br />
After evaporation <strong>of</strong> the solvent the products <strong>of</strong> reaction are<br />
purified by distillation, or, if they are solid, by crystallisation. Use<br />
one <strong>of</strong> the phenols available in the laboratory and report on the<br />
nature <strong>of</strong> the methyl ether obtained. Treat carboxylic acids (jptoluic,<br />
phenylacetic, cinnamic, oxalic, terephthalic, salicylic, etc.) in<br />
the same way.<br />
Some phenols react slowly with diazomethane. In such cases the<br />
substance, mixed with more than the calculated amount <strong>of</strong> diazomethane<br />
solution, is allowed to stand for several days in a vessel provided<br />
with a capillary tube in the stopper.<br />
Diazomethane, the simplest aliphatic diazo-compound, was first<br />
prepared by von Pechmann 1 in the following way :<br />
1 Ber., 1895, 28, 855.
274 DIAZO- AND AZOMBTHANB<br />
/OC2H5 /OC2H5<br />
O=C< + H2N.CH3—^O=C<<br />
H0N0 yOC2H5<br />
> O=C<<br />
X C 1<br />
Ethyl<br />
chlor<strong>of</strong>ormate<br />
X N H C H<br />
Methylurethane<br />
.<br />
4?/<br />
V'<br />
ON-VcH3 V<br />
Nitroso-<br />
methylurethane<br />
H2C
GLYCINE BSTBK HYDKOCHLOKIDB 275<br />
The azo-compound corresponding to azobenzene, azomeihane<br />
CH3.N=N.CH3, is a colourless explosive gas (at low temperatures a<br />
pale yellow liquid) obtained by dehydrogenation <strong>of</strong> the corresponding<br />
hydrazine (hydrazomethane) (Thiele, Ber., 1909, 42, 2575).<br />
For further reactions <strong>of</strong> the aliphatic diazo-compounds see ethyl<br />
diazoacetate (below).<br />
2. ETHYL DIAZOACETATE<br />
(a) Glycine Ethyl Ester Hydrochloride, 1 H5C2OOC.CH2NH2.HCL—<br />
Chloroacetic acid (94 g.; 1 mole) dissolved in 30 c.c. <strong>of</strong> water is run,<br />
at 15°, with shaking into a litre <strong>of</strong> concentrated ammonia (d. 0-913).<br />
The flask is stoppered and left for twenty-four hours. Then the<br />
liquid is heated in a basin on a ring burner (fume chamber !) until<br />
the large excess <strong>of</strong> ammonia has evaporated and its odour is hardly<br />
perceptible. Concentrated hydrochloric acid (100 c.c.) is next added<br />
to make the solution distinctly acid to Congo paper, and heating is<br />
continued over an open flame, with continuous stirring, until a sample<br />
<strong>of</strong> the pale yellow material, which is semi-solid while hot, becomes<br />
completely hard on cooling. At this stage overheating must be<br />
avoided by lowering the flame and stirring very vigorously.<br />
While the hot mass is cooling it is thoroughly ground in a porcelain<br />
mortar, and before the subsequent esterification the water which is<br />
still present is removed by transferring the powdered mixture <strong>of</strong><br />
ammonium chloride and glycine hydrochloride to a short-necked,<br />
round-bottomed flask which is suspended in a boiling water bath and<br />
evacuated with a pump. After four hours the mass is again powdered<br />
and the heating in vacuo is continued for three hours, this time in an<br />
oil bath at 115°. The salt mixture, 2 which is now in the form <strong>of</strong> a dry<br />
dust, is at once transferred to a double-necked round-bottomed flask<br />
connected by means <strong>of</strong> ground glass connexions to a reflux condenser<br />
and a gas delivery tube (Fig. 47, p. 104) and boiled with 350 c.c. <strong>of</strong><br />
absolute alcohol, whilst a strong current <strong>of</strong> dry hydrogen chloride is<br />
passed into the boiling mixture until thick fumes escape from the<br />
condenser. (Because <strong>of</strong> the " bumping " which occurs during boiling<br />
the ring <strong>of</strong> the water bath on which the flask stands is wrapped in a<br />
towel.) The hydrogen chloride apparatus is now disconnected and<br />
boiling is continued for one hour. By filtration at the pump the<br />
ammonium chloride is separated from the hot liquid and is washed<br />
1 Hantzsch and Silberrad, Ber., 1900, 33, 70.<br />
2 A few grammes <strong>of</strong> the salt mixture are laid aside for the preparation <strong>of</strong> hippuric<br />
acid as described below.
276 AMINO-ACIDS<br />
twice with hot absolute alcohol. When the filtrate cools the<br />
hydrochloride <strong>of</strong> the glycine ester separates in crystalline form.<br />
After twelve hours the crystals are collected by nitration at the<br />
pump and are recrystallised from the smallest possible amount <strong>of</strong><br />
alcohol-—frequently some ammonium chloride remains undissolved,<br />
and hence care must be taken not to use too much alcohol. In<br />
this way the salt is obtained completely pure. Melting point 144°.<br />
The thoroughly dried crude product, <strong>of</strong> which the yield amounts<br />
to 50-60 g., can be used for the preparation <strong>of</strong> ethyl diazoacetate.<br />
The yield can be increased by concentrating the mother liquor or<br />
by adding ether.<br />
In addition to this, the simplest method <strong>of</strong> synthesising a-aminoacids<br />
(a method which is less satisfactory for the preparation <strong>of</strong> higher<br />
members <strong>of</strong> the series), there are two other processes, both starting from<br />
aldehydes. Strecker obtained the nitrile <strong>of</strong> the amino-acid, Chap. V. 7,<br />
p. 229, by addition <strong>of</strong> ammonium cyanide to the next lower aldehyde,<br />
and Erlenmeyer jun. condensed hippuric acid with the aldehyde containing<br />
two carbon atoms less than the required amino-acid.<br />
In this latter process an ajS-unsaturated a-benzoylamino-acid is<br />
formed and is converted into the a-amino-acid by hydrogenation and<br />
subsequent removal <strong>of</strong> the benzoyl group by hydrolysis.<br />
R.C0 + H2C.C00H ^ R.CH=C.C00H ^ R.CH2.CH.C00H<br />
H | •* I •* |<br />
NH.COC6HS NH.COC6HS NH.COC6H5<br />
R.CH2.CH.C00H + C6H5.COOH<br />
y I<br />
NH2<br />
Recall the importance <strong>of</strong> the amino-acids as units from which the<br />
proteins are built up. What amino-acids have hitherto been isolated<br />
from proteins by digestion and by acid hydrolysis ?<br />
By the method <strong>of</strong> E. Fischer it is possible to carry out a separation,<br />
in some degree quantitative, <strong>of</strong> the individual a-amino-acids. They are<br />
esterified as described above, and the esters are then separated from one<br />
another by fractional distillation <strong>of</strong> the mixture in vacuo.<br />
It is supposed that in the protein molecule the individual amino-<br />
acids are united through amide linkages. For the synthesis <strong>of</strong> the so-<br />
called peptides E. Fischer condensed a molecule <strong>of</strong> the chloride <strong>of</strong> an<br />
amino-acid with a molecule <strong>of</strong> amino-acid, e.g.<br />
H2N.CH2.COC1 + H2N.CH.C00H H2N.CH2.CO.NH.CH.COOH<br />
CH3<br />
CH3<br />
Glycylalanme
HIPPUKIC ACID 277<br />
This procedure was also used in building up polypeptides <strong>of</strong> high<br />
jnolecular weight.<br />
Amino-acids in solution are quantitatively determined as follows :<br />
1. Method <strong>of</strong> van Slyke. The nitrogen, evolved when nitrite is<br />
added to an acid solution <strong>of</strong> the amino-acid, is measured.<br />
2. Sorensen's method. The amino-acid is condensed with formaldehyde<br />
and the substance produced is now a sufficiently strong acid<br />
to be titrated.<br />
3. Method <strong>of</strong> Willstatter and Waldschmidt-Leitz. Direct titration<br />
in alcoholic solution with 0-1 iV-alkali using phenolphthalein as indicator.<br />
Experiment. Hippuric Acid.—A few grammes <strong>of</strong> the mixture <strong>of</strong><br />
glycine hydrochloride and ammonium chloride just prepared are<br />
boiled with 10-14 c.c. <strong>of</strong> alcohol. The mixture is freed from the<br />
undissolved ammonium chloride by nitration and the nitrate is<br />
evaporated to dryness on the water bath (remove alcohol completely<br />
!). The residue, dissolved in a little water, is benzoylated in<br />
a small glass-stoppered bottle by the Schotten-Baumann method<br />
(p. 241). An excess (about 2-3 moles) <strong>of</strong> benzoyl chloride is gradually<br />
added in small portions, with continuous vigorous shaking, to the<br />
solution, which is kept alkaline throughout and is as concentrated as<br />
possible. When the odour <strong>of</strong> the chloride is no longer perceptible<br />
concentrated hydrochloric acid is added until the solution is acid to<br />
Congo paper. After some hours the crystalline sludge which has<br />
formed is filtered at the pump and the reaction product, when dried,<br />
is freed from benzoic acid by washing with ether. The hippuric acid<br />
is then recrystallised from hot water. Melting point 187°.<br />
Hippuric acid is a normal product <strong>of</strong> metabolism. It is produced<br />
in the kidney by the enzymic union <strong>of</strong> benzoic acid and glycine (Schmiedeberg<br />
and Bunge, 1877). In birds benzoic acid is rendered innocuous<br />
by combination with ornithine (aS-diamino-valeric acid) to form the<br />
dibenzoyl-derivative, so-called ornithuric acid (Jafle).<br />
(6) Ethyl Diazoacetate - 1 —Glycine ethyl ester hydrochloride (47 g.;<br />
0-33 mole), freed from excess <strong>of</strong> hydrochloric acid by thorough<br />
drying, is dissolved in a separating funnel (capacity 0-75 1.) in just<br />
sufficient water, ether to form a supernatant layer is poured in, and<br />
the cold saturated aqueous solution <strong>of</strong> 26 g. <strong>of</strong> commercial sodium<br />
nitrite is then run in, followed by 4 N-sulphuric acid, added drop by<br />
drop (through a dropping tube) with vigorous shaking. The ethyl<br />
1 Curtiua, J. pr. Chem., 1888, 38, 396; W. Fr&nkel, Z. physikal. Chem., 1907,<br />
60, 202.
278 ETHYL DIAZOACBTATB<br />
diazoacetate which separates as a turbidity is removed each time by<br />
shaking with supernatant ether. After 20 c.c. <strong>of</strong> the sulphuric acid<br />
have been dropped in, not too slowly, the aqueous solution is run <strong>of</strong>f,<br />
so that the ester, when it becomes concentrated, is not exposed too<br />
long to the action <strong>of</strong> the free acid. Then fresh ether is added and<br />
more sulphuric acid is dropped in. Separation <strong>of</strong> the aqueous solution<br />
and renewal <strong>of</strong> the ether are repeated five or six times.<br />
Finally, when no further turbidity is produced and the excess <strong>of</strong><br />
nitrous acid dissolves in the ether with a green colour, the addition <strong>of</strong><br />
acid is stopped and the combined ether extracts are shaken, first with<br />
FIG. 56<br />
Fumpi<br />
a little sodium carbonate solution (until a permanent red colour is<br />
obtained) and then, twice, with a little water. The ethereal solution<br />
is now dried over a little calcium chloride for about half an hour with<br />
frequent shaking, and most <strong>of</strong> the ether is removed by distillation at<br />
ordinary pressure from a 250 c.c. distilling flask (having its side tube<br />
high up in the neck) heated on a water bath, at first at a temperature<br />
not exceeding 40°. The last third <strong>of</strong> the ether, however, is<br />
distilled in vacuo at not more than 25 0 . 1 Water (20 c.c.) and solid<br />
barium hydroxide (2 g.) are added to the residue, which is then<br />
purified in the same flask by distillation in steam under reduced<br />
pressure. This distillation is carried out like an ordinary steam<br />
distillation (the apparatus is shown in Fig. 56). The steam is<br />
1 The method <strong>of</strong> purification described below yields a very pure product such<br />
as is necessary for the determination <strong>of</strong> the concentration <strong>of</strong> H--ions by the method<br />
<strong>of</strong> Bredig and Frankel (pp. 279-280). The yield, however, is somewhat smaller<br />
than when the distillation in vacuo is at once carried out at this point.
STEAM DISTILLATION IN A PAKTIAL VACUUM 279<br />
generated in a round-bottomed flask not quite half-filled with water<br />
and closed with a two-holed rubber stopper through which pass a<br />
capillary and a suitably bent delivery tube. The flow through the<br />
capillary, which should not be too narrow, can be regulated by a<br />
screw-clip. The receiver is immersed up to the neck in an efficient<br />
freezing mixture.<br />
The steam generator is now warmed to 40° in a water bath while<br />
the distillation flask is kept at 30°-35° by means <strong>of</strong> a basin <strong>of</strong> warm<br />
water. At a pressure <strong>of</strong> 20-30 mm. the ethyl diazoacetate distils<br />
with water in forty-five to sixty minutes. The contents <strong>of</strong> the receiver<br />
are thrice extracted with ether, and after the combined extracts<br />
have been dried with calcium chloride, the ether is removed by<br />
distillation, at first from a water bath at 40° and finally in vacuo.<br />
Lastly the ethyl diazoacetate is purified by distillation in a vacuum.<br />
A short condenser and a receiver cooled in a freezing mixture are<br />
used. Boiling point 45°/12 mm. Yield 20-25 g. (theoretical 38 g.).<br />
The pure product can be kept for a long time, but should not be<br />
stored in a tightly closed vessel.<br />
Ethyl diazoacetate, discovered in the year 1888 by T. Curtius, was<br />
the precursor <strong>of</strong> hydrazine and hydrazoic acid.<br />
Hydrazine was first obtained by hydrolytic decomposition <strong>of</strong> " bisdiazoacetic<br />
acid ". The latter, a tetrazine derivative, is obtained from<br />
ethyl diazoacetate in the form <strong>of</strong> alkali salt by the (catalytic) action <strong>of</strong><br />
strong alkali. Two molecules <strong>of</strong> the acid simply unite and, at the same<br />
time, the ester group is hydrolysed :<br />
y N—NH<br />
KOOC—CH J3H.C00K —>• KOOC.C^ /C.COOK<br />
^ HN—N<br />
When bis-diazoacetic acid is boiled with acid it is decomposed into<br />
hydrazine and oxalic acid. For details see Ber., 1908, 41, 3161.<br />
Ethyl hydraziacetate produced by the hydrogenation <strong>of</strong> ethyl diazoacetate<br />
is likewise hydrolysed by acid yielding hydrazine, glyoxylic<br />
acid, and alcohol. The hydraziacetate is the hydrazone <strong>of</strong> ethyl glyoxylate<br />
K00C.C=N.NH2.<br />
H<br />
Like those <strong>of</strong> all the simple aliphatic diazo-compounds the manifold<br />
reactions <strong>of</strong> ethyl diazoacetate are determined by the lability <strong>of</strong><br />
the nitrogen. The elimination <strong>of</strong> the latter is catalytically accelerated<br />
by aqueous acids, and, indeed, the velocity <strong>of</strong> decomposition is directly<br />
proportional to the hydrogen ion concentration, so that a means is<br />
provided by which this concentration can be measured for acids <strong>of</strong>
280 DIAZOACBTATB AND HYDKOGEN IONS<br />
unknown strength (Bredig, Frankel, Z. physikal. Chem., 1907, 60,<br />
202).<br />
After the nitrogen has been eliminated an unsaturated radicle<br />
ROOC.CH remains and undergoes various further changes. In the<br />
presence <strong>of</strong> water, the components <strong>of</strong> the latter are added on to give<br />
esters <strong>of</strong> hydroxyacetic acid. Addition <strong>of</strong> HC1 gives esters <strong>of</strong> chloroacetic<br />
acid, that <strong>of</strong> iodine esters <strong>of</strong> diiodoacetic acid ; carboxylic acids,<br />
alcohols, aldehydes, amines, NO2, and triphenylmethyl are added in<br />
a similar way. If, as in thermal decomposition, an addendum is lacking,<br />
two radicles unite to give fumaric esters.<br />
2ROOC.CH< —> ROOC.CH = CH.COOR.<br />
Experiments,—In order to learn, at least qualitatively, the<br />
influence <strong>of</strong> the hydrogen ion concentration on the velocity <strong>of</strong> decomposition,<br />
about 0'5 c.c. <strong>of</strong> ethyl diazoacetate is dissolved in a<br />
little 50 per cent alcohol and the solution is divided into two portions<br />
in small beakers to which respectively 1 c.c. <strong>of</strong> 0-1 iV-hydrochloric<br />
acid and 1 c.c. <strong>of</strong> 0-1 iV-acetic acid (prepared in a measuring cylinder<br />
from glacial acetic acid) are added.<br />
Further, to an ethereal solution <strong>of</strong> the ester a little ethereal<br />
solution <strong>of</strong> iodine is added. The colour <strong>of</strong> the solution does not<br />
disappear until after some time and nitrogen is evolved.<br />
In addition to the reactions mentioned, ethyl diazoacetate takes<br />
part in many condensations with acetylene and ethylene derivatives,<br />
when the nitrogen is retained in the molecule. Thus, with esters <strong>of</strong><br />
fumaric acid, for example, pyrazoline tricarboxylic esters are produced :<br />
sN CH.COOR ,N=N<br />
ROOC.CH<br />
—> ROOC.CH I<br />
IH.COOR ROOC^C—C—COOR<br />
H H<br />
The decomposition <strong>of</strong> these latter esters at high temperatures constitutes<br />
the important synthesis <strong>of</strong> cydo-propane derivatives (Btichner) :<br />
H<br />
ROOC—C—N\N<br />
ROOC—CH<br />
i / —> r \ + N ROOC—C—C—COOR<br />
H H<br />
2-<br />
ROOC—CH—CH—COOR<br />
Such derivatives occur in various stereoisomeric forms dependent on the<br />
plane <strong>of</strong> the ring.
DIAZOTISATION OF ANILINE 281<br />
Benzene reacts in the same way, at high temperature, with ethyl<br />
diazoacetate (Btichner)<br />
N \<br />
|| \CH.COOR —> | I >CH.COOR + N2<br />
Ester <strong>of</strong> mor-caradiene carboxylic acid<br />
(Psewdo-phenylacetic ester)<br />
When the cyclopropane ring <strong>of</strong> this interesting reaction product is<br />
broken as a result <strong>of</strong> isomerisation two substances may be formed :<br />
CH2.COOR<br />
' COOR —> I \ .COOR .<br />
V<br />
Phenylaoetio ester Ester <strong>of</strong> eyefo-heptatriene<br />
carboxylic acid<br />
Ethyl diazoacetate condenses with diethyl malonate to yield a<br />
derivative <strong>of</strong> 4-hydroxypyrazole (Bertho and Niissel, Annalen, 1927,<br />
457, 278) :<br />
^N—NH<br />
j + H2C(CO2C2H5)2<br />
Further details <strong>of</strong> the reactions <strong>of</strong> the aliphatic diazo-compounds<br />
are to be found in : H. Wieland, Die Hydrazine, Stuttgart, 1913, pp. 97<br />
et seq.<br />
OH<br />
B. AROMATIC DIAZO-COMPOUNDS<br />
3. DIAZOTISATION OF ANILINE. PHENOL, IODOBENZENE AND<br />
BENZENE FROM ANILINE. ISOMERISM OF THE DIAZO-COM-<br />
POUNDS<br />
(a) Preparation <strong>of</strong> a Diazonium Salt in Solution,—Concentrated<br />
sulphuric acid (30 c.c.) is poured with good stirring into 150 c.c. <strong>of</strong><br />
water in a jar or beaker (capacity 1 1.) and to the hot dilute acid<br />
30 g. <strong>of</strong> freshly distilled aniline are added. The aniline sulphate<br />
solution is now cooled in ice {not in a freezing mixture) and, after<br />
250 g. <strong>of</strong> ice have been added gradually in small portions, with the<br />
result that some <strong>of</strong> the sparingly soluble salt has been precipitated,<br />
the solution <strong>of</strong> 22 g. <strong>of</strong> sodium nitrite in 90 c.c. <strong>of</strong> water is run in<br />
gradually from a dropping funnel. During the addition <strong>of</strong> the nitrite<br />
solution the contents <strong>of</strong> the beaker are vigorously stirred. When
282 PHENOL FROM ANILINE<br />
most <strong>of</strong> the nitrite has been added a test with potassium iodidestarch<br />
paper 1 is made in order to discover whether or no an excess<br />
<strong>of</strong> nitrous acid is present. In this connexion it must be remembered<br />
that towards the end <strong>of</strong> the reaction the concentration <strong>of</strong> the reactants<br />
decreases greatly so that the diazotisation becomes slow.<br />
A few minutes must, therefore, be allowed to elapse (after the last<br />
addition <strong>of</strong> nitrite) before the test is made. When, finally, after five<br />
minutes, free nitrous acid in small amount can still be detected, the<br />
diazotisation is at an end. The aniline sulphate must, <strong>of</strong> course,<br />
have dissolved completely.<br />
A sample <strong>of</strong> the reaction mixture should not become turbid when<br />
sodium acetate solution is added. But if now a few drops <strong>of</strong> a<br />
solution <strong>of</strong> an aniline salt are poured in, there is precipitated yellow<br />
diazoaminobenzene, which can be re-dissolved with concentrated<br />
hydrochloric acid after a few small pieces <strong>of</strong> ice have been added.<br />
Further, when a few particles <strong>of</strong> j8-naphthol or <strong>of</strong> R-acid are dissolved<br />
in a small excess <strong>of</strong> 2 iV-sodium hydroxide solution and a<br />
sample <strong>of</strong> the diazo-solution is added, an intense red colour is produced.<br />
The development <strong>of</strong> this colour, which results from " coupling<br />
", is an infallible test for a diazonium salt, and hence also for<br />
the corresponding primary aromatic amine.<br />
(6) Preparation <strong>of</strong> Phenol from the Diazonium Salt Solution by<br />
Boiling.-—One third <strong>of</strong> the freshly-prepared diazonium sulphate<br />
solution is used in this experiment. The remaining two thirds are<br />
used for reactions (c) and (d). Nitrogen is slowly evolved from<br />
the solution, even on standing at room temperature. The decomposition<br />
is, however, caused to proceed at a slightly raised temperature<br />
(40°-50°), in a round-bottomed flask on a gently boiling<br />
water bath. After the evolution <strong>of</strong> gas has slackened, the resulting<br />
phenol is directly distilled with steam. When all the phenol has<br />
passed over (test a sample with bromine water !) the distillate is<br />
saturated with common salt and extracted several times with ether.<br />
The extract is dried with calcium chloride and after the usual treatment<br />
the phenol is distilled from a small flask. Boiling point 183°.<br />
Yield 6-7 g. The product should soon solidify.<br />
1 A small piece <strong>of</strong> starch the size <strong>of</strong> a pea is finely powdered, dropped, with good<br />
stirring, into 200 c.c. <strong>of</strong> boiling water and kept at the boil for a short time. After<br />
the liquid has cooled a fragment <strong>of</strong> potassium iodide as large as a lentil is dissolved<br />
in a little water and added. Long strips <strong>of</strong> filter paper about 3 cm. wide are soaked<br />
in the liquid and then dried in an acid-free atmosphere on a stretched string. After<br />
drying, the strips are cut up and kept in ft closed container.
IODOBBNZBNE FKOM ANILINE 283<br />
For preparative diazotisations it is important to use a sufficient<br />
excess <strong>of</strong> acid and to keep the temperature down. Two moles <strong>of</strong> acid<br />
are required for each mole <strong>of</strong> amine, one for salt formation and one for<br />
liberating the nitrous acid from the nitrite. As a rule 2-5-3-0 moles<br />
are used. The excess is required to prevent condensation <strong>of</strong> the<br />
diazonium salt with unchanged base to diazoamino-compound; such<br />
condensations take place in a faintly acid medium. The test for unchanged<br />
amine, accordingly, consists in buffering the free mineral acid<br />
with sodium acetate, and so providing a solution faintly acid with<br />
acetic acid, under which conditions the diazoamino-compound is formed.<br />
The latter is decomposed by mineral acids into diazonium salt and<br />
amine salt, e.g.<br />
C6H6.N=N—NH.C6H5 2HC1 > C6HS.N=N + HC1.NH2.C6HS .<br />
Cl<br />
There are, however, a few diazonium salts which couple with the<br />
parent base even in acid solution, e.g. w-phenylenediamine (Bismarck<br />
brown).<br />
In diazotisation the addition <strong>of</strong> nitrite is controlled by means <strong>of</strong><br />
potassium iodide-starch paper. When the reaction is complete the<br />
paper should become blue, but the excess <strong>of</strong> nitrite should be as small as<br />
possible. It should be remembered that diazotisation is not an ionic<br />
reaction, but requires time ; especially towards the end a few minutes<br />
must elapse before the test is made.<br />
Sparingly soluble salts <strong>of</strong> primary aromatic amines are diazotised in<br />
suspension, with vigorous stirring. Very weak bases such as halogenated<br />
anilines and nitroanilines require a large excess <strong>of</strong> acid for salt<br />
formation; they are first dissolved in just sufficient hot concentrated<br />
hydrochloric acid, which is then simultaneously cooled in ice and<br />
diluted. In this way the salts, which are mostly sparingly soluble, are<br />
precipitated in a finely divided condition. Dissolution in concentrated<br />
sulphuric acid and direct diazotisation <strong>of</strong> the sulphate, precipitated as<br />
a fine powder by means <strong>of</strong> ice, is <strong>of</strong>ten to be recommended. The free<br />
amines, however, should never be diazotised in acid suspension because<br />
they react far too slowly. Salt formation should first be ensured.<br />
The stability <strong>of</strong> the diazonium salts varies; there are some, for<br />
instance, in the anthraquinone series, which can be crystallised from<br />
hot water.<br />
(c) Iodobenzene from Aniline.—To the third <strong>of</strong> the diazonium<br />
sulphate solution (p. 282) set aside for the purpose in a roundbottomed<br />
flask (capacity 0-5 1.) a solution <strong>of</strong> 15 g. <strong>of</strong> potassium<br />
iodide in 20 c.c. <strong>of</strong> water is added, and the mixture, kept cool in<br />
water, is allowed to stand for some hours. The flask, fitted with an<br />
air condenser, is then heated on the water bath (which is kept boiling
284 PHENYL IODOCHLOKIDB<br />
moderately) until evolution <strong>of</strong> nitrogen has ceased. The contents<br />
are now made strongly alkaline with concentrated sodium hydroxide<br />
solution in order to fix the phenol formed as a by-product, and the<br />
iodobenzene is distilled with steam ; it is separated in a funnel from<br />
the aqueous portion <strong>of</strong> the distillate, dried with a few lumps <strong>of</strong><br />
calcium chloride, and finally distilled. If the separation in the<br />
funnel is sharp no ether need be used. Boiling point 189°-190°.<br />
Yield 14-16 g.<br />
It is remarkable that the aromatic iodo-compounds can be converted<br />
via addition products with chlorine into organic iodine derivatives containing<br />
multivalent iodine (V. Meyer, Willgerodt).<br />
Phenyl Iodochloride.—Iodobenzene (3 g.) is dissolved in chlor<strong>of</strong>orm<br />
(15 c.c), and chlorine from a cylinder is passed into the solution<br />
(cooled in ice) until absorption <strong>of</strong> the gas ceases. The beautiful<br />
light yellow crystals produced are collected at the pump, washed<br />
with chlor<strong>of</strong>orm, and dried in the air on filter paper.<br />
Cl<br />
The phenyl iodochloride C6HSI
IODOXYBBNZBNB 285<br />
into a test tube, gives a copious deposit <strong>of</strong> crystals. After the<br />
concentrated solution has cooled the crystalline material is collected<br />
at the pump, etc.<br />
In general the iodonium bases are formed from iodoso- and iodoxycompounds<br />
in the presence <strong>of</strong> alkali, preferably silver oxide; the two<br />
organic iodine compounds combine with elimination <strong>of</strong> iodate.<br />
0. wmT C6H6.I.C6HS<br />
C6H6.IO+ ^>I-C6H5 ^25. 5H +NaI03.<br />
Iodoxybenzene is formed, together with iodobenzene, from iodosobenzene<br />
by intermolecular dismutation :<br />
C6H6.IO + OI.C6H5 —• C6H5.l/ +C6H5I,<br />
just as nitrous acid undergoes dismutation to nitric acid and nitric oxide.<br />
This reaction takes place to a slight extent even in the cold ; hence the<br />
appearance <strong>of</strong> the iodonium base as a by-product in the preparation <strong>of</strong><br />
iodosobenzene.<br />
The iodoso- and, in particular, the iodoxy-compounds decompose<br />
with a pufE when heated, since the oxygen which they contain is present<br />
in a state <strong>of</strong> tension. They liberate an equivalent amount <strong>of</strong> iodine<br />
from acidified potassium iodide solution and are thereby reconverted<br />
into iodobenzene.<br />
The basic function <strong>of</strong> the iodine in the iodonium bases, which<br />
correspond exactly to the ammonium, sulphonium, and oxonium bases,<br />
is most interesting. A molecule <strong>of</strong> diphenyliodonium iodide has the<br />
same atoms as two molecules <strong>of</strong> iodobenzene and decomposes on heating<br />
with liberation <strong>of</strong> heat (contrast other dissociations such as those <strong>of</strong><br />
N2O4, NH4C1, PC15) into two moles <strong>of</strong> C6H5I. Test with a small sample<br />
in a tube.<br />
As is still the case to-day with the diazonium compounds, so it was<br />
for long thought that the aromatic compounds containing multivalent<br />
iodine, which were simultaneously and independently discovered by<br />
V. Meyer and by C. Willgerodt, formed a class <strong>of</strong> substances peculiar to<br />
the aromatic series. But in 1909 Thiele found analogues to all these<br />
compounds amongst the defines, with chloroiodoethylene CHC1=CHI as<br />
their simplest parent substance. Even methyl iodide, at low temperatures,<br />
can combine with chlorine, but the product decomposes again<br />
readily, yielding methyl chloride and iodine chloride (replacement <strong>of</strong><br />
iodine by chlorine). The derivatives <strong>of</strong> multivalent iodine are not<br />
stable, unless the iodine is attached to a doubly bound carbon atom.<br />
(d) Benzene from Aniline.-—An alkali stannite solution is prepared<br />
by mixing a solution <strong>of</strong> 50 g. <strong>of</strong> sodium hydroxide in 60 c.c.<br />
<strong>of</strong> water with the turbid solution <strong>of</strong> 40 g. <strong>of</strong> stannous chloride in
286 B E N Z E N E F K O M ANILINE<br />
200 c.c. <strong>of</strong> water and cooling at once; the stannite is gradually<br />
added to the last third <strong>of</strong> the diazo solution, with efficient ice cool-<br />
ing, and in small portions. Each portion is added only after the<br />
evolution <strong>of</strong> nitrogen, due to the preceding portion, has ceased.<br />
When the reaction is complete the benzene formed is distilled<br />
through a downward condenser. The hydrocarbon passes over<br />
before much water distils and is collected in a test tube. After<br />
being dried with a little calcium chloride the benzene is distilled<br />
from a small distilling flask which has a condenser jacket slipped<br />
over the side tube and passes over almost completely at 81°. Yield<br />
Although practically important in other cases, the replacement <strong>of</strong><br />
an NH 2-group by hydrogen via the diazo-compound naturally has none<br />
in the example here given. Thus w-nitrotoluene (and from it m-<br />
toluidine) is obtained from y-toluidine by nitration <strong>of</strong> the acetylated base<br />
and replacement <strong>of</strong> the NH a-group (after elimination <strong>of</strong> the acetyl)<br />
by H, as shown above.<br />
g<br />
The course <strong>of</strong> the reaction is very remarkable. We must suppose<br />
that the diazotate is reduced to the unstable phenyldiimine which<br />
decomposes into benzene and nitrogen.<br />
C 6H 5.N=NONa 1 \ C 6H s.N=NH + N a 0 H >• C6H6 + N 2.<br />
Instead <strong>of</strong> by alkali stannite the diazo-group can be exchanged for<br />
hydrogen by prolonged boiling <strong>of</strong> the diazonium salt in alcohol, which is<br />
thereby oxidised to aldehyde.<br />
A secondary reaction yields at the same time phenol ether by the<br />
replacement <strong>of</strong> the diazonium group by alkoxyl. This is clearly<br />
analogous to the conversion <strong>of</strong> diazonium salts to phenols.<br />
+ HO.C 2H<br />
(e) Solid Phenyldiazonium Chloride.-—Aniline hydrochloride<br />
(3-5 g.) is dissolved in absolute alcohol (20 c.c.) and to the solution<br />
0-5 c.c. <strong>of</strong> alcoholic hydrogen chloride and, with ice cooling, 3 g. <strong>of</strong><br />
ethyl nitrite or 4 g. <strong>of</strong> isoamyl nitrite are successively added. After
SOLID PHENYLDIAZONIUM CHLOKIDE 287<br />
the mixture has stood for five to ten minutes the diazonium salt is<br />
completely precipitated by gradual addition <strong>of</strong> ether ; it is collected<br />
at the pump and washed, first with alcohol-ether (1:1) and then<br />
with ether alone. The salt is kept moist with ether and only a small<br />
sample is dried on filter paper. The dried material is caused to<br />
explode by a blow or in a flame. Even the material which is moist<br />
with ether must not be touched with a spatula or other hard object.<br />
The diazonium salt on the filter is dissolved in ice-water and is<br />
used for the preparation <strong>of</strong> phenyldiazonium perbromide and phenyl<br />
azide (see below).<br />
When nitrous gases (from arsenious oxide and nitric acid, d. 1-35)<br />
are passed into a well-cooled suspension <strong>of</strong> aniline nitrate in water,<br />
and alcohol and ether are then added gradually, crystalline phenyldiazonium<br />
nitrate is obtained. At most only 2 g. <strong>of</strong> aniline are used,<br />
and <strong>of</strong> the diazonium salt only as much as covers well the tip <strong>of</strong> a<br />
knife-blade is dried on porous plate, after collecting at the pump and<br />
washing with alcohol-ether (1 : 1).<br />
The nitrate detonates on heating on a spatula or on being struck<br />
with a hammer. The chloride is less liable to explode, but it too<br />
must not be preserved in the dry state. In general, work with dry<br />
diazonium salts must be carried out cautiously.<br />
On account <strong>of</strong> their great lability the diazonium salts <strong>of</strong> the simple<br />
primary amines cannot be isolated from aqueous solution. On the<br />
other hand, they crystallise from alcohol when ether is added. Since<br />
the metallic salts <strong>of</strong> nitrous acid are insoluble in alcohol, its esters are<br />
used instead for diazotisation in alcohol. These esters are hydrolysed<br />
by acid with extraordinary rapidity and therefore behave almost like<br />
salts (see p. 147).<br />
The diazonium salts are colourless. Their aqueous solutions react<br />
neutral. If the acid is removed from the salts by means <strong>of</strong> alkali, very<br />
unstable diazonium hydroxides result, which can only be demonstrated<br />
in the solution during quite a short time. These hydroxides change by<br />
addition <strong>of</strong> alkali and elimination <strong>of</strong> water into salts <strong>of</strong> acid diazohydroxides,<br />
the so-called diazotates.<br />
H<br />
CBHK.N=NONa<br />
"Cl<br />
im<br />
Diazonium salt Diazonium<br />
hydroxide<br />
'°, C6H5.N=NONa .<br />
Sodium phenyldiazotate
288 DIAZONIUM HYDKOXIDBS AND DIAZOTATBS<br />
If, now, the diazotate solution so obtained is re-acidified, the diazonium<br />
salt is re-formed :<br />
r H -i<br />
C6H5.N=NONa 2H( > C6HS.N=NOH +NaCl<br />
L Cl J<br />
-H,O C6HS.N=N<br />
-> Cl<br />
An important reversible relationship therefore exists between the<br />
diazonium and diazohydroxide types.<br />
The diazohydroxide, which is formed from the diazonium hydroxide<br />
by isomerisation, is said to be the pseudo-base <strong>of</strong> the latter (Hantzsch),<br />
because although it is itself not a base (but rather an acid) it nevertheless<br />
combines with acid to form the diazonium salt.<br />
Before the diazo-compounds are further treated from a preparative<br />
point <strong>of</strong> view another rearrangement which members <strong>of</strong> this interesting<br />
class undergo will be discussed. By energetic treatment with strong<br />
alkali, phenyldiazotate is converted into the salt <strong>of</strong> an isomeric acid ; the<br />
isodiazotate type (Schraube and Schmidt) is produced. For many years<br />
the constitution <strong>of</strong> the iso-diazotates was the subject <strong>of</strong> a historic controversy<br />
between Bamberger and Hantzsch. Most chemists now regard<br />
the question as decided in favour <strong>of</strong> the latter's view that the isomerism<br />
is spatial and depends on the different arrangement <strong>of</strong> the C6H5- and<br />
OH-groups with respect to the fixed plane <strong>of</strong> the doubly bound nitrogen.<br />
The same conception had already provided an explanation <strong>of</strong> the<br />
isomerism <strong>of</strong> asymmetrically substituted oximes (pp. 343, 344). It<br />
coincides, in principle, with the theory <strong>of</strong> the m-£raws-isomerism <strong>of</strong><br />
ethylene derivatives (fumaric and maleic acids).<br />
According to this theory the labile normal diazotates are regarded<br />
as the syn- ( = cis-) compounds, the stable iso-diazotates as the anti-<br />
(= trans-) compounds.<br />
C6H5 ONa C6H5<br />
N= N N=N<br />
ONa<br />
Normal diazotate /so-diazotate<br />
Whilst the conversion <strong>of</strong> the simple phenyl-syw-diazotate into its<br />
isomeride requires strong alkali, the syn-iovms <strong>of</strong> other diazotates are<br />
so labile that, almost instantaneously after formation from the diazonium<br />
salts, they change into the anti-form and hence can never be obtained in<br />
solution. An important example <strong>of</strong> this change is described under (/),<br />
namely, y-nitrophenyldiazotate, which, on coupling with jS-naphthol,<br />
yields the much-used dye " para-red ".
PHENYLDIAZONIUM PBKBKOMIDB 289<br />
Phenyldiazonium Perbromide .•—To a fresh ice-cold solution <strong>of</strong> one<br />
<strong>of</strong> the solid diazonium salts, prepared as described above, or to the<br />
diazo-solution from 2 g. <strong>of</strong> aniline, there is added the solution <strong>of</strong><br />
1-5 c.c. <strong>of</strong> bromine in 15 c.c. <strong>of</strong> potassium bromide solution (25 per<br />
cent), with ice cooling, until precipitation <strong>of</strong> dark-coloured oil ceases.<br />
The aqueous solution is then decanted ; when the residual perbromide<br />
is washed a few times with ice-water it crystallises.<br />
In order to convert it into phenyl azide (" diazobenzeneimide ")<br />
the perbromide is added in three or four portions to about 10 c.c. <strong>of</strong><br />
well-cooled concentrated ammonia solution. A vigorous reaction<br />
takes place, resulting in the formation <strong>of</strong> the pungent smelling<br />
phenyl azide, which is purified by steam distillation. It can also<br />
be distilled in a vacuum without decomposition. Since it explodes<br />
when rapidly heated it must be handled cautiously.<br />
The bromides <strong>of</strong> organic bases form with bromine insoluble perbromides,<br />
in the present case the addition compound C6H5.N=N .<br />
Br.Br2<br />
The mechanism <strong>of</strong> the reaction with ammonia is as follows. The<br />
perbromide bromine is converted into hypobromite and at the same<br />
time the diazonium salt undergoes rearrangement to syw-diazohydroxide,<br />
which immediately couples with NH3 to give phenyltriazene (" diazobenzeneamide<br />
"). The latter is then dehydrogenated by the hypobromite<br />
yielding phenyl azide (Dimroth) :<br />
C6H5.N==N 3NH3 C6H5.N=NOH + 2 NH4Br + NH40Br ,<br />
Br.Br2 2H,o<br />
C6HS.N:NOH + NH3 —>- C6H5.N:N.NH2 + H2O ,<br />
C6HB.N:N.NH2 + NH4OBr > C6H5.N< < | || + NH4<br />
By very careful hydrogenation (with stannous chloride in ethereal<br />
hydrogen chloride) phenyl azide has been converted into the exceedingly<br />
sensitive phenyltriazene (Dimroth), which, as has been shown, can<br />
be reconverted into the former by denydrogenation. As in the case<br />
<strong>of</strong> the aliphatic diazo-compounds, an open chain structural formula<br />
has lately also been assigned to hydrazoic acid and its esters, so that<br />
the changes just mentioned may be formulated as follows :<br />
+ 2H<br />
C6HB.N=N=N C6H5.N=N—NH2 .<br />
-2H<br />
Phenylazide is best prepared from phenylhydrazine (p. 299).
290 AKYL AZIDBS<br />
The aryl azides are very reactive compounds. By the action <strong>of</strong><br />
acids, for example, they lose the two terminal N-atoms as N2 ; the<br />
residual C6H5N C6H5.N=N—NH.CH3.<br />
Diethyl malonate reacts with azides to form triazolone derivatives,<br />
noteworthy because <strong>of</strong> their interesting tautomeric relationships<br />
(Dimroth).<br />
C6HS.N3 + CH2.(COOC2H5)2 —• C6H5-N<<br />
" 3—COOC,H5<br />
This condensation is completely analogous to that <strong>of</strong> ethyl diazoacetate,<br />
mentioned on p. 281, and, in general, azides and aliphatic<br />
diazo-compounds are strikingly similar in the manner in which they<br />
react with unsaturated substances like acetylenes, define derivatives,<br />
and hydrogen cyanide to yield heterocyclic compounds.<br />
(/) Sodium ^-Nitrophenyl-awfo'-Diazotate. 1 —0 N<br />
NONa<br />
^-Nitraniline (14 g.; 0-1 mole) is dissolved by heating in 60 c.c. <strong>of</strong><br />
hydrochloric acid (30 c.c. <strong>of</strong> concentrated acid and 30 c.c. <strong>of</strong> water)<br />
and the solution is poured into a small filter jar containing 80 g. <strong>of</strong><br />
ice. The solution is now diazotised at 5°-10° with the solution <strong>of</strong><br />
8 g. <strong>of</strong> sodium nitrite in 20 c.c. <strong>of</strong> water added in one lot with<br />
vigorous stirring. After it has been ascertained that the diazotisation<br />
is complete the solution is poured, with stirring, into 400 c.c. <strong>of</strong><br />
approximately 4iV^-sodium hydroxide solution which has been<br />
warmed to 40°-50°. As the mixture cools the awfo'-diazotate is<br />
deposited in the form <strong>of</strong> beautiful golden plates. After several hours<br />
1 Schraube and Schmidt, Ber., 1894, 27, 518.
^-TOLUNITKILE FKOM ^-TOLUIDINE 291<br />
the salt is collected at the pump and washed with saturated brine.<br />
When dried on porous plate the substance can be preserved for any<br />
desired time, and can be freed from adherent sodium chloride<br />
by dissolution in alcohol at 60°, nitration <strong>of</strong> the solution, and<br />
evaporation <strong>of</strong> the solvent. Yield upwards <strong>of</strong> 18 g.<br />
Verify that the aqueous solution <strong>of</strong> the diazo salt does not couple<br />
with the sodium salt <strong>of</strong> j8-naphthol nor with a solution <strong>of</strong> E-salt. 1<br />
But if the dilute solution is acidified with hydrochloric acid and<br />
filtered from undissolved flocculent material an azo-dye results on<br />
renewed coupling. The combination with the phenol <strong>of</strong> the syw-diazotate<br />
which is first formed proceeds more rapidly than its rearrangement to<br />
the anti-ioim.<br />
4. ;p-TOLUNITRILE FROM ^-TOLUIDINE (SANDMEYER'S<br />
REACTION 2 )<br />
A solution <strong>of</strong> 55 g. <strong>of</strong> potassium cyanide in 100 c.c. <strong>of</strong> water is<br />
added gradually with continued warming to copper sulphate solution,<br />
prepared by heating 50 g. <strong>of</strong> the salt with 200 c.c. <strong>of</strong> water in a<br />
two-litre flask on the water bath. (Evolution <strong>of</strong> cyanogen ! Fume<br />
chamber !)<br />
While the cuprous cyanide solution is warmed gently (to 60°-70°)<br />
on the water bath, a solution <strong>of</strong> j>-tolyldiazonium chloride is prepared<br />
as follows : Heat 20 g. <strong>of</strong> j>-toluidine with a mixture <strong>of</strong> 50 g. <strong>of</strong><br />
concentrated hydrochloric acid and 150 c.c. <strong>of</strong> water until dissolution<br />
is complete. Immerse the solution in ice-water and stir vigorously<br />
with a glass rod so that the toluidine hydrochloride separates as far<br />
as possible in a microcrystalline form. Then cool the mixture in ice<br />
and diazotise with a solution <strong>of</strong> 16 g. <strong>of</strong> sodium nitrite in 80 c.c. <strong>of</strong><br />
water, added until the nitrous acid test with potassium iodide-starch<br />
paper persists. The diazonium chloride solution so obtained is<br />
poured during the course <strong>of</strong> about ten minutes into the warm cuprous<br />
cyanide solution, which is meanwhile shaken frequently. After the<br />
diazo-solution has been added the reaction mixture is heated under<br />
an air condenser on the water bath for a further quarter <strong>of</strong> an hour,<br />
and then the toluic nitrile is separated by distillation with steam<br />
(fume chamber, HCN!). The nitrile (which passes over as a<br />
yellowish oil) is extracted from the distillate with ether, the j>-cresol<br />
produced as a by-product is removed by shaking the ethereal extract<br />
twice with 2 i^-sodium hydroxide solution, the ether is evaporated,<br />
1 On R-acid, see p. 302. 2 Ber., 1884, 17, 2650; 1885, 18, 1490; 1889, 22, 2178.
292 ^-TOLUIC AND TBKBPHTHALIC ACIDS<br />
and, by staking the warm residue with a solution <strong>of</strong> 4 g. <strong>of</strong> stannous<br />
chloride in 10 c.c. <strong>of</strong> concentrated hydrochloric acid, the azotoluene<br />
which gives the material its yellow colour is removed. 1 The liquid<br />
is diluted with water and the toluic nitrile which soon solidifies is<br />
collected at the pump and dried on porous plate. If the material<br />
remains partly oily it is dissolved in ether and shaken again with<br />
sodium hydroxide solution in order to remove stannous chloride.<br />
The ethereal solution is then dried and the nitrile is distilled. Boiling<br />
point 218°. Melting point 38°. Yield 12-14 g.<br />
Benzonitrile.—In the same apparatus benzonitrile can be prepared<br />
in a corresponding yield from the diazonium chloride solution<br />
obtained from 18-6 g. <strong>of</strong> aniline. Liquid boiling at 186°.<br />
^-Toluic Acid.—If the hydrolysis <strong>of</strong> a nitrile to an acid has not<br />
already been carried out (benzyl cyanide ->phenylacetic acid, p. 140)<br />
this process should be learned here.<br />
In a small round-bottomed flask mix 20 c.c. <strong>of</strong> concentrated<br />
sulphuric acid with 10 c.c. <strong>of</strong> water and add 5-5 g. <strong>of</strong> toluic nitrile<br />
gradually in small portions. Then heat the mixture to boiling under<br />
reflux condenser for about one hour on the sand bath or on wire<br />
gauze. After cooling, dilute with water, collect the crystalline acid<br />
at the pump, remove any amide which may be present by dissolving<br />
the crude material in dilute alkali solution and filtering, then<br />
precipitate the toluic acid from the filtrate with hydrochloric acid.<br />
A purer product is obtained by hydrolysis for five hours at 150° (in<br />
the oil bath). For purification dissolve the material (not previously<br />
dried) in the minimum quantity <strong>of</strong> boiling alcohol, add water to the<br />
boiling solution until turbidity just fails to persist, and continue the<br />
boiling for a few minutes longer with a little animal charcoal, but do<br />
not add the latter while the solution is boiling. Filter and allow the<br />
filtrate to cool. The acid which crystallises melts at 177°. Yield4 g.<br />
The best preparative method <strong>of</strong> obtaining terephthalic acid is to<br />
oxidise the sodium salt <strong>of</strong> y-toluic acid with permanganate at the temperature<br />
<strong>of</strong> the water bath. In the same way toluene can be converted<br />
into benzoic acid, and an important technical example <strong>of</strong> this reaction<br />
is the oxidation, <strong>of</strong> o-tolylsulphonamide to saccharin.<br />
Henle, <strong>Org</strong>an, chem. Praktikum, 3rd Ed., p. 149.
THE SANDMBYEK KBACTION 293<br />
By permanganate oxidation long side chains are broken down to<br />
carboxyl groups attached to the ring. The biological degradation <strong>of</strong><br />
aj-aryl-fatty acids proceeds in accordance with the j8-oxidation rule<br />
(F. Knoop).<br />
Sandmeyer's Reaction.—The ready formation <strong>of</strong> iodobenzene in the<br />
above method is due to the spontaneous decomposition <strong>of</strong> the diazonium<br />
iodide into iodobenzene and nitrogen<br />
> C6HS<br />
In the bromide and chloride, however, after the nitrogen has been<br />
eliminated, the halogen wanders only to a slight extent to the " gap "<br />
so left, and the formation <strong>of</strong> phenol predominates.<br />
In 1884, Sandmeyer, however, made the important discovery that in<br />
the presence <strong>of</strong> the corresponding cuprous salt chlorine and bromine are<br />
also directed to the nucleus. This catalytic action has not yet been<br />
explained. Perhaps a double salt is formed, or else a complex salt in<br />
which the halogen is more firmly bound than in the simple halide.<br />
According to Gattermann, the cuprous salt may be replaced by copper<br />
powder. In general, the decomposition <strong>of</strong> labile diazo-compounds, by<br />
elimination <strong>of</strong> elementary nitrogen, is accelerated by copper.<br />
The replacement <strong>of</strong> the amino-group by halogen is a process <strong>of</strong> great<br />
importance. There is no other preparative method <strong>of</strong> obtaining the<br />
aromatic iodo-compounds. The introduction <strong>of</strong> chlorine and bromine<br />
in this way is important because single homogeneous halogen derivatives<br />
can be obtained from the amine, whereas we know that such is not<br />
always the case when the parent substance is directly chlorinated or<br />
brominated. Thus when toluene is brominated (in the ring) both<br />
o- and y-bromotoluene are formed, and can be separated only with difficulty.<br />
But by means <strong>of</strong> Sandmeyer's reaction, however, the two<br />
toluidines yield exclusively o- or y-bromotoluene ; m-bromotoluene,<br />
moreover, can only be obtained from m-toluidine.<br />
Sandmeyer's synthesis <strong>of</strong> aromatic nitriles is far more elegant than<br />
the removal <strong>of</strong> water from the ammonium salts <strong>of</strong> carboxylic acids,<br />
which latter reaction is also applicable to benzene derivatives. In particular,<br />
the former synthesis permits <strong>of</strong> the preparation <strong>of</strong> carboxylic<br />
acids via the nitriles, and so provides a complete substitute for Kolbe's<br />
synthesis (alkyl halide and potassium cyanide), which is inapplicable to<br />
aromatic compounds. The simplest example is the conversion <strong>of</strong> aniline<br />
into benzoic acid. The converse transformation is H<strong>of</strong>mann's degradation<br />
(benzamide ->aniline, see p. 152).<br />
5. ARSANILIC ACID FROM p-NITRANILINE 1<br />
p-Nitrophenylarsinic Acid.-—Diazotise 13-8 g. <strong>of</strong> p-nitraniline in<br />
the manner described for the preparation <strong>of</strong> the awfo'-diazotate<br />
1 H. Bart, Annalen, 1922, 429, 95.
294 AKSANILIC ACID<br />
(p. 290). Dilute to one litre with water and ice, add 4iV-sodium<br />
hydroxide solution, with stirring, until the free acid is so far neutralised<br />
that Congo paper just fails to turn blue, and then pour the<br />
diazonium salt solution in a thin stream into a large filter jar containing<br />
800 c.c. <strong>of</strong> 5 per cent solution <strong>of</strong> hydrogen disodium arsenite. 1<br />
Stir the mixture with a glass rod. A vigorous evolution <strong>of</strong> nitrogen<br />
takes place and the reaction is complete almost instantaneously.<br />
Now concentrate the liquid to about 400 c.c. in a porcelain basin, and<br />
precipitate resinous by-products from the dark-coloured solution by<br />
making feebly acid with hydrochloric acid. When the precipitation<br />
is finished filter the liquid (now lighter in colour) through a folded<br />
filter and concentrate the filtrate, which is now acid to Congo paper,<br />
until crystallisation begins. On cooling 8-10 g. <strong>of</strong> faintly yellow<br />
needles <strong>of</strong> p-nitrophenylarsinic acid separate. If the solution is<br />
still too strongly coloured after filtration, boil with animal charcoal<br />
before concentrating.<br />
The product should be readily soluble in cold sodium carbonate<br />
solution. Otherwise arsenic trioxide, which can thus be removed, is<br />
present.<br />
Reduction.'—Place 10 g. <strong>of</strong> iron powder (ferrum reductum), 100 c.c.<br />
<strong>of</strong> water, and 2 c.c. <strong>of</strong> concentrated hydrochloric acid in a 250 c.c.<br />
flask and attach to it the extraction apparatus shown in Fig. 27<br />
(p. 35). Into the thimble put 6-5 g. <strong>of</strong> nitrophenylarsinic acid.<br />
Heat the contents <strong>of</strong> the flask to boiling so that about every two<br />
seconds a (yellow) drop <strong>of</strong> solution falls back into the flask. The<br />
extraction should be complete in about half an hour. Continue the<br />
boiling for a quarter <strong>of</strong> an hour longer, add 25 c.c. <strong>of</strong> 5iV-sodium<br />
hydroxide solution, boil for five mmutes more, and pour <strong>of</strong>f from the<br />
bulk <strong>of</strong> the iron sludge into a Buchner funnel. Then boil out the<br />
sludge twice with 100 c.c. portions <strong>of</strong> hot dilute sodium hydroxide<br />
solution (about 0-2 N). Now concentrate the combined filtrates to<br />
75 c.c, add concentrated hydrochloric acid until the liquid is just<br />
acid to Congo paper, and neutralise the excess <strong>of</strong> mineral acid with<br />
sodium acetate solution. The arsanilic acid separates on prolonged<br />
keeping. Kecrystallise it from 40-50 c.c. <strong>of</strong> hot water, adding a little<br />
animal charcoal if necessary. Yield 3-4 g.<br />
Experiments—Demonstrate the presence <strong>of</strong> the primary NH2group<br />
by dissolving a small amount <strong>of</strong> the acid in a little sodium<br />
1 Prepared by dissolving 23'5 g. <strong>of</strong> powdered arsenious oxide in 240 c.c. <strong>of</strong><br />
previously titrated 2 i^-sodium hydroxide solution and diluting to 800 c.c.
SALVAKSAN 295<br />
hydroxide solution, adding approximately one equivalent <strong>of</strong> sodium<br />
nitrite, cooling the solution by addition <strong>of</strong> ice and acidifying with<br />
hydrochloric acid. The diazonium solution when mixed with an<br />
alkaline solution <strong>of</strong> j8-naphthol produces the corresponding red<br />
azo-dye. (Formulate!)<br />
The introduction <strong>of</strong> the arsinic acid group into the aromatic nucleus<br />
is <strong>of</strong> great interest in connexion with the therapeutic application <strong>of</strong><br />
arsenic compounds in combating certain infectious diseases (atoxyl =<br />
sodium arsanilate ; salvarsan).<br />
Arsanilic acid was first synthesised, in very poor yield, by melting<br />
arsenic acid with aniline :<br />
Compare this process with sulphonation and nitration, and note<br />
especially the difference between nitrogen and arsenic, which are introduced<br />
respectively as the neutral nitro-group and the corresponding<br />
hydrate, viz. the dibasic arsinic acid group.<br />
The reduction <strong>of</strong> the arsinic acids to arsenobenzenes corresponds to<br />
that <strong>of</strong> the nitro-compounds to azo-compounds :<br />
^ < f + 6 H2O .<br />
OH \ / \ /<br />
If the y-hydroxy-compound, obtained by boiling diazotised arsanilic<br />
acid with water, is nitrated, and the nitro-group so introduced is reduced<br />
to the amino-group, further reduction yields the corresponding arsenocompound,<br />
salvarsan. (Formulate these reactions !)<br />
The introduction <strong>of</strong> the arsinic acid group into the benzene ring,<br />
which generally takes place in Bart's reaction as above described,<br />
probably involves the formation <strong>of</strong> an intermediate product having a<br />
structure analogous to that <strong>of</strong> diazosulphonate (p. 297, footnote). This<br />
intermediate product does not undergo rearrangement to the stable<br />
anti-ioma. so rapidly as does the diazosulphonate, but decomposes with<br />
evolution <strong>of</strong> nitrogen.<br />
C6Hs.N=N + NaAs^-ONa —> C6H5.N=N.As^-ONa + NaCl<br />
Cl M)H \<br />
>- C6Hs.As^-ONa + N2 .<br />
M)H
296 PHBNYLHYDKAZINB<br />
6. PHENYLHYDRAZINE 1<br />
Dissolve 47 g. (0-5 mole) <strong>of</strong> aniline in a mixture <strong>of</strong> concentrated<br />
hydrochloric acid and water (100 c.c. <strong>of</strong> each) and diazotise the wellcooled<br />
solution, in the manner repeatedly described, with a solution<br />
<strong>of</strong> 38 g. <strong>of</strong> sodium nitrite in 100 c.c. <strong>of</strong> water. Before diazotising<br />
the aniline, prepare as concentrated a solution as possible in water<br />
<strong>of</strong> 158 g. (1-25 mole) <strong>of</strong> neutral anhydrous sodium sulphite or <strong>of</strong><br />
315 g. <strong>of</strong> the hydrated (7 H20) salt. The sulphite content <strong>of</strong> this<br />
solution is equivalent to the amount <strong>of</strong> hydrochloric acid taken, and<br />
represents a 25 per cent excess in respect <strong>of</strong> the aniline.<br />
The cheapest way <strong>of</strong> preparing the sulphite solution is to neutralise<br />
commercial bisulphite solution, the content <strong>of</strong> which must have been<br />
determined by titration, with the necessary amount <strong>of</strong> sodium<br />
hydroxide solution. Of good 40 per cent bisulphite solution 325 g.<br />
are required, and are neutralised with 110 g. <strong>of</strong> 50 per cent sodium<br />
hydroxide solution. The success <strong>of</strong> the experiment depends on the<br />
correct preparation <strong>of</strong> the sulphite solution. Pour the freshly<br />
prepared diazonium chloride solution rapidly into the cold sulphite<br />
solution contained in a round-bottomed flask (capacity 2 1.). A<br />
sample <strong>of</strong> the orange-red solution formed should not become turbid<br />
when boiled in a test tube. If, nevertheless, turbidity does develop,<br />
add more sulphite. Now add gradually 100 c.c. <strong>of</strong> concentrated<br />
hydrochloric acid in small portions with shaking. The colour <strong>of</strong> the<br />
solution is thus changed to yellow. Now heat on the water bath,<br />
add a few cubic centimetres <strong>of</strong> glacial acetic acid, and make the<br />
solution lighter in colour by dropping in a little zinc dust. Filter<br />
while hot, add without delay 300 c.c. <strong>of</strong> concentrated hydrochloric<br />
acid to the filtrate, and allow it to cool slowly.<br />
Filter the crystals <strong>of</strong> phenylhydrazine hydrochloride at the pump,<br />
press the salt as dry as possible on the funnel, wash with hydrochloric<br />
acid (1: 3), and then decompose in a separating funnel containing<br />
150 c.c. <strong>of</strong> 4 i^-sodium hydroxide solution and ether. Extract<br />
twice with ether, dry the ethereal solution <strong>of</strong> the base with anhydrous<br />
potassium carbonate, and finally distil the phenylhydrazine in vacuo,<br />
using an Anschiitz-Thiele adapter (Fig. 17, p. 22). Boiling point<br />
120 o /12 mm. Yield about 30 g.<br />
After being cooled for some time in water the preparation should<br />
solidify completely and it should dissolve in dilute acetic acid with-<br />
1 E. Fischer, Annalen, 1877, 190, 78.
PHBNYLHYDKAZINB 297<br />
out turbidity. Melting point 23°. Distillation under atmospheric<br />
pressure is always accompanied by decomposition (N2, NH3,<br />
NH2.C6H5, and C6H6) and does not yield pure phenylhydrazine.<br />
The method <strong>of</strong> V. Meyer, reduction <strong>of</strong> the diazonium chlorides<br />
to arylhydrazines with strongly acid stannous chloride solution, is<br />
less elegant. The difference in the actions <strong>of</strong> stannous salt in acid<br />
and in alkaline solution should be noted.<br />
Emil Fischer's classical method here described proceeds via the<br />
phenyl awta'-diazosulphonate 1 which had already been prepared by<br />
Strecker and R6merx and frequently separates in beautiful orangeyellow<br />
crystals at the beginning <strong>of</strong> the reaction.<br />
6 5<br />
C6HS.N<br />
Cl + Na2SO3 >• || +NaCl.<br />
N.SO3Na<br />
The sulphurous acid liberated in the second phase <strong>of</strong> the process by<br />
the addition <strong>of</strong> hydrochloric acid hydrogenates the azo-double bond,<br />
probably via an addition product A, <strong>of</strong> which one SO3H-group is easily<br />
removed by hydrolysis with the formation <strong>of</strong> the sodium salt <strong>of</strong> phenylhydrazine<br />
sulphonic acid.<br />
A C6H5.N—NHSOgNa H '°> CH5.NH—NH.SOsNa<br />
A 8O3H + H2SO4.<br />
The hydrogen evolved by the zinc dust serves to complete the hydrogenation.<br />
Finally, the more firmly bound sulphonic group is also<br />
removed, as sulphuric acid, by the hqt concentrated hydrochloric acid.<br />
Phenylhydrazine is prepared on a large scale by this method. The<br />
base is an indispensable reagent for characterising aldehydes and ketones<br />
(phenylhydrazones) and for many syntheses, particularly for the technical<br />
production <strong>of</strong> antipyrine and pyramidone. Study the course <strong>of</strong><br />
these syntheses. The salts <strong>of</strong> phenylhydrazine contain only one molecule<br />
<strong>of</strong> acid.<br />
Experiments—Add three drops <strong>of</strong> glacial acetic acid to a mixture<br />
<strong>of</strong> five drops <strong>of</strong> phenylhydrazine and 5 c.c. <strong>of</strong> water. Then add two<br />
drops <strong>of</strong> benzaldehyde (on a glass rod) and shake. At first a milMness<br />
appears, but very soon a flocculent precipitate <strong>of</strong> benzylidene-<br />
1 The diazonium sulphite CeH5.N = N which is doubtless formed first, under-<br />
SO3Na<br />
goes spontaneous rearrangement to the diazotate-form ; the same holds for the<br />
arsenites (p. 295) and cyanides.<br />
CeH5.N = N -> CeH5.N=N.CN.<br />
CN
298 OSAZONBS<br />
phenylhydrazone is formed. In this way very small quantities <strong>of</strong><br />
benzaldehyde may be detected.<br />
In sugar chemistry phenylhydrazine has become <strong>of</strong> outstanding importance<br />
for the separation, characterisation, and transformation <strong>of</strong> the<br />
various kinds <strong>of</strong> sugars. The fundamental results <strong>of</strong> this domain could<br />
hardly have been obtained without this reagent. When one molecule<br />
<strong>of</strong> a sugar reacts with one molecule <strong>of</strong> phenylhydrazine a normal hydrazone<br />
is formed, e.g.<br />
CH2.OH.(CH.OH)4.CHO + C6H5.NH.NH2<br />
Dextrose = CH2.OH.(CH.OH)4.CH:N.NH.C6H5 + H2O .<br />
If, however, an excess <strong>of</strong> phenylhydrazine is used, the base has an<br />
oxidising eflect on the sugar, i.e. it removes hydrogen so that, for example,<br />
the CH.OH-group adjacent to the aldehyde group in the above<br />
example is dehydrogenated to a ketonic group which again reacts with<br />
the hydrazine. The substances formed, the osazones, have already been<br />
mentioned on p. 224. In the above case we obtain :<br />
CH2.OH.(CH.OH)3.C—CH=N.NH.C6H5<br />
II<br />
N—NH.C6H5<br />
Like all hydrazones, osazones lose phenylhydrazine when heated<br />
with hydrochloric acid. Naturally, it is not the sugar originally taken<br />
which is thus recovered, but an oxidation product, a so-called osone.<br />
In the example chosen the osone is:<br />
CH2.OH.(CH.OH)3.CO.CHO.<br />
When this is reduced it is not the ketonic group which is aflected<br />
(which would regenerate the original sugar), but rather the aldehyde<br />
group, and the compound<br />
CH2.OH.(CH.OH)3.CO.CH2.OH<br />
is obtained.<br />
An aldose has been converted into a ketose, d-glucose into d-fructose.<br />
Experiment.-—Heat a solution <strong>of</strong> 2 g. <strong>of</strong> phenylhydrazine in<br />
dilute acetic acid (1-5 c.c. <strong>of</strong> acid, 15 c.c. <strong>of</strong> water) with 1 g. <strong>of</strong><br />
rf-glucose dissolved in 5 c.c. <strong>of</strong> water on the water bath at 80°. After<br />
about twenty minutes the osazone begins to separate in fine small<br />
yellow needles. After the lapse <strong>of</strong> an hour collect the crystals at the<br />
pump, wash with water, and dry in the air. Melting point 205°.<br />
Phenylhydrazine can donate hydrogen, but, in certain circumstances,<br />
can also accept it; it can, therefore, both reduce and oxidise. In the<br />
former case benzene and nitrogen are formed by way <strong>of</strong> the already
SYNTHESIS OF INDOLES 299<br />
mentioned phenyldiimine (action <strong>of</strong> copper sulphate, ferric chloride,<br />
Fehling's solution, ammoniacal silver nitrate solution) ; in acid solution<br />
diazonium salts can be re-formed by careful oxidation.<br />
Experiment. Benzene from Phenylhydrazine.—Allow 5 g. <strong>of</strong><br />
phenylhydrazine, dissolved in a mixture <strong>of</strong> 5 c.c. <strong>of</strong> glacial acetic<br />
acid and 10 c.c. <strong>of</strong> water, to run slowly into an ordinary distilling<br />
flask in which a solution <strong>of</strong> 25 g. <strong>of</strong> copper sulphate in 75 c.c. <strong>of</strong><br />
water is heated to the boiling point. A downward condenser is<br />
attached to the flask. A vigorous evolution <strong>of</strong> nitrogen takes place<br />
and the benzene at once begins to distil with the steam. Collect and<br />
purify (as described on p. 286). Yield 2-3 g.<br />
Like hydrazobenzene, phenylhydrazine decomposes when overheated<br />
; one molecule hydrogenates a second.<br />
As in the case <strong>of</strong> hydrazobenzene, the decomposition is catalytically<br />
accelerated by finely divided platinum.<br />
Test the behaviour <strong>of</strong> phenylhydrazine towards Fehling's solution<br />
and towards ammoniacal silver solution.<br />
If sodium nitrite solution is run drop by drop into an aqueous<br />
solution <strong>of</strong> a phenylhydrazine salt the yellow, poisonous a-nitrosophenylhydrazine<br />
is formed ; it can be converted, with elimination <strong>of</strong> water,<br />
into fhenyl azide.<br />
C6H5.N.NH. C6H5.N—N<br />
I -+ V -<br />
NO N<br />
For details about the azides see p. 290.<br />
Experiment. E. Fischer's Indole Synthesis.-—Mix 2 g. <strong>of</strong> phenylhydrazine<br />
with 2 c.c. <strong>of</strong> acetone in a test tube. Water is eliminated<br />
and a turbidity appears. Suspend the tube in the boiling water bath<br />
for forty-five minutes, then add 6 g. <strong>of</strong> dry zinc chloride and heat the<br />
mixture for a few minutes with stirring in an oil bath at 180°. Now<br />
wash the dark-coloured melt into a small round-bottomed flask with<br />
four volumes <strong>of</strong> dilute hydrochloric acid and separate the resultant<br />
a-methylindole by distillation with steam. The substance collects as<br />
an oil which soon solidifies. After drying crystallise it from a little<br />
petrol ether. Melting point 59°.<br />
Pine-Wood Reaction.—Dip a small piece <strong>of</strong> pine-wood in concentrated<br />
hydrochloric acid and then hold it in the vapour from boiling
300 METHYL OKANGE<br />
water containing a little methylindole. An intense red colour is<br />
produced.<br />
The mechanism <strong>of</strong> this elegant, surprising, and widely applicable<br />
synthesis <strong>of</strong> indole derivatives was only explained recently (E. Robinson).<br />
It must be assumed that the keto-phenylhydrazones, in tautomeric<br />
hydrazo-form, undergo a species <strong>of</strong> benzidine rearrangement which, like<br />
the latter, can <strong>of</strong>ten occur even in dilute acid solution, e.g. with the<br />
phenylhydrazone <strong>of</strong> pyruvic acid.<br />
The last-formulated hypothetical diamine is transformed into an<br />
indole derivative by loss <strong>of</strong> ammonia, after the fashion <strong>of</strong> well-known<br />
analogues (1 : 4-diaminobutane to pyrrolidine).<br />
7. PREPARATION OF AZO-DYES<br />
(a) Helianthine.—Dissolve 20 g. <strong>of</strong> sulphanilic acid in 50 c.c. <strong>of</strong><br />
2 i^-sodium hydroxide solution and add a solution <strong>of</strong> 8 g. <strong>of</strong> sodium<br />
nitrite in 100 c.c. <strong>of</strong> water. Cool in ice and pour into 50 c.c. <strong>of</strong><br />
2iV-hydrochloric acid. Next mix the solution <strong>of</strong> sodium diazobenzenesulphonate,<br />
so produced, with a previously prepared solution<br />
<strong>of</strong> 12 g. <strong>of</strong> dimethylaniline in 100 c.c. <strong>of</strong> iV-hydrochloric acid,<br />
and make the mixture distinctly alkaline with sodium hydroxide.<br />
Very soon the sodium salt <strong>of</strong> the dye separates in beautiful orangebrown<br />
crystalline leaflets. Leave for several hours, then filter as<br />
dry as possible at the pump and, if desired, recrystallise the product,<br />
which is already fairly pure, from a little water. The yield is nearly<br />
quantitative.<br />
Alternatively, dissolve 12 g. <strong>of</strong> dimethylaniline in a suspension <strong>of</strong><br />
20 g. <strong>of</strong> sulphanilic acid in 100 c.c. <strong>of</strong> water, cool in ice, and add the<br />
nitrite solution slowly. The sodium salt <strong>of</strong> the dye then separates<br />
directly.<br />
As a variation diazotised anthranilic acid may be converted into<br />
" methyl red " by coupling with dimethylaniline.<br />
The azo-dye obtained is the indicator methyl orange which is much<br />
used in alkalimetry. The yellow dilute solution <strong>of</strong> helianthine is turned<br />
red by acids.
ANALYSIS OF AZO-DYBS 301<br />
The coupling proceeds according to the equation :<br />
NaO.s/ \—N=N0H<br />
HO,S< V-N=N<br />
The yellow sodium salt is derived from this " azo- " form, whilst a<br />
red quinonoid salt is formed by the action <strong>of</strong> acids.<br />
HO3S< V N N > N <<br />
Probably the free acid, which is also red, has the constitution <strong>of</strong> an<br />
intramolecular quinonoid salt.<br />
HN- —N<br />
I PIT<br />
I / b±1 3<br />
O2S 0 N<<br />
\CH3<br />
In view <strong>of</strong> the exceptional technical importance <strong>of</strong> the innumerable<br />
azo-dyes which are produced in this way, a general method, in use for<br />
their analysis, deserves mention. All azo-dyes are split on reduction<br />
by stannous chloride or also by sodium hydrosulphite ; four hydrogen<br />
atoms are taken up and two molecules <strong>of</strong> primary amine are formed<br />
(in the case <strong>of</strong> polyazo-dyes correspondingly more). In contrast to the<br />
simple azo-dyes amino- and hydroxy-hydrazo-compounds are so unstable<br />
towards reducing agents that they are immediately decomposed<br />
at the hydrazine linkage. As a glance at the formula shows, helianthine,<br />
when reduced in this manner, yields sulphanilic acid and<br />
y-dimethylphenylenediamine. It is evident, then, that the nitrogen<br />
introduced by diazotisation ultimately appears in the " azo-component"<br />
(here dimethylaniline) as an additional NH2-group, whilst the diazotised<br />
amine (the sulphanilic acid) is recovered in its original form.<br />
Experiment.-—Dissolve 3 g. <strong>of</strong> helianthine in the minimum amount<br />
<strong>of</strong> hot water and add hot stannous chloride solution (8 g. in 20 c.c. <strong>of</strong><br />
concentrated hydrochloric acid) until decolorisation takes place. On<br />
cooling and rubbing with a glass rod sulphanilic acid crystallises.<br />
After some time collect it at the pump. Add excess <strong>of</strong> concentrated<br />
alkali hydroxide solution to the nitrate and extract it with ether.
302 CONGO BED<br />
Dry the ethereal solution with a small piece <strong>of</strong> potassium hydroxide<br />
and evaporate the ether, when the diamine formed algng with the<br />
sulphanilic acid remains ; it can be recognised by the colour reaction<br />
described on p. 319 (Wurster's red). It becomes crystalline on<br />
cooling. Its acetyl derivative, which is obtained by warming the<br />
crude base on the water bath for a short time with 0-5 c.c. <strong>of</strong> acetic<br />
anhydride (in a test tube,) is also suitable for characterising the<br />
diamine. The solution is diluted with water and, since the acetyl<br />
compound in virtue <strong>of</strong> the —N
COUPLING OF ANILINE 303<br />
Congo red is a stronger acid than methyl orange ; the change <strong>of</strong><br />
colour requires a higher hydrogen ion concentration. Congo paper<br />
therefore serves to distinguish between organic acids and mineral acids.<br />
Congo red is the prototype <strong>of</strong> the " substantive " cotton dyes <strong>of</strong><br />
the benzidine group. The tinctorially valuable property <strong>of</strong> dyeing<br />
cotton directly (i.e. without a mordant) is doubtless to be attributed<br />
to the intimate adsorption <strong>of</strong> the colloidal particles <strong>of</strong> the dye on the<br />
fibre.<br />
(c) /3-Naphthol Orange.—Pour a mixture <strong>of</strong> 10 g. <strong>of</strong> sulphanilic<br />
acid with nitrite (4 g.), prepared as described under (a), with ice<br />
cooling and stirring, into 50 c.c. <strong>of</strong> 4 iV-hydrochloric acid. Mix the<br />
sludge <strong>of</strong> 2>-diazobenzenesulphonic acid rather quickly, with stirring,<br />
with an alkaline solution <strong>of</strong>/3-naphthol (8 g. in 100 c.c. <strong>of</strong> 2iV-sodium<br />
hydroxide solution) at room temperature. After a short time<br />
crystallisation <strong>of</strong> the sodium salt <strong>of</strong> the dye sets in (orange-yellow<br />
platelets). Complete the process by addition <strong>of</strong> saturated brine.<br />
Collect the product at the pump and wash with cold water. Yield<br />
15-16 g.<br />
THE COUPLING OF ANILINE<br />
As we have already seen in the case <strong>of</strong> aniline, primary aromatic<br />
amines do not couple normally; a triazene derivative, diazoaminobenzene,<br />
is produced by linkage through the NH2-group just as in the<br />
case <strong>of</strong> aliphatic amines, e.g. dimethylamine :<br />
C6H5.N:NOH + NH2.C6H5[HN.(CH3)2] ^C6HS.N:N.NH.C6H5[.N.(CH3)2].<br />
Compounds <strong>of</strong> this type are soon reconverted by acids into diazonium-<br />
and amine-salt. In the case <strong>of</strong> the diaryltriazenes this reconversion<br />
is already caused by a quite feebly acid reaction, e.g. that <strong>of</strong><br />
aniline salts in the presence <strong>of</strong> excess <strong>of</strong> base ; but under these conditions<br />
the diazonium salt can combine with the amine present in excess to<br />
form an azo-dye (Rosenhauer). The equation<br />
therefore gives information about the result only, but not about the<br />
mechanism <strong>of</strong> the reaction.<br />
Diazoaminobenzene and ^-Aminoazobenzene.—Diazotise 9-3 g.<br />
<strong>of</strong> aniline to the extent <strong>of</strong> one half under the usual conditions with<br />
half the amount <strong>of</strong> nitrite (3-8 g.) and add to the solution, with<br />
stirring, a solution <strong>of</strong> 25 g. <strong>of</strong> sodium acetate in 100 c.c. <strong>of</strong> water.
304 THBOKY OF DYEING<br />
After the liquid has become clear, filter at the pump, wash the<br />
yellowish-brown precipitate with water, and dry thoroughly, first<br />
on porous plate and then in a vacuum. Then recrystallise from<br />
petrol ether (boiling point .50°-60°) decolorising with a little animal<br />
charcoal. Melting point 98°. Heat a sample with dilute hydrochloric<br />
acid in a test tube.<br />
Further, add 1 g. <strong>of</strong> dry finely powdered aniline hydrochloride to<br />
5 g. <strong>of</strong> aniline and heat the mixture in a test tube on the water bath<br />
at 30°, with 2 g. <strong>of</strong> dry diazoaminobenzene. Continue heating the<br />
frequently stirred mixture for half an hour. Then raise the temperature<br />
to 45° and heat again for half an hour. When now a<br />
sample no longer evolves nitrogen on heating with hydrochloric<br />
acid, dissolve the aniline by adding 24 c.c. <strong>of</strong> 10 per cent hydrochloric<br />
acid (6 c.c. <strong>of</strong> concentrated acid and 18 c.c. <strong>of</strong> water). Eecrystallise<br />
the aminoazobenzene hydrochloride, which remains undissolved, from<br />
100 parts <strong>of</strong> hot water to which a little hydrochloric acid has been<br />
added. In order to obtain the orange-yellow base decompose the<br />
salt with sodium carbonate.<br />
On the Theory <strong>of</strong> Dyes.—In carbon compounds absorption in the<br />
visible part <strong>of</strong> the spectrum, i.e. subjective colour, is conditioned by<br />
the presence <strong>of</strong> a so-called chromophoric group in the molecule. The<br />
nitroso-group is strongly chromophoric, the nitro-group much less so,<br />
whilst the azo-group is quite considerably chromophoric, but only in<br />
aromatic systems. Azomethane is colourless.<br />
The intensely red azobenzene, however, is no more a dye than is<br />
nitrosobenzene. In order to make it into a dye, another group is<br />
necessary which, in virtue <strong>of</strong> its chemical nature, confers affinity<br />
towards the fibre and at the same time deepens the colour. The most<br />
important <strong>of</strong> these groups, which are called auxochromes, are OH and<br />
NH2. We have encountered their auxochromic influence in the simple<br />
cases <strong>of</strong> o-nitrophenol and the nitranilines.<br />
Wool and silk are protein-like substances and hence are amphoteric.<br />
Accordingly, they can combine with acids as well as with bases. For<br />
this reason wool and silk can be dyed directly by dyes in virtue <strong>of</strong> their<br />
auxochromic groups.<br />
It is otherwise with cotton, which is almost chemically pure cellulose,<br />
and hence is chemically indifferent in a tinctorial sense. Here combination<br />
with the dye results from the use <strong>of</strong> mordants which are adsorbed<br />
colloidally on the fibre before dyeing. The mordant can then enter<br />
into chemical union with the dye as a complex compound. For an<br />
important group <strong>of</strong> acid dyes (p. 335) the mordants are chiefly metallic<br />
hydroxides, namely, those <strong>of</strong> chromium, aluminium, iron, antimony,<br />
tin, etc., whilst for basic dyes tannin is the usual mordant.
COUPLING KBACTION OF DIAZO-COMPOUNDS 305<br />
In all cases, however, besides the chemical combination, the physical<br />
action due to surface adsorption plays a decisive part.<br />
It is this action alone which enables a relatively small number <strong>of</strong><br />
dyes, the so-called substantive cotton dyes, to be absorbed directly by<br />
the unmordanted vegetable fibre. The most important <strong>of</strong> these dyes<br />
are the bis-azo dyes, such as Congo-red and related compounds, which<br />
are derived from doubly diazotised benzidine. In aqueous solution<br />
they are present as sols and are coUoidally adsorbed by the fibres as<br />
irreversible gels.<br />
ON THE COUPLING KEACTION OF THE DIAZO-COMPOUNDS<br />
In its simplest form this reaction, by means <strong>of</strong> which the extremely<br />
numerous technical azo-dyes are manufactured, consists in condensation<br />
<strong>of</strong> aromatic diazo-compounds with phenols or aromatic amines to<br />
form azo-compounds. From the labile diazo-system the very stable<br />
azo-complex is produced. The azo-dyes, therefore, are, without exception,<br />
derivatives <strong>of</strong> azobenzene or else <strong>of</strong> azonaphthalene, etc.<br />
It is a rule that combination with phenols takes place only in alkaline<br />
or neutral solution, whereas the aromatic amines couple in feebly acid<br />
solution (usually acetic acid).<br />
The simplest azo-dye—devoid <strong>of</strong> technical importance, however—<br />
is formed from phenyl diazotate and phenol; the diazo-group takes up<br />
the y-position—in the case <strong>of</strong> j8-naphthol the adjacent a- or o-position.<br />
y-Hydroxyazobenzene<br />
The coupling <strong>of</strong> aniline was already encountered above in connection<br />
with the testing <strong>of</strong> the diazonium solution for free amine ; after the<br />
addition <strong>of</strong> sodium acetate the presence <strong>of</strong> the latter was revealed by<br />
the appearance <strong>of</strong> the insoluble diazoaminobenzene.<br />
It cannot be decided with certainty whether in this case the diazonium<br />
salt itself couples or whether, more probably, we must assume<br />
a partial hydrolysis to diazohydroxide and acid in the feebly acid solution.<br />
Our deductions will be based on the second explanation.<br />
As follows from the preparation <strong>of</strong> helianthine, dimethylaniline<br />
condenses in exactly the same way as phenol: 'p-dimethylaminoazobenzene<br />
is formed.<br />
The azo-dyes derived from phenols are called acid dyes, those<br />
derived from amines basic dyes. But since, in industry, the starting<br />
materials, not only diazo-components (diazotised amines), but also azocomponents<br />
(coupled phenols or amines), are nearly always sulphonic<br />
acids, this distinction is pointless. The vast majority <strong>of</strong> the azo-dyes<br />
x
306 MECHANISM OF THE COUPLING<br />
actually belong to the class <strong>of</strong> acid dyes. The object <strong>of</strong> the sulphonic<br />
group is to make the dye soluble in the dye bath.<br />
The most important technical azo-dyes are derived from naphthalene,<br />
and indeed there is hardly any branch <strong>of</strong> organic chemistry<br />
which has been so thoroughly investigated in all its details as that <strong>of</strong><br />
the intermediate products which are here involved. The number <strong>of</strong><br />
possible combinations is almost without limit, and we can only refer<br />
to the specialist works, particularly F. Mayer, Chemie der organ.<br />
Farbstqffe, Berlin, 1924 ; Mohlau-Bucherer, Farbenchem. PrakL, Berlin,<br />
1926; Fierz-David, Farbenchemie, Berlin, 1924; Eistenpart, Ghem.<br />
Technol. der organ. Farbst<strong>of</strong>fe, Leipzig, 1925.<br />
The mechanism <strong>of</strong> the coupling reaction has been very exhaustively<br />
studied. Summarising first what has already been mentioned, it must<br />
be noted that the reaction is not confined to the aromatic series, for<br />
diazo-compounds condense also with enols and with the very closely<br />
related aliphatic a,ci-nitro-compounds. The final products <strong>of</strong> these reactions<br />
are not azo-compounds, but the isomeric hydrazones formed from<br />
them by rearrangement.<br />
CH, CH<br />
3<br />
3<br />
KOOC—CH<br />
C—OH<br />
Ethyl acetoacetate<br />
+ H 0 N = N<br />
CH3<br />
C—OH<br />
II<br />
ROOC—C—N=N.C 6H 5<br />
>• CO a-Phenylhydrazone <strong>of</strong> the ester<br />
I <strong>of</strong> a/3-Diketobutyric acid<br />
ROOC—C=N—NH.C RH K<br />
CH2 H O N = N r C H — N = N<br />
II + I —M II I<br />
0=N—OH C6HS Lo=N—OH C6]<br />
aci-nitromethane HC=N—NH.C 6H 5<br />
NO,<br />
Phenylhydrazone <strong>of</strong><br />
nitr<strong>of</strong>ormaldehyde<br />
+ H 2O<br />
Even the doubly unsaturated hydrocarbons, such as butadiene, can<br />
be coupled with suitable diazo-compounds. Finally, not only phenols,<br />
but also phenol ethers, such as anisole, are capable <strong>of</strong> coupling (K. H.<br />
Meyer l ).<br />
1. The simplest theory, developed by K. H. Meyer, traces the ability<br />
to couple to the activity <strong>of</strong> the double bond which adds itself to the<br />
i Annalen, 1913, 398, 66 ; Ber., 1914, 47, 1741.
ANALOGOUS ACTION OF NITKOUS ACID 307<br />
diazohydroxide. By elimination <strong>of</strong> water the azo-compound or phenylhydrazone<br />
is formed.<br />
C = 0<br />
0 H<br />
|| |<br />
|<br />
HC ||<br />
HC—N=N.C6HS<br />
HC—N=N.C6HS C=N—NH.C6H5<br />
HO-N |<br />
|<br />
When the coupling takes place in the y-position the addition correspondingly<br />
occurs in the 1 : 4-positions.<br />
2. Under certain conditions the first products <strong>of</strong> the reaction, in<br />
the case <strong>of</strong> nitrophenols, are diazophenol ethers (diazohydroxy-compounds),<br />
which then very easily undergo rearrangement<br />
N=N0H + HO<br />
•N=N— 0<br />
into the isomeric hydroxyazo-compounds (Dimroth 2 ) just as diazoaminobenzene<br />
changes into y-aminoazobenzene.<br />
3. The compound which couples adds itself to the double bond <strong>of</strong><br />
the diazo-hydroxide either in virtue <strong>of</strong> (a) the mobile hydrogen atom<br />
or (b) the double bond :<br />
(b) 0 -fcLn^^C'xi—0 xl = ^C'Jin<br />
C6H5.N=NOH<br />
"CH2=CH—CH=CH"<br />
\ / I I<br />
H OH<br />
C6H5.N—N<br />
H OHJ<br />
rCH2=CH—CH—CH2 -j<br />
L C.H..N NOHJ<br />
-H.,0<br />
CH2=CH—CH=CH<br />
C6H5.N=N<br />
The method <strong>of</strong> reaction <strong>of</strong> the diazobenzene hydroxide is extraordinarily<br />
similar to that <strong>of</strong> nitrous acid ; practically all substances<br />
which are capable <strong>of</strong> coupling also react with this acid. Comparison<br />
<strong>of</strong> the formulae shows that in the diazo-hydroxide the bivalent radicle<br />
1 Ber., 1907, 40, 2404, 4460 ; 1908, 41, 4012.
308 ANALOGOUS ACTION OF NITKOUS ACID<br />
C6HsN-< takes the place <strong>of</strong> the oxygen atom in nitrous acid. What has<br />
been said <strong>of</strong> the course <strong>of</strong> the coupling reaction can be applied almost<br />
without restriction to the analogous reactions <strong>of</strong> nitrous acid (cf. in this<br />
connection also p. 315). Whereas in coupling it is the phenylazoradicle<br />
that is introduced, in the nitrous acid reactions it is the nitrosogroup<br />
(nitrosophenol, nitrosodimethylaniline) ; whilst the products <strong>of</strong><br />
coupling, e.g. in the case <strong>of</strong> enols, undergo rearrangement to phenylhydrazones,<br />
those from the action <strong>of</strong> nitrous acid change into oximes, e.g.,<br />
KOOC—CH=C—CH3<br />
EOOC—C—CO.CH3<br />
I + 0:N0H —> || +H2O.<br />
OH NOH<br />
Ethyl acetoacetate /so-nitroso-denvative <strong>of</strong> ethyl acetoacetate<br />
Accordingly, diazobenzene and nitrous acid are related to each other<br />
in the same way as are phenylhydrazine and hydroxylamine ; the latter<br />
two substances, in fact, yield the same reaction products with carbonyl<br />
compounds as the former two do with the corresponding methylene<br />
derivatives.<br />
It is consequently intelligible that certain quinones condense with<br />
phenylhydrazine to the same end products as are formed by the coupling<br />
<strong>of</strong> the corresponding phenols with diazobenzene hydroxide (Zincke), e g.,<br />
CO<br />
/3-Naphthoquinone<br />
N-<br />
+ H2N.NH.C6H4 •—' ' n ^ =0<br />
N=N.C6H5<br />
For reasons already frequently mentioned—cf., for example, pp.<br />
106,178,196—the partially hydrogenated aromatic nucleus is not stable;<br />
hence the bracketed intermediate product tends to change into the<br />
" benzenoid " form, while hydrogen wanders from the nitrogen to the<br />
oxygen atom.
CHAPTEK VIII<br />
QUINONOID COMPOUNDS<br />
1. QUINONE FROM ANILINE 1<br />
PROM a tap funnel a solution <strong>of</strong> 30 g. <strong>of</strong> sodium dichromate in 75 c.c.<br />
<strong>of</strong> water is gradually run, with stirring and ice cooling (Fig. 51, p. 146)<br />
into a filter jar containing a solution <strong>of</strong> 23 g. <strong>of</strong> aniline (£ mole) in a<br />
mixture <strong>of</strong> 100 c.c. <strong>of</strong> pure concentrated sulphuric acid and 500 c.c.<br />
<strong>of</strong> water. The temperature should not rise above 10°. The reaction<br />
mixture is then left in a cool place over night and next morning 40 g.<br />
<strong>of</strong> dichromate in 120 c.c. <strong>of</strong> water are added as before. The darkbrown<br />
solution, after standing for a further six hours, is filtered at<br />
the pump through a large Biichner funnel and the solid is washed<br />
with a little water. Then the filtrate is extracted twice, each time<br />
with 0-5 1. <strong>of</strong> ether ; the- ethereal solution is transferred to a distilling<br />
flask suitable for steam distillation and the ether is promptly<br />
distilled. The distilled ether, divided into two portions, is used to<br />
extract the reaction mixture again and the solvent is again removed<br />
from the extracts by distillation. 2 The residual crude quinone, to<br />
which the material on the funnel and the filter paper are added, is<br />
subjected directly to steam distillation, which drives the quinone<br />
into the receiver as magnificent golden-yellow crystals. Yield<br />
14-16 g. These are dried, first for a short time between filter paper,<br />
and then in a non-evacuated desiccator over calcium chloride.<br />
Melting point 116°. On account <strong>of</strong> its great volatility it may not<br />
be kept for any length <strong>of</strong> time exposed to the air. (Test a sample.)<br />
Alcohol or petrol ether may be used for recrystallisation. The pure<br />
dry compound can be preserved for a long time.<br />
1 Annakn, 1838, 27, 268 ; 1842, 45, 354 ; 1882, 215, 125. Ber., 1886, 19, 1467 ;<br />
1887, 20, 2283.<br />
2 The distilled ether, which is yellow because quinone volatilises with it, can<br />
be made fit for other use by shaking with dilute alkali hydroxide solution which<br />
removes the quinone in the form <strong>of</strong> the dark brown " humic acid " salt.<br />
309
310 QUINONB FKOM ANILINE<br />
y-Benzoquinone, commonly called simply quinone, is one <strong>of</strong> the<br />
most interesting <strong>of</strong> organic compounds, and is remarkable because <strong>of</strong><br />
its colour, odour, and volatility. The steam distillation always involves<br />
not inconsiderable decomposition.<br />
Quinone is produced in small yield by direct oxidation <strong>of</strong> benzene<br />
itself with silver peroxide, but better by the action <strong>of</strong> oxidising agents<br />
on a large number <strong>of</strong> its y-disubstitution products. Thus, in addition<br />
to quinol, p-aminophenol (experiment, p. 176), y-anisidine, y-toluidine,<br />
and sulphanilic acid as well as y-phenylenediamine and many <strong>of</strong> its<br />
derivatives yield quinone in this way.<br />
More easily than benzene, naphthalene can be oxidised directly to<br />
(a)-quinone; this is the preparative method with anthracene and phenanthrene.<br />
Although quinone is a derivative <strong>of</strong> dihydrobenzene and therefore<br />
not genuinely " aromatic ", its formation from a suitable precursor is<br />
favoured whenever an oxidising agent gives out energy.<br />
The reactions <strong>of</strong> quinone consist essentially <strong>of</strong> various types <strong>of</strong><br />
addition to the double bonds present in the molecule. This addition<br />
takes place :<br />
(1) at the G=C-double bond.-—Production <strong>of</strong> di- and tetra-bromides<br />
<strong>of</strong> quinone;<br />
(2) in the Impositions at the two oxygen atoms.—Addition <strong>of</strong> hydrogen<br />
to form quinol. The affinity in this reaction is so great that even<br />
aqueous sulphurous acid suffices for hydrogenation. (Experiment.)<br />
The dehydrogenation <strong>of</strong> quinol to quinone constitutes<br />
the converse process, an elimination from the Impositions ;<br />
(3) in the 1 : ^-positions at oxygen and carbon simultaneously;<br />
derivatives <strong>of</strong> quinol are formed.<br />
OH ~ OH<br />
+ HE —><br />
JHE -R<br />
To this scheme most <strong>of</strong> the reactions <strong>of</strong> quinone conform, and all those<br />
which are <strong>of</strong> most importance, e.g. the addition <strong>of</strong> HC1, HCN, amines,<br />
thiophenol, thiosulphuric acid, acid chlorides, and acid anhydrides.<br />
As an example the reaction with aniline may be selected. In<br />
accordance with the scheme formulated, the first reaction product<br />
obtained is anilinoquinol (R =NH.C8H5). The reaction does not<br />
stop at this stage, however. Between this first reaction product and<br />
unchanged quinone still present there promptly occurs a reciprocal<br />
hydrogenation and dehydrogenation characteristic <strong>of</strong> very many <strong>of</strong><br />
the reactions <strong>of</strong> quinone.
ANILINOQUINONE<br />
0 0<br />
The great affinity <strong>of</strong> quinone for hydrogen leads to the formation <strong>of</strong><br />
anilinoquinone which can now, in the same way, add a further equivalent<br />
<strong>of</strong> aniline to the half <strong>of</strong> the molecule not yet involved. The dianilinoquinol<br />
is converted into dianilinoquinone in the same way as the first<br />
reaction product was changed. (Write the equation.)<br />
Experiments—Quinol from Quinone. Suspend about 2 g. <strong>of</strong><br />
quinone in 50 c.c. <strong>of</strong> water and while shaking frequently saturate the<br />
suspension with sulphur dioxide. Keep for some time and then<br />
extract the now colourless liquid twice with ether, dry the ethereal<br />
extract with calcium chloride, and evaporate the ether. The residue<br />
<strong>of</strong> quinol crystallises. Kecrystallise it from a little water. Melting<br />
point 169°. Warm a sample with dilute sulphuric acid and a few<br />
drops <strong>of</strong> dichromate solution ; the odour <strong>of</strong> quinone is emitted.<br />
Experiments—Anilinoquinone. 1 Dissolve 4 g. <strong>of</strong> quinone in 400<br />
c.c. <strong>of</strong> water. Cool the solution and add 1-72 g. <strong>of</strong> aniline dissolved<br />
in 10 c.c. <strong>of</strong> 20 per cent acetic acid. Leave the mixture in the cold<br />
for three hours with frequent shaking, then collect the reddishbrown<br />
crystalline precipitate at the pump, dry it in vacuo, and free it<br />
from the monoanilino-compound by repeated careful boiling with<br />
petrol ether (boiling point 80°-90°). From the petrol ether this<br />
compound separates on cooling in the form <strong>of</strong> small golden-brown<br />
needles. Melting point 119°. The insoluble portion consists <strong>of</strong><br />
dianilinoquinone.<br />
On the Formation <strong>of</strong> Quinone from Aniline.-—The greenish-black<br />
intermediate product which is observed during the preparation <strong>of</strong><br />
quinone is aniline black. This fact already shows that the conversion <strong>of</strong><br />
aniline into quinone does not consist simply in the introduction <strong>of</strong> oxygen<br />
and elimination <strong>of</strong> nitrogen as the simplest equation would indicate.<br />
Quinone is rather the end-product <strong>of</strong> a whole series <strong>of</strong> complicated<br />
processes and is formed, as we shall show, by alternate dehydrogenation<br />
and hydrolysis (Willstatter 2 ). Consequently, the NH2-group <strong>of</strong> the<br />
aniline appears in the end-product as ammonia. That this is so can<br />
easily be shown by expelling dissolved ether from a little <strong>of</strong> the extracted<br />
1 H. and W. Suida, Annalen, 1918, 416, 118.<br />
2 Ber., 1907, 40, 2665 ; 1909, 42, 2147.<br />
0
312 MECHANISM OF QUINONB FOKMATION<br />
solution on the water bath, and then testing in the usual way for<br />
ammonia. It is probable that each time the aniline is dehydrogenated<br />
the first compound formed is the very unstable radicle-like nitrogenfhenyl<br />
(Bambergei, 8. Goldschmidt).<br />
C6HS.NH2 _l!^ C6H5N
2H '°> O=/~\=O + NH3 + H2N<br />
QUINONBS 313<br />
This phase <strong>of</strong> the whole process takes place slowly, and that is why<br />
the oxidation solution must be kept for a long time.<br />
If this cleavage principle is applied to the molecule <strong>of</strong> aniline black<br />
it will be found that from it four molecules <strong>of</strong> quinone, three molecules<br />
<strong>of</strong> y-phenylenediamine, and one molecule each <strong>of</strong> aniline and ammonia<br />
arise. Since an excess <strong>of</strong> chromic acid is present, the y-phenylenediamine<br />
is readily dehydrogenated to quinonediimine, which is hydrolytically<br />
decomposed into quinone and ammonia. The single molecule<br />
<strong>of</strong> aniline begins the cycle anew.<br />
Aniline black is also an important fast dye for cotton and is produced<br />
on the fibre at a high temperature (by " steaming ") from an<br />
aniline salt (hydrochloride) and an oxidising agent. It is not probable<br />
that the two kinds <strong>of</strong> this dye which are known have the same constitution,<br />
for they have different degrees <strong>of</strong> stability towards acid;<br />
technical aniline black probably contains phenazine ring systems<br />
(Bucherer, Green).<br />
The oxidation <strong>of</strong> aniline by Caro's acid to nitrosobenzene, which<br />
proceeds in a quite different way, may be recalled here (p. 179).<br />
Other Quinones.—Look up o-quinones and the three naphthoquinones<br />
; the best method <strong>of</strong> preparing a- and j8-naphthoquinone is<br />
froml : 4-andl : 2-aminonaphthol respectively, which are obtained from<br />
azo-dyes <strong>of</strong> the two naphthols by reduction (see p. 302).<br />
Experiment. Quantitative Determination <strong>of</strong> Quinone. 2 -—Add<br />
10 c.c. <strong>of</strong> a 10 per cent potassium iodide solution and 10 c.c. <strong>of</strong><br />
2 iV-sulphuric acid to 20 c.c. <strong>of</strong> the aqueous mother liquors from<br />
which the quinone has been filtered and immediately titrate the<br />
iodine which is liberated with 0-1 iV-thiosulphate solution. One c.c.<br />
<strong>of</strong> thiosulphate solution =0-0054 g. <strong>of</strong> quinone.<br />
A more accurate method is given by Willstatter and Majima,<br />
Ber., 1910, 43, 1171.<br />
Experiment.-—Pour 1 c.c. <strong>of</strong> dilute sodium hydroxide solution<br />
into a test tube containing a small amount <strong>of</strong> quinone. The substance<br />
dissolves with production <strong>of</strong> a deep brown colour. Acidify<br />
the alkaline solution. Amorphous brown flakes are precipitated.<br />
Quinone is very sensitive to alkalis, even to carbonate and ammonia,<br />
and is converted by them into a brown acid possibly identical with the<br />
natural humic acid <strong>of</strong> brown coal (lignite) (Eller). The mechanism <strong>of</strong><br />
this reaction remains obscure.<br />
l A. Valeur, Compt. rend., 1899, 129, 552.
314 ^-NITKOSODIMETHYLANILINE<br />
Experiment.-—On a small hand balance, having two sheets <strong>of</strong><br />
paper counterpoised in the pans, weigh out equal quantities (about<br />
0-5 g,) <strong>of</strong> quinone and quinol; dissolve the two substances separately<br />
in warm water and mix the solutions. Magnificent green needles <strong>of</strong><br />
quinhydrone crystallise almost at once. After some time collect<br />
them at the pump, wash with water, and dry between filter papers<br />
over calcium chloride in a non-evacuated desiccator. Boil a few <strong>of</strong><br />
the crystals with water and smell the vapours.<br />
The combination <strong>of</strong> quinones and quinols in solution or when molten<br />
to form the deeply coloured quinhydrones is quite general. Other<br />
components <strong>of</strong> different origin, such as y-phenylenediamine and even<br />
quinol ethers, also take part in this remarkable union. The molecular<br />
proportions may also be other than 1:1. In general the quinhydrones<br />
only exist as such in the crystalline state : in solution they are to a very<br />
great extent dissociated into their constituents. Consequently they<br />
have no special reactions <strong>of</strong> their own, but react like a mixture <strong>of</strong> quinone<br />
and hydro-compound. Thus the simple quinhydrone is converted by<br />
oxidising agents into quinone, by reducing agents into quinol.<br />
This labile behaviour <strong>of</strong> the quinhydrones has led to the view that<br />
in them the molecules are held together, not by normal, but by secondary<br />
valencies. The most interesting point about the quinhydrones js the<br />
deepening <strong>of</strong> colour which accompanies their formation. An explanation<br />
<strong>of</strong> this deepening may be found in the simultaneous presence <strong>of</strong> a<br />
quinonoid and a benzenoid ring in the same molecule. (An analogous<br />
bathychromic action caused by different stages <strong>of</strong> oxidation is encountered<br />
in the case <strong>of</strong> Prussian blue.)<br />
2. 2>-NITROSODIMETHYLANILINE 1<br />
Dimethylaniline (40 g.; 0-33 mole) is dissolved in 250 c.c. <strong>of</strong><br />
approximately 5 iV-hydrochloric acid (one part <strong>of</strong> concentrated acid<br />
and one part <strong>of</strong> water) in a filter jar (capacity 1 1.) The jar is immersed<br />
in ice; 200 g. <strong>of</strong> ice are dropped in, and then with good<br />
stirring-—preferably with a mechanical stirrer-—a cold solution <strong>of</strong><br />
25 g. <strong>of</strong> sodium nitrite in 100 c.c. <strong>of</strong> water is run in gradually from a<br />
dropping funnel (Fig. 51, p. 146). The temperature should not rise<br />
above 5° and no nitrous gases should be evolved. After the mixture<br />
has stood for one hour the orange-yellow hydrochloride is filtered<br />
thoroughly at the pump and washed several times with dilute hydrochloric<br />
acid (say 2 N). The salt is sufficiently pure for subsequent<br />
1 Baeyer and Caro, Bar., 1874, 7, 810, 963.
^-NITKOSOBASES AND THBIK SALTS 315<br />
reduction and for the preparation <strong>of</strong> dimeihylamine. A few grammes<br />
may be recrystallised from dilute hydrochloric acid, without heating<br />
to the boiling point, however.<br />
Since it is best to use the moist preparation for the further experiments,<br />
the whole <strong>of</strong> the material is weighed and an aliquot<br />
portion is dried, first on porous plate and then in a vacuum desiccator<br />
or else on the water bath, so that the yield can be determined.<br />
It amounts to over 90 per cent <strong>of</strong> the theoretical.<br />
The free base is obtained by rubbing the moist salt (5-10 g.) under<br />
sodium carbonate solution in a separating funnel and shaking with<br />
ether until the whole is dissolved. The beautiful emerald green<br />
solution is first concentrated on the water bath and then the solvent<br />
is allowed to evaporate from a flat dish exposed to the air. Large<br />
green plates <strong>of</strong> nitrosodimethylaniline remain. They melt at 80° and<br />
can be recrystallised from petrol ether (boiling point 60°-80°).<br />
The tertiary aromatic bases share with the phenols the property <strong>of</strong><br />
taking up a nitroso-group in the y-position when treated with nitrous<br />
acid in acid solution. As was mentioned elsewhere (p. 307), this reaction<br />
may be compared to the coupling <strong>of</strong> these compounds with diazobenzene.<br />
Secondary amines such as methylaniline and diphenylamine also<br />
form nitrosamines very rapidly. By means <strong>of</strong> gaseous hydrochloric acid<br />
in anhydrous solvents they undergo rearrangement to the isomeric<br />
y-nitroso-bases.<br />
•NH—( > + HONO —><br />
-N—< V-NO.<br />
H v-/<br />
y-Nitrosodiphenylamine<br />
In contradistinction to nitrosobenzene these bases, and y-nitrosodimethylaniline<br />
also, exist only in the unimolecular green form.<br />
The salts <strong>of</strong> y-nitrosodimethylaniline, on the other hand, are yellow.<br />
Moreover, since they are neutral-—test this with the pure salt—and<br />
since dimethylaniline hydrochloride is acid to litmus paper, they cannot<br />
have resulted from the simple addition <strong>of</strong> the acid to the tertiary<br />
dimethylamino-group. It is therefore assumed that the salts are formed<br />
by the addition <strong>of</strong> H and acid ion in the 1 : 7-positions, so that a<br />
quinonoid system results through a rearrangement:<br />
NO
316 HYDROLYSIS OF ^-NITROSODIMBTHYLANILINB<br />
»HON= ^-CH3.<br />
\ci<br />
By addition <strong>of</strong> methyl iodide there is likewise formed a yellow<br />
quinonoid salt (having the H3CON=group) the constitution <strong>of</strong> which<br />
can be deduced with some degree <strong>of</strong> probability from the fact that the<br />
basic group is eliminated by alkalis not as trimethylamine but as<br />
dimethylamine.<br />
DlMETHYLAMINE AND ^-NITROSOPHENOL FROM<br />
^-NlTROSODIMETHYLANILINE<br />
A solution <strong>of</strong> 25 g. <strong>of</strong> sodium hydroxide in 500 c.c. <strong>of</strong> water is<br />
heated to boiling (porous pot!) in a distilling flask (capacity 1 1.)<br />
connected to a downward condenser which is provided with a receiver<br />
containing 60 c.c. <strong>of</strong> 2 i^-hydrochloric acid. Through the<br />
corked neck <strong>of</strong> the flask 18-6 g. <strong>of</strong> nitrosodimethylaniline hydrochloride—preferably<br />
the moist reaction product—are added in<br />
portions. Bach addition is only made after most <strong>of</strong> the oily drops<br />
<strong>of</strong> the base from the preceding portion have dissolved, and finally<br />
the liquid is boiled until it has become reddish-brown. The dimethylamine<br />
produced is trapped in the hydrochloric acid in the<br />
receiver : at the conclusion <strong>of</strong> the distillation the contents <strong>of</strong> the<br />
receiver must still be acid. They are evaporated to dryness on the<br />
water bath in a small porcelain or glass basin, and finally the completely<br />
anhydrous salt can be recrystallised from a very small<br />
amount <strong>of</strong> absolute alcohol. Yield 5-6 g.<br />
The nitrosophenol is precipitated from the cooled aqueous solution<br />
by acidification with dilute sulphuric acid and is extracted with<br />
ether in a separating funnel. After brief drying over calcium<br />
chloride the brownish-green solution is concentrated on the water<br />
bath. The sparingly soluble compound crystallises from the ether<br />
on cooling. Melting point 120°-130° (decomp.). Complete purification<br />
<strong>of</strong> nitrosophenol is difficult.<br />
The nitroso-group in the y-position has a remarkable influence in<br />
making possible the hydrolytic removal <strong>of</strong> the dimethylamino group<br />
from the benzene ring. The reaction is used technically for the preparation<br />
<strong>of</strong> secondary amines. (Trimethylamine is obtained by heating<br />
ammonium chloride with formaldehyde.)<br />
The tautomeric quinonoid formula O=\ %=N0H <strong>of</strong> quinone
DETECTION OF NITKOSO-GKOUPS 317<br />
monoxime is also considered for y-nitrosophenol, although its whole<br />
chemical behaviour is in complete agreement with the phenolic structure.<br />
Like nitrosobenzene, nitrosophenol, when quite pure, is (very<br />
nearly) colourless and the solutions are olive-green. This would not<br />
be expected from the quinonoid formula.<br />
The Liebermann Reaction.—Dissolve a small amount <strong>of</strong> nitrosophenol<br />
in a little molten phenol and add concentrated sulphuric acid.<br />
A magnificent cherry-red colour is obtained: when the melt is<br />
diluted with water and alkali is added the colour changes to blue.<br />
Since phenol is converted to nitrosophenol by nitrous acid, even<br />
when the latter is combined in the form <strong>of</strong> the NO-group, labile nitrosogroups<br />
may be detected by the Liebermann reaction.<br />
3. p-AMINODIMETHYLANILINE<br />
In a short-necked, round bottomed flask (capacity 500 c.c.) 100 g.<br />
<strong>of</strong> stannous chloride are dissolved in 120 c.c. <strong>of</strong> concentrated hydrochloric<br />
acid, and 38 g. (0'2 mole) <strong>of</strong> the crude moist nitrosodimethylaniline<br />
hydrochloride are gradually added in small portions with<br />
vigorous stirring or shaking. If the reaction does not set in at once<br />
the flask is warmed on the water bath ; after a short time the salt<br />
which has been added should go completely into solution. The reaction<br />
must be so regulated that it goes on continuously without<br />
becoming altogether too violent.<br />
At the end, the solution, which has become pale yellow, is cooled<br />
externally and internally (drop in some ice) and made alkaline with<br />
a solution <strong>of</strong> 150 g. <strong>of</strong> commercial sodium hydroxide in 300 c.c. <strong>of</strong><br />
water ; 1 most <strong>of</strong> the stannic acid which is at first precipitated goes<br />
into solution. The oily base set free is taken up in ether (irrespective<br />
1 The electrolytic separation <strong>of</strong> the tin is much more elegant. In cases where the<br />
reduction product cannot be extracted as base from the alkaline solution (aminoalcohols,<br />
amino-acids, and the like) this method is much to be preferred to the precipitation<br />
with hydrogen sulphide, and in the present case also it is to be highly<br />
recommended, if only for what it teaches.<br />
The electrolysis is carried out in a medium-sized filter jar; two moderately<br />
thick carbon rods serve as electrodes. The cathode dips into the solution, the<br />
anode into 2i^-sulphuric acid contained in a small porous cell, which also dips into<br />
the liquid. The electrodes are fixed a short distance apart and the current is<br />
obtained from two units, arranged in series, <strong>of</strong> an accumulator battery <strong>of</strong> the usual<br />
capacity. At a potential difference <strong>of</strong> 4 volts 1-5—2 amperes pass through the<br />
solution.<br />
Application <strong>of</strong> Faraday's Law <strong>of</strong> Electrochemical Equivalents.—1 equivalent <strong>of</strong><br />
1 "I Q Oft Kf\f\<br />
g n + + + + _ o r 29.5 g. requires ? • = 2 6 * 8 a m p e r e h o u r s ; w i t h a current <strong>of</strong> 2<br />
4 ouOO
318 ^-AMINODIMETHYLANILINE<br />
<strong>of</strong> small amounts <strong>of</strong> undissolved stannic acid), the liquid is extracted<br />
once or twice more with ether, the ether is evaporated after drying<br />
for a short time over fused potassium carbonate, and the free base is<br />
at once distilled in a vacuum. It passes over as an almost colourless<br />
liquid at 138 o -140°/12 mm. Yield 18-20 g. (about 75 per cent).<br />
It solidifies on cooling. Melting point 41°. The free amine is<br />
unusually sensitive towards air. Already after a few hours the<br />
initially colourless preparation becomes brown. It can be preserved<br />
for some weeks if sealed in an atmosphere <strong>of</strong> nitrogen, but<br />
in air it can hardly be kept for a day. Its salts, on the other hand,<br />
are stable.<br />
Hydrochloride.—A solution <strong>of</strong> the base in a small excess <strong>of</strong><br />
hydrochloric acid (equal volumes <strong>of</strong> the concentrated 7 iV-acid and<br />
water) may be evaporated in a porcelain basin on the water bath,<br />
and the residue may be dried completely in a vacuum desiccator over<br />
sulphuric acid and solid potassium hydroxide.<br />
An almost general and very elegant way <strong>of</strong> obtaining the hydrochlorides<br />
<strong>of</strong> organic amines consists in neutralising them (until acid<br />
to Congo paper) with alcoholic hydrogen chloride and then gradually<br />
adding absolute ether with rubbing until precipitation <strong>of</strong> the salt<br />
takes place. Care must be taken not to precipitate the salt in an<br />
amorphous condition by too rapid addition <strong>of</strong> the ether. It is best<br />
to wait for the beginning <strong>of</strong> crystallisation, which usually shows itself<br />
by the appearance <strong>of</strong> a powdery coating on the places rubbed by<br />
the glass rod.<br />
The base is acetylated by adding to it an equal weight <strong>of</strong> acetic<br />
anhydride, heating for a short time on the water bath, and then<br />
diluting with water. In order to isolate the still basic acetylcompound<br />
the free acetic acid is just neutralised with sodium<br />
hydroxide. Melting point <strong>of</strong> the substance after recrystallisation<br />
from water 130°.<br />
The diamine <strong>of</strong> which the preparation has just been described is <strong>of</strong><br />
great importance from several points <strong>of</strong> view. The reactions concerned<br />
depend on the change which its salts undergo on oxidation, and therefore<br />
this change will be considered first.<br />
Experiment.-—Dissolve a few granules <strong>of</strong> the freshly prepared<br />
amperes, therefore, 13-4 hours.<br />
Since, when the concentration <strong>of</strong> tin ions decreases, hydrogen is also evolved,<br />
the electrolysis lasts somewhat longer than the calculated time, but can perfectly<br />
well be allowed to proceed over night.
QUINONBDIIMINBS 319<br />
base (or <strong>of</strong> a salt) in a few drops <strong>of</strong> dilute acetic acid in a test tube<br />
and add, first, about 5 c.c. <strong>of</strong> water and a few small pieces <strong>of</strong> ice, and<br />
then a few drops <strong>of</strong> very dilute bromine water or a dichromate<br />
solution. A magnificent red colour appears. If somewhat more<br />
concentrated solutions are used and the oxidising solution is heated<br />
to boiling, the odour <strong>of</strong> quinone is perceived.<br />
The typical transformation <strong>of</strong> all y-phenylenediamine derivatives<br />
by oxidising agents in acid solution consists in a change into a salt <strong>of</strong><br />
the quinonediimine series. The dye just observed, so called "Wurster's<br />
red ", was long regarded as a simple quinonimonium salt:<br />
This, however, already appeared improbable when the (colourless)<br />
chloride <strong>of</strong> the simple quinonediimine became known (Willstatter).<br />
Quinonediimine and its derivatives are reconverted by reducing<br />
agents into the corresponding phenylenediamines. It has been found<br />
that for the formation <strong>of</strong> Wurster's red the amount <strong>of</strong> oxidising agent<br />
required is equivalent to one, not to two H-atoms. Accordingly the<br />
reduction equivalent, which can be determined by titration with<br />
standard solution <strong>of</strong> stannous chloride, is also only half as great as was<br />
previously supposed. If a weighed amount <strong>of</strong> y-aminodimethylaniline<br />
salt is oxidised with dilute bromine solution <strong>of</strong> known titre, the point<br />
<strong>of</strong> maximum production <strong>of</strong> dye is reached when one equivalent <strong>of</strong><br />
bromine has reacted with one mole <strong>of</strong> salt. If a second equivalent <strong>of</strong><br />
bromine is added, the colour tone diminishes to yellow.<br />
At this point the oxidation stage <strong>of</strong> quinonediimine has been fully<br />
reached ; its (very unstable) salts have scarcely any colour. The production<br />
<strong>of</strong> colour only takes place when quinonoid and benzenoid systems<br />
are present together. The molecular union <strong>of</strong> the two substances at<br />
different stages <strong>of</strong> oxidation produces the intense absorption which is a<br />
prerequisite for the formation <strong>of</strong> a dye (Willstatter and Piccard). This<br />
union need not take place in the proportion 1:1, which obtains in the<br />
present case. The relations between quinhydrone and quinone-quinol<br />
are quite similar (p. 314).<br />
In both cases the linkage between the molecules is labile and does<br />
not involve normal valencies. In general, " molecular compounds "<br />
are considered to be systems which are held together by the excess<br />
residual affinities <strong>of</strong> the components, by the mutual attraction <strong>of</strong> the<br />
molecular fields <strong>of</strong> force.<br />
Willstatter's theory covers not only the class <strong>of</strong> intermolecular<br />
partially quinonoid (meriquinonoid) salts ; it also provides a satisfactory<br />
conception <strong>of</strong> the true quinonoid dyes. The same principle, ex-
320 WUKSTEK'S BED<br />
pressed intramolecularly, is encountered throughout, i.e. the two systems<br />
which are at difEerent stages <strong>of</strong> oxidation (benzenoid and quinonoid) are<br />
here present in the same molecule. These relations are very clearly<br />
illustrated by parafuchsine.<br />
If we remove the NH2-group from one benzene ring the resulting<br />
substance, " Doebner's violet", still has the character <strong>of</strong> a dye, since<br />
the above-mentioned conditions are still satisfied. But if the NH2 is<br />
also lacking in the second benzene ring there results, as it were, a completely<br />
quinonoid (holoquinonoid) salt which, as we saw in the example<br />
from which we started, is no longer a dye. The tinctorial properties<br />
<strong>of</strong> the other quinonoid dyes, such as the indamines, safranines, methylene<br />
blue, etc., are to be explained in the same way. It is absolutely<br />
necessary to become familiar with the basis <strong>of</strong> this important theory<br />
through the following experiment.<br />
Experiments—Dissolve 1 -3 g. <strong>of</strong> freshly prepared diamine base in<br />
2 c.c. <strong>of</strong> glacial acetic acid which has been diluted with 10 c.c. <strong>of</strong><br />
water and make the volume <strong>of</strong> the solution up to 95 c.c. in a measuring<br />
cylinder. Take 5 c.c. <strong>of</strong> this 0-1 i\f-solution in a conical flask<br />
(capacity 500 c.c.) and dilute further with 45 c.c. <strong>of</strong> ice-water.<br />
Before preparing the solution <strong>of</strong> the base, fill one burette with<br />
bromine solution (16 c.c. <strong>of</strong> saturated bromine water diluted with<br />
280c.c. <strong>of</strong> ice water) and another with approximately 0-02iV-stannous<br />
chloride solution, freshly prepared by dissolving 0-8 g. <strong>of</strong> tinfoil 1 or <strong>of</strong><br />
thinly granulated tin in 4 c.c. <strong>of</strong> hydrochloric acid(l: 1), and diluting<br />
to 500 c.c. with water which has previously been boiled.<br />
Now keep the solution <strong>of</strong> the base cool in ice and rapidly run in<br />
bromine solution with continuous shaking. Observe that the fine<br />
red colour attains its maximum when about 25 c.c. <strong>of</strong> the bromine<br />
solution have been added, but that after the addition <strong>of</strong> 25 c.c. more<br />
the colour becomes much lighter. Because <strong>of</strong> secondary reactions a<br />
pure yellow colour is never produced ; as a rule, yet a little more<br />
bromine must be added rapidly. When the loss <strong>of</strong> colour has ceased<br />
run in stannous chloride solution immediately. After 25 c.c. have<br />
been added the beautiful colour <strong>of</strong> Wurster's red returns, only to<br />
1 Bear in mind that present-day " tinfoil " ia almost always aluminium.
BINDSCHBDLBK'S GKEBN 321<br />
disappear again on further reduction. The dye is also reformed by<br />
adding 5 c.c. <strong>of</strong> the original solution <strong>of</strong> the diamine salt.<br />
Because <strong>of</strong> the great instability <strong>of</strong> the quinonoid salts it is necessary<br />
to work rapidly, using greatly diluted and cool solutions.<br />
The y-quinonediimines are the parent substances <strong>of</strong> the indamine<br />
dyes and <strong>of</strong> the tricyclic quinonoid salts <strong>of</strong> the phenazine, phenthiazine,<br />
and phenoxazine groups which are related to them. (Detailed information<br />
on this subject is to be found in special works, e.g. <strong>of</strong> Nietzki-<br />
Mayer and <strong>of</strong> Bucherer.)<br />
Let us consider the process <strong>of</strong> indamine formation, taking our quinonediimine<br />
base as the starting point. In accordance with a general<br />
addition reaction which is characteristic <strong>of</strong> all quinonediimines and also<br />
plays a part in the formation <strong>of</strong> aniline black from aniline (cf. p. 312),<br />
the dimethylquinonediimonium salt is capable <strong>of</strong> combining with great<br />
ease with one molecule <strong>of</strong> aniline or dimethylaniline :<br />
>N(CH3)2<br />
>N(CH3)2.<br />
The new y-phenylenediamine derivative so formed is further dehydrogenated<br />
to a quinonoid indamine dye :<br />
the constitution <strong>of</strong> which is in complete accord with Willstatter's theory.<br />
This dye, known as " Bindschedler's green ", is <strong>of</strong> no practical importance<br />
since, like all indamines, it is easily hydrolysed, especially by acids :<br />
Preparation <strong>of</strong> Bindschedler's Green. 1 —Dimethyl-^-phenylenediamine<br />
(7 g.) and dimethylaniline (6 g.) are dissolved in a mixture <strong>of</strong><br />
40 c.c. <strong>of</strong> concentrated hydrochloric acid and 40 c.c. <strong>of</strong> water. Into<br />
the solution, which is kept cool in ice and is stirred mechanically or<br />
1 Ber., 1883, 16, 464, 868 ; 1915, 48, 1087.
322 MBTHYLBNB BLUB<br />
with a glass rod, a solution <strong>of</strong> 10 g. <strong>of</strong> sodium dichromate in 20 c.c. <strong>of</strong><br />
water is slowly run from a dropping funnel. Zinc chloride solution<br />
(10 g. <strong>of</strong> salt in 20 c.c. <strong>of</strong> water) is now added and, especially on<br />
scratching, the beautiful zinc double salt <strong>of</strong> the dye crystallises.<br />
After half an hour it is collected at the pump and washed successively<br />
with cold water, alcohol, and ether. Yield 10-12 g. If well<br />
dried the dye can be preserved for a long time.<br />
2-3 g. are placed in a distilling flask, along with 20 c.c. <strong>of</strong> 2 Nhydrochloric<br />
acid, and distilled with steam through a water-cooled<br />
condenser. Characteristic yellow needles <strong>of</strong> quinone soon pass over.<br />
METHYLENE BLUE<br />
If the oxidation which leads to the formation <strong>of</strong> " Bindschedler's<br />
green " takes place in the presence <strong>of</strong> hydrogen sulphide the process is<br />
varied by the entrance <strong>of</strong> sulphur. In principle, however, the mechanism<br />
is the same as before. The following formulae show that an addition<br />
<strong>of</strong> H—SH and a subsequent intramolecular addition <strong>of</strong> a mercaptan<br />
group are stages in the reaction :<br />
(H3C)2N:<br />
Cl<br />
^ /<br />
(H3C)2N/ V \SH ^/ X N(CH3)2<br />
Cl<br />
(<br />
Cl<br />
N(CH3)2<br />
Cl<br />
NH2
VI<br />
MBTHYLBNE BLUB 323<br />
Methylene blue is also produced by the oxidation <strong>of</strong> dimethyl-yphenylenediamine<br />
without the addition <strong>of</strong> dimethylaniline, and was<br />
discovered in this way by Caro in 1876. In explanation <strong>of</strong> this modification<br />
it is considered that the intermediate product (not isolated)<br />
at stage II is probably converted into the substance IV, in which<br />
the other ring is quinonoid, by replacement <strong>of</strong> the NH-group by<br />
=N/~V-N(CH 3) 2. The NH-group is eliminated as NH3. All ex-<br />
perience indicates that quinonoid linkages easily shift from one ring<br />
to another.<br />
Bernthsen, 1 whose brilliant work elucidated the constitution <strong>of</strong> the<br />
dye, suggested a technical process in which, at stage I, thiosulphuric<br />
acid is added; its sulpho-group is eliminated as sulphuric acid in the<br />
course <strong>of</strong> the process.<br />
Dimethyl-^-phenylenediamine (7-6 g.) is dissolved in 70 c.c. <strong>of</strong><br />
iV-hydrochloric acid, and 35 g. <strong>of</strong> zinc chloride in 50 c.c. <strong>of</strong> water are<br />
added. With good stirring 12 g. <strong>of</strong> aluminium sulphate in 20 c.c. <strong>of</strong><br />
water and then 15 g. <strong>of</strong> sodium thiosulphate in 20 c.c. <strong>of</strong> water are<br />
poured in. To the solution thus obtained one-third <strong>of</strong> a solution <strong>of</strong><br />
16 g. <strong>of</strong> sodium dichromate in 30 c.c. <strong>of</strong> water is at once added and<br />
the temperature <strong>of</strong> the solution is raised as rapidly as possible to<br />
40°. The addition <strong>of</strong> 6 g. <strong>of</strong> dimethylaniline dissolved in 8 c.c. <strong>of</strong><br />
concentrated hydrochloric acid follows, and finally the remainder <strong>of</strong><br />
the oxidising agent is poured in. Of course, all these solutions are<br />
prepared before the experiment is begun.<br />
The temperature <strong>of</strong> the liquid is now raised, first quickly to 70°<br />
and then slowly to 85° ; this causes precipitation <strong>of</strong> the dye. After<br />
a quarter <strong>of</strong> an hour the mixture is cooled to 50° ; precipitated inorganic<br />
material is dissolved by adding 15 c.c. <strong>of</strong> concentrated<br />
sulphuric acid and, when the mixture has been cooled completely,<br />
the crude dye is filtered as dry as possible at the pump. The product<br />
is at once dissolved in 200-300 c.c. <strong>of</strong> boiling water ; the solution is<br />
filtered and left to crystallise over night after 20 g. <strong>of</strong> concentrated<br />
zinc chloride solution (1:1) and 40 g. <strong>of</strong> finely powdered common salt<br />
have been added. The beautiful crystals, which have a red lustre,<br />
1 A. Bernthsen, Annalen, 1885, 230, 73; 1889, 251, 1 ; see especially pp. 49,<br />
69, 79 ; Fierz-David, Farbenchemie, 2nd Ed., 1922, p. 186.
324 MALACHITE GKBEN<br />
are filtered as dry as possible at the pump and washed twice with a<br />
little ice-cold water. Yield 10-12 g.<br />
The aqueous solution <strong>of</strong> methylene blue is not decolorised by sodium<br />
hydroxide ; the blue water-soluble ammonium base is formed. The dye<br />
is converted by reducing agents into the easily oxidisable leuco-base.<br />
The following experiment, which demonstrates the formation <strong>of</strong> methylene<br />
blue by the introduction <strong>of</strong> sulphur between the rings <strong>of</strong> Bindschedler's<br />
green, is very instructive.<br />
Experiment.-—Pass hydrogen sulphide slowly into the most<br />
concentrated aqueous solution <strong>of</strong> Bindschedler's green obtainable,<br />
until after some time the colour has changed to yellowish-red. Now<br />
add dilute hydrochloric acid and the solution <strong>of</strong> 0-3 g. <strong>of</strong> sodium<br />
dichromate. Precipitate the methylene blue formed by adding zinc<br />
chloride solution.<br />
4. BASIC TRIPHENYLMETHANE DYES<br />
MALACHITE GREEN FROM BENZALDEHYDE AND<br />
DlMETHYLANILINE 1<br />
Preparation <strong>of</strong> the Leuco-Base.—Zinc chloride (10 g.) is fused in a<br />
porcelain basin, cooled, and powdered. It is then added to a mixture<br />
<strong>of</strong> 25 g. <strong>of</strong> dimethylaniline and 10 g. <strong>of</strong> benzaldehyde (both freshly<br />
distilled) and the whole is heated in a porcelain basin on the water<br />
bath with frequent stirring for four hours. By the addition <strong>of</strong> hot<br />
water the viscous mass is liquefied on the water bath and the hot<br />
liquid is poured into a half-litre flask into which steam is passed until<br />
drops <strong>of</strong> oil cease to distil. After the liquid has cooled the water is<br />
poured <strong>of</strong>f and the residue is washed several times with water.<br />
When as much as possible <strong>of</strong> the water has been removed the material<br />
in the flask is dissolved by adding alcohol and warming on the water<br />
bath, and the solution is filtered. On leaving the filtrate over night<br />
in a cool place the base separates in colourless crystals which are<br />
collected at the pump, washed with alcohol and dried in air on several<br />
folds <strong>of</strong> filter paper. A second crop <strong>of</strong> crystals can be obtained by<br />
concentrating the mother liquor. Should the base not crystallise,<br />
but separate as an oil-—as <strong>of</strong>ten happens after the filtered solution<br />
has stood for a short time—it follows that too little alcohol has been<br />
used. In such cases somewhat more alcohol is added and the<br />
mixture is heated until the oil dissolves. Yield 20-24 g.<br />
1 Otto Fischer, Annakn, 1881, 206, 83; 1883, 217, 250.
MALACHITE GKBBN 325<br />
Oxidation <strong>of</strong> the Leuco-Base.—In a round-bottomed flask<br />
(capacity 1-5 1.) 11 g. <strong>of</strong> the dried preparation are dissolved in 80 c.c.<br />
<strong>of</strong> hot 2 iV-hydrochloric acid and the practically colourless solution is<br />
diluted with 800 c.c. <strong>of</strong> water. To the diluted solution, which is kept<br />
cool in ice and continually shaken, a suspension <strong>of</strong> 9 g. <strong>of</strong> lead dioxide<br />
in 30 c.c. <strong>of</strong> water is added slowly in small portions. Since commercial<br />
lead dioxide <strong>of</strong>ten reacts badly the oxidising agent should be<br />
prepared in the laboratory by the method given below.<br />
To the solution <strong>of</strong> the dye so obtained (and filtered if necessary)<br />
a clear concentration solution <strong>of</strong> zinc chloride (12 g.) is added, and<br />
then the zinc chloride double salt <strong>of</strong> the dye is precipitated by addition<br />
<strong>of</strong> saturated brine. (Test with a spot on filter paper to see<br />
whether the solution is nearly colourless.) To purify the dye, which<br />
has been collected at the pump and washed with brine, it is redissolved<br />
in hot water and, after cooling, salted out as above. Yield<br />
9-10 g.<br />
Lead Dioxide.—Good bleaching powder (50 g.) is vigorously<br />
shaken with water (750 c.c.); the mixture is filtered through a<br />
pleated filter and the filtrate is added gradually in small portions to<br />
a solution <strong>of</strong> lead acetate (25 g. in 100 c.c. <strong>of</strong> water) which is heated<br />
in a porcelain basin on the boiling water bath. When the originally<br />
pale precipitate has become dark brown a sample <strong>of</strong> the filtered<br />
solution is heated with more bleaching powder solution. If precipitation<br />
again occurs, more oxidising agent is added. Finally,<br />
the solution is decanted and the lead dioxide is repeatedly digested<br />
with hot water, collected at the pump, and thoroughly washed. The<br />
moist paste, dried as far as possible at the pump, is preserved in a<br />
closed glass bottle.<br />
If no fresh bleaching powder is available, a hypochlorite solution<br />
is prepared by passing chlorine into an ice-cooled solution <strong>of</strong> 15 g. <strong>of</strong><br />
sodium hydroxide in 250 c.c. <strong>of</strong> water, until the increase in weight is<br />
14 g.<br />
Assay <strong>of</strong> the Lead Dioxide Paste.—Although by drying and weighing<br />
a known amount <strong>of</strong> the moist lead dioxide its content <strong>of</strong> the pure substance<br />
can be approximately determined, the amount <strong>of</strong> active oxygen<br />
should nevertheless be ascertained with a view to greater accuracy.<br />
For this purpose 0-3-0-5 g. <strong>of</strong> the moist material (taken from the centre<br />
<strong>of</strong> the batch) is weighed out and transferred to a small conical flask<br />
(150 c.c.) into which a solution <strong>of</strong> 2 g. <strong>of</strong> potassium iodide in 5 c.c. <strong>of</strong><br />
water is poured with vigorous shaking. The mixture is now cooled in
326 FLUOKBSCBIN<br />
ice and 15 c.c. <strong>of</strong> concentrated hydrochloric acid are added. After<br />
diluting the solution thus obtained to about 50 c.c. the liberated iodine<br />
is titrated with 0-1 iV-thiosulphate solution, prepared with sufficient<br />
accuracy by dissolving 6-2 g. <strong>of</strong> pure sodium thiosulphate (Na2S2O3 +<br />
5 H2O) in water and diluting in a measuring flask to 250 c.c. 1 c.c. <strong>of</strong><br />
0-1 iV r -thiosulphate=0-012 g. <strong>of</strong> PbO2.<br />
5. FLUORESCEIN AND EOSIN 1<br />
Phthalic anhydride (15 g.) is intimately ground in a mortar with<br />
22 g. <strong>of</strong> resorcinol, and the mixture is heated in an oil bath to 180°.<br />
For this purpose an internally glazed meat-extract jar is convenient;<br />
it is suspended in the bath by means <strong>of</strong> a wire triangle fastened<br />
round the neck <strong>of</strong> the jar. 7 g. <strong>of</strong> zinc chloride, previously dehydrated<br />
by fusing and then powdered, are stirred with a glass rod into<br />
the molten mass during the course <strong>of</strong> ten minutes. The temperature<br />
is then raised to 210° and the heating is continued until the mass,<br />
which becomes progressively more viscous, has completely solidified ;<br />
for this one to two hours are required. By means <strong>of</strong> a sharp instrument,<br />
preferably a chisel, the brittle melt obtained on cooling is<br />
chipped out <strong>of</strong> the jar, powdered finely, and boiled for ten minutes in<br />
a porcelain basin with 200 c.c. <strong>of</strong> water and 10 c.c. <strong>of</strong> concentrated<br />
hydrochloric acid. In this way the unchanged starting materials and<br />
the basic zinc salt are dissolved. The fluorescein is then separated<br />
from the aqueous liquid by filtration, washed with water until the<br />
filtrate is no longer acid, and dried on the water bath. Yield,<br />
almost quantitative. Dissolve a particle <strong>of</strong> the preparation in a little<br />
ammonia and dilute in a beaker with one litre <strong>of</strong> water.<br />
Eosin.—Into a flask containing 16-5 g. (0-05 mole) <strong>of</strong> fluorescein<br />
under 80 c.c. <strong>of</strong> alcohol, 36 g. (12 c.c.) <strong>of</strong> bromine are dropped with<br />
shaking from a tap funnel during the course <strong>of</strong> twenty minutes.<br />
When half the bromine has been added, and the fluorescein has been<br />
converted into dibrom<strong>of</strong>luorescein, all the solid material disappears<br />
temporarily, since dibrom<strong>of</strong>luorescein is soluble in alcohol, but later<br />
the sparingly soluble eosin begins to crystallise.<br />
After standing for two hours the mixture is filtered and the<br />
precipitate, after being washed several times with alcohol, is dried<br />
on the water bath. The material so obtained still contains alcohol<br />
<strong>of</strong> crystallisation, which is removed by drying at 110°, when the<br />
colour becomes lighter. Observe the magnificent fluorescence<br />
1 Bacyer, Caro, Annalen, 1876, 183, 1.
TKIPHBNYLMBTHANB DYES 327<br />
obtained on greatly diluting an alkaline solution <strong>of</strong> a trace <strong>of</strong> the<br />
substance.<br />
Ammonium Salt <strong>of</strong> Eosin.—Place a very stout filter paper on a<br />
flat-bottomed crystallising basin which is one-third full <strong>of</strong> concentrated<br />
aqueous ammonia solution, spread eosin to a depth <strong>of</strong> about<br />
0-5 cm. on the paper, and cover the whole with a funnel. Very soon<br />
the light red crystals acquire a darker colour, and after about three<br />
hours they are completely converted into the ammonium salt, which<br />
forms dark red crystals having a green iridescence. When a sample<br />
<strong>of</strong> the material dissolves wholly in water the reaction is known to<br />
be complete.<br />
Sodium Salt <strong>of</strong> Eosin.—Grind 6 g. <strong>of</strong> eosin with 1 g. <strong>of</strong> anhydrous<br />
sodium carbonate, transfer the mixture to a moderate-sized, widenecked,<br />
conical flask, moisten with a little alcohol, add 5 c.c. <strong>of</strong> water,<br />
and warm on the water bath until evolution <strong>of</strong> carbon dioxide ceases.<br />
To the aqueous solution <strong>of</strong> the sodium salt thus obtained now add<br />
20 g. <strong>of</strong> alcohol, heat to boiling, and filter the hot solution. From the<br />
cooled filtrate there separate beautiful brownish-red crystals with<br />
metallic lustre, <strong>of</strong>ten only after long standing. Collect them at the<br />
pump and wash with alcohol.<br />
TRIPHENYLMETHANE DYES : THEORETICAL CONSIDERATIONS<br />
A. The Basic Series.—In general, aromatic aldehydes condense with<br />
aromatic amines in the presence <strong>of</strong> zinc chloride to form triphenylmethane<br />
derivatives (0. Fischer) ; phenols and phenyl ethers behave<br />
similarly in the presence <strong>of</strong> concentrated sulphuric acid (Baeyer). The<br />
products formed are the leuco-compounds <strong>of</strong> well-known dyes.<br />
/ y , -> H<br />
!H0 + 2 / \0H<br />
Leuco-malachite green<br />
Leuco-benzaurin<br />
When pure, these leuco-compounds dissolve in acids or alkalis to<br />
H
328 TKIPHBNYLMBTHANB DYES<br />
give colourless solutions. Leuco-malachite green is a weak base <strong>of</strong> the<br />
aniline type. The dye is formed by oxidation <strong>of</strong> the base in acid solution<br />
; as in the case <strong>of</strong> dimethyl-y-phenylenediamine (p. 319), two<br />
hydrogen atoms are removed from y-positions<br />
Cl<br />
I /—\ /CeH5<br />
C <<br />
H ^ ^ H\C6H4.N(CH3)2<br />
Cl<br />
!6H4.N(CH3)2'<br />
The formation <strong>of</strong> the acid dye benzaurin takes place in a quite<br />
analogous manner. y-Tetramethyldiaminobenzophenone (Michler's<br />
ketone), which is prepared technically from dimethylaniline and phosgene,<br />
can, like benzaldehyde, be condensed with dimethylaniline in the<br />
presence <strong>of</strong> phosphorus oxychloride. In this case, however, it is not a<br />
methane derivative, a leuco-compound, which is obtained, but, as the<br />
equation shows, the carbinol stage is at once reached. As will soon be<br />
shown, however, this stage in acid solution is equivalent to the formation<br />
<strong>of</strong> the dye.<br />
[(H3C)2N.C6H4]2C:O +<br />
—• [(CH3)2N.C6H4]2C(OH)_
TKIPHBNYLMBTHANB DYES 329<br />
C,H,.NHj H,N— < >-CH2.C6H4.NH2<br />
- 2 H HN=<<br />
/== \=CH.C6H4.NH2<br />
C.H^H, H2N- / - \<br />
H<br />
/ \ r~i./r^ TT -\TTT \<br />
H<br />
- 2H JJJJ. /<br />
—* ci s<br />
Para-leuco -aniline<br />
/=\<br />
\ Q/Q JJ NH )<br />
\=^ ,<br />
Parafuchsine<br />
The technically important " new fuchsine " synthesis from a primaryaromatic<br />
amine and formaldehyde falls, in the case <strong>of</strong> aniline, into the<br />
above reaction scheme since the formation <strong>of</strong> the intermediate product,<br />
y-diaminodiphenylmethane, is readily intelligible.<br />
The Reactions <strong>of</strong> the Dyes.—The basic triphenylmethane dyes are<br />
the neutral salts <strong>of</strong> monacid quinonoid ammonium bases. Their dyeing<br />
properties are explained on the meriquinonoid principle (WiUstatter)<br />
discussed on p. 319. In the present case this principle holds intramolecularly.<br />
From fuchsonimine<br />
(fuchsone is the corresponding O-quinone) no dye salts are derived, but<br />
from the y-amino-derivative, on the other hand, which contains the<br />
benzenoid component H2N.C6H4-—, the dye known as Doebner's violet<br />
results.<br />
The members <strong>of</strong> this class dye wool and silk directly, but cotton only<br />
when the latter is mordanted by tannin. They are fast neither to<br />
acids nor to alkalis for reasons which depend on important alterations<br />
in the compounds. If a little dilute hydrochloric acid is added to an<br />
aqueous solution <strong>of</strong> crystal violet the colour changes to green. One<br />
N(CH3)2-group takes part in the change and there is formed the salt<br />
with two equivalents <strong>of</strong> acid :<br />
C6H4.N(CH3)2.HC1
330 TKIPHBNYLMBTHANE DYES<br />
In this salt the influence on the colour <strong>of</strong> one dimethylaminophenyl<br />
radicle is suppressed in consequence <strong>of</strong> the saturation <strong>of</strong> the tervalent<br />
nitrogen ; the substance produced is <strong>of</strong> the malachite green type.<br />
When a little concentrated hydrochloric acid is added the green<br />
solution becomes yellow, because now the trichloride is formed and<br />
the influence <strong>of</strong> the second benzene ring is also suppressed, so that<br />
the (yellow) fuchsonimine type is formed. All triphenylmethane dyes<br />
dissolve in concentrated sulphuric acid with an orange-yellow colour<br />
exactly like triphenylcarbinol itself (carbonium salts, Kehrmann). By<br />
diluting the solution with water a colourless solution <strong>of</strong> the tri-acid<br />
benzenoid carbinol salt can be obtained.<br />
The colour change produced by acids can be reversed by careful<br />
addition <strong>of</strong> alkali.<br />
Carry out these and the other experiments described below.<br />
Behaviour towards Alkalis.—Add a few drops <strong>of</strong> sodium hydroxide<br />
solution to the aqueous solution <strong>of</strong> a basic triphenylmethane dye. For<br />
a short time the colour remains unchanged, but soon fades and at the<br />
same time a faintly coloured flocculent precipitate separates. In all<br />
cases this is the carbinol to which repeated reference has already been<br />
made; when pure it is colourless. In the case <strong>of</strong> crystal violet the<br />
carbinol is [(CH3)2N.C6H4]3COH.<br />
As long as the solution which has been made alkaline retains its<br />
colour the ammonium colour base, which preserves the quinonoid structure<br />
<strong>of</strong> the dye, is still present (Hantzsch). This base is stable for a<br />
short time only and can in no case be isolated. The disappearance <strong>of</strong><br />
the quinonoid system, which rapidly follows, occurs either through a<br />
rearrangement <strong>of</strong> the genuine base to the so-called pseudo- or carbinolbase,<br />
accompanied by the wandering <strong>of</strong> the OH-group :<br />
H OH<br />
or, more probably, through the addition <strong>of</strong> water to the quinonoid<br />
system to form<br />
OH [H "OH:<br />
from which the water attached to the nitrogen is subsequently again<br />
eliminated.<br />
Those dyes which, in contrast to malachite green and crystal violet,<br />
do not have the nitrogen in tertiary combination, for example, fuchsine,<br />
can lose water from their colour bases by direct elimination <strong>of</strong> its elements<br />
from their attachment to nitrogen and change into derivatives
PHTHALBINS 331<br />
<strong>of</strong> fuchsonimine. Thus there is formed from parafuchsine the orangecoloured<br />
base called after Homolka :<br />
H<br />
which changes into the carbinol by the addition <strong>of</strong> water and is reconverted<br />
into the dye by treatment with acid.<br />
When the colourless carbinol base is treated with acid the quinonoid<br />
structure is re-formed and the dye produced. But on dissolving<br />
cautiously, with cooling, it can be seen that the colour attains its maximum<br />
depth only gradually. Hence the exceedingly unstable colourless<br />
carbinol salt is first formed ; it changes into the dye with spontaneous<br />
elimination <strong>of</strong> water :<br />
H H Cl<br />
B. The Fhthaleins.—If two molecules <strong>of</strong> a phenol and one molecule<br />
<strong>of</strong> phthalic anhydride are caused to interact under the conditions which<br />
prevail during the Friedel-Crafts synthesis (Chap. IX. p. 342), the<br />
tendency <strong>of</strong> the ketone first formed to combine with a second molecule<br />
<strong>of</strong> the phenol outweighs condensation to the anthraquinone derivative ;<br />
in this way are formed the fhthaleins, discovered by Baeyer in 1871.<br />
This process may be discussed by taking phenolphthalein as an example.<br />
__>. • • — > 0H -<br />
The intermediate product undergoes an aldol condensation with a<br />
second molecule <strong>of</strong> phenol, <strong>of</strong> which the y-position is involved along<br />
with the C=O group in exactly the same way as Michler's ketone condenses<br />
with dimethylaniline, as described above.<br />
>OH<br />
HJOOH<br />
The y-dihydroxytriphenylcarbinol o-carboxylic acid, which cannot
332 FLUOKBSCBIN<br />
be isolated, loses water between the COOH- and OH-groups, which are<br />
favourably situated with respect to each other; the acid is thus converted<br />
into the lactone, phenolphthalein :<br />
C=(C6H4OH)2<br />
The colourless lactone is hydrolysed by alkalis and the intensely<br />
red alkali salts, well known in volumetric analysis, are formed. In<br />
them one benzene ring has assumed the quinonoid form with elimination<br />
<strong>of</strong> water in the manner expressed in the following equation :<br />
JOOH<br />
OH<br />
The red salts are the di-alkali salts <strong>of</strong> the quinonoid phenolcarboxylic<br />
acid formulated. This acid is not stable in the free state, but undergoes<br />
immediate isomerisation to the colourless lactone.<br />
Phenolphthalein is a triphenylmethane derivative and can easily<br />
be connected with fuchsone, the parent substance <strong>of</strong> the dyes which<br />
belong to this series. Fuchsone is diphenylquinomethane and is<br />
obtained from y-hydroxytriphenylcarbinol by elimination <strong>of</strong> water<br />
(Bistrzycki) :<br />
OH<br />
C 6 H 5\J.<br />
C6H/<br />
In complete accordance with Willstatter's theory, fuchsone is only<br />
yellowish-orange in colour. But if, in addition, one <strong>of</strong> the two free<br />
benzene rings has an OH-group in the y-position, we have the dye<br />
benzaurin already mentioned on p. 328. The o-carboxylic acid <strong>of</strong> this<br />
dye is the quinonoid form <strong>of</strong> phenolphthalein. In fact, the colour tones<br />
<strong>of</strong> these two substances are very similar. Phenolphthalein is decolorised<br />
by concentrated alkali; NaOH (KOH) is added on and the<br />
trisodium (or potassium) salt <strong>of</strong> the benzenoid carbinol form is produced.<br />
(Try these reactions with phenolphthalein.)<br />
Fluorescein.—In this case the reaction undergoes an extension.<br />
The two OH-groups <strong>of</strong> the resorcinol molecule which are oriho to the<br />
position <strong>of</strong> condensation together form an oxygen bridge and hence<br />
a new ring (the xanthane ring) results by elimination <strong>of</strong> water :
COOH<br />
Since fluorescein is coloured it seems that the quinonoid formula<br />
on the right is the probable one even for the free compound, and that<br />
the lactone formula is doubtful.<br />
In eosin the four bromine atoms are grouped in pairs, in the opositions<br />
indicated by asterisks in the formula. Eosin, also, must be<br />
regarded as quinonoid, especially because its reduction product, leucoeosin,<br />
is colourless.<br />
Experiment;—Dissolve some eosin in sodium hydroxide solution<br />
and boil with zinc dust until the mixture is colourless. Decant the<br />
solution. Acidify one portion <strong>of</strong> the decanted liquid and leave the<br />
other portion to stand in an open dish.<br />
Like quinone itself, its derivatives are also converted by reducing<br />
agents into colourless benzenoid hydrogenated products (in the case <strong>of</strong><br />
the dyes they are called " leuco-compounds "). The following scheme<br />
expresses this process for eosin as well as for the other dye :<br />
-OH.<br />
Many leuco-compounds are reconverted into the dye even by the<br />
oxygen <strong>of</strong> the atmosphere ; leuco-indigo (p. 373) and leuco-eosin are<br />
examples <strong>of</strong> this.<br />
The most magnificent dyes, which are chiefly used in the dyeing <strong>of</strong><br />
silk, are relatives <strong>of</strong> eosin obtained from di- and tetra-chlorophthalic<br />
anhydride (phloxine, rose bengale). The (basic) rhodamines also belong<br />
to this class. They are produced by condensation <strong>of</strong> phthalic anhydride<br />
with m-aminophenols (in place <strong>of</strong> resorcinol); the dye containing<br />
the diethylated NH2-group, in particular, is <strong>of</strong> great technical<br />
importance.<br />
Finally gallein may be mentioned ; in it pyrogallol is the phenolic<br />
component.<br />
The conversion <strong>of</strong> the phthaleins into anthracene derivatives, the<br />
so-called phihalideins, need not be detailed here.
334 ALIZAKIN<br />
6. ALIZARIN<br />
A mixture <strong>of</strong> 2 g. <strong>of</strong> potassium chlorate, 30 g. <strong>of</strong> commercial<br />
sodium hydroxide, 10 g. <strong>of</strong> finely powdered sodium j8-anthraquinonesulphonate<br />
(" silver salt "), and 40 c.c. <strong>of</strong> water is heated for twenty<br />
hours at 170° (oil bath) in an autoclave or in an iron tube with<br />
sere wed-on cap. The cooled melt is repeatedly extracted with hot<br />
water and the extracts, after being combined and filtered, are<br />
acidified while hot with excess <strong>of</strong> hydrochloric acid, which precipitates<br />
the alizarin. When the mixture has cooled the precipitate<br />
is collected at the pump, washed successively with dilute hydrochloric<br />
acid and water, and dried.<br />
For purification the crude product is boiled with glacial acetic<br />
acid (preferably in the extraction apparatus shown in Fig. 27). Fine<br />
red needles ; melting point 289°. Sublimation in a vacuum from<br />
a sausage flask is also to be recommended ; the " sausage " should<br />
be fixed low down and the bulb completely immersed in a nitrate<br />
bath (equal parts <strong>of</strong> potassium and sodium nitrates). Much poorer<br />
yields <strong>of</strong> alizarin are obtained by using an open round-bottomed<br />
flask at 189°-190°.<br />
Alizarin or l:2-dihydroxyanthraquinone is one <strong>of</strong> the most important<br />
dyes. Like indigo, the dye occurs in the plant (the madder<br />
root) as the glucoside <strong>of</strong> the leuco-compound. The cultivation <strong>of</strong> the<br />
madder plant, which, chiefly in southern France, extended over large<br />
areas, was brought to an end by the synthesis <strong>of</strong> the dye from the<br />
anthracene <strong>of</strong> coal-tar (Graebe and Liebermann, 1869). By distillation<br />
with zinc dust according to the method <strong>of</strong> Baeyer, these two<br />
chemists had previously obtained anthracene from alizarin.<br />
Anthracene can be oxidised directly to its meso-quinone, anthraquinone,<br />
by means <strong>of</strong> chromic acid. For almost all its reactions the<br />
middle ring <strong>of</strong> anthracene provides the point <strong>of</strong> attack.<br />
Experiment.—Dissolve 1 g. <strong>of</strong> purest anthracene in just sufficient<br />
good glacial acetic acid at the boiling point; without further heating<br />
add 3 c.c. <strong>of</strong> concentrated sulphuric acid and, drop by drop, 4 g. <strong>of</strong><br />
sodium dichromate dissolved in a quite small amount <strong>of</strong> water.<br />
(Neglect any turbidity or precipitate which appears after the addition<br />
<strong>of</strong> the sulphuric acid.) A very vigorous reaction occurs and the<br />
chromic acid is used up almost immediately ; after all the dichromate<br />
has been added boil for five minutes longer. Dilute the solution.<br />
The anthraquinone separates in a flocculent condition. After
QUINIZAKIN 335<br />
collecting the substance at the pump, wash with water and dry.<br />
Recrystallise from glacial acetic acid. Fine pale yellow needles ;<br />
melting point 285°.<br />
When completely pure the compound is colourless. Compare with<br />
benzoquinone and naphthoquinone.<br />
Anthraquinone is reduced by heating with sodium hydroxide and<br />
zinc dust: the deep red disodium salt <strong>of</strong> anthraquinol goes into solution.<br />
Carry out the reduction and filter the red solution. Anthraquinone<br />
soon separates again from the nitrate on exposure to the air.<br />
Details <strong>of</strong> the interesting desmotropic phenomena exhibited by the<br />
hydroxyanthracenes are given by K. H. Meyer (Annalen, 1911, 379, 37).<br />
Meso-hydroxy- and dihydroxyanthracene exist in two forms, a genuine,<br />
coloured acidic enol which fluoresces in solution and a colourless,<br />
neutral keto-iovm.<br />
OH<br />
\<br />
H H<br />
H OH<br />
Anthranol •—•->-<br />
Anthrone Anthraquinol -
336 NAPHTHAZAKIN<br />
namely, by reductive-oxidative fusion with fuming sulphuric acid and<br />
sulphur (S2O3) in the presence <strong>of</strong> boric acid (R. Bohn, R. E. Schmidt).<br />
The production <strong>of</strong> naphthazarin from 1 : 5- or 1 : 8-dinitronaphthalene<br />
under similar conditions constitutes a more readily intelligible prototype<br />
<strong>of</strong> this complicated reaction.<br />
It consists essentially in a rearrangement to the quinoneoxime, which<br />
is then hydrolysed and partially reduced.<br />
0 NOH<br />
NOHO
CHAPTBK IX<br />
THE GEIGNAED AND FEIEDEL-CEAFT8 SYNTHESES.<br />
OEGANIC EADICLES<br />
THE GRIGNARD REACTION<br />
1. PREPARATION OF ALCOHOLS<br />
(a) BENZOHYDROL FROM BENZALDEHYDE AND PHENYL<br />
MAGNESIUM BROMIDE<br />
A SMALL, dry, round-bottomed flask is fitted with a branched neck<br />
attachment and the oblique branch is connected with a reflux condenser<br />
closed at the upper end with a calcium chloride tube.<br />
Through the stopper <strong>of</strong> the upright branch a dropping funnel with a<br />
long outlet tube is inserted. The flask contains 3-2 g. <strong>of</strong> magnesium<br />
shavings, on to which a mixture <strong>of</strong> 20 g. <strong>of</strong> pure, constant-boiling<br />
bromobenzene and 50 c.c. <strong>of</strong> absolute ether is dropped gradually<br />
from the funnel. After about a quarter <strong>of</strong> the mixture has been<br />
added the operation is interrupted until evolution <strong>of</strong> heat and ebullition<br />
<strong>of</strong> the ether indicate the beginning <strong>of</strong> the reaction. Occasionally<br />
there is an obstinate delay ; by holding a basin with warm<br />
water under the flask, or, better by dropping in a particle <strong>of</strong> iodine,<br />
the reaction can be started with rapidity and certainty. When<br />
preparing the phenyl magnesium bromide solution it is important<br />
to keep the process in check by cooling from time to time and by<br />
regulating the inflow <strong>of</strong> bromobenzene so that the reaction just<br />
continues <strong>of</strong> its own accord. The bromobenzene which adheres to<br />
the dropping funnel is washed into the flask with a little absolute<br />
ether. When most <strong>of</strong> the metal has dissolved and the reaction<br />
becomes noticeably slacker, the solution is boiled for some time<br />
by dipping the flask into a basin <strong>of</strong> warm water until only a few<br />
particles <strong>of</strong> magnesium remain in suspension.<br />
The solution is now cooled in ice-water and 10-6 g. <strong>of</strong> freshly<br />
337 z
338 BENZOHYDKOL AND TKIPHENYLCAKBINOL<br />
distilled benzaldehyde mixed with 10 c.c. <strong>of</strong> ether are rapidly added<br />
drop by drop, at first with continued cooling.<br />
To complete the reaction the solution is boiled for fifteen minutes<br />
under reflux and again cooled. External cooling is continued,<br />
20-30 g. <strong>of</strong> ice are then added in one portion, followed by sufficient<br />
hydrochloric acid to dissolve the magnesium hydroxide which is<br />
precipitated (about 10 c.c. <strong>of</strong> concentrated acid plus 10 c.c. <strong>of</strong> water).<br />
The ether layer is now separated in a funnel and the aqueous layer<br />
is extracted with a little fresh ether. If a glass rod after dipping into<br />
the ethereal solution still smells <strong>of</strong> benzaldehyde, half <strong>of</strong> the ether is<br />
evaporated and the remaining solution is vigorously shaken for five<br />
minutes with a few cubic centimetres <strong>of</strong> 40 per cent bisulphite solution,<br />
then with a little sodium carbonate solution to remove dissolved<br />
sulphur dioxide ; the ethereal solution is next dried for a short time<br />
with calcium chloride. On evaporating the ether the benzohydrol<br />
remains as an oil which soon solidifies. Yield, after pressing on<br />
porous plate, 12-14 g. The alcohol can be recrystallised from ligroinor<br />
from a little spirit. Beautiful colourless prisms; melting point 68°.<br />
If the formation <strong>of</strong> the Grignard compound proceeds too violently<br />
the reaction product usually contains considerable amounts <strong>of</strong> diphenyl<br />
because <strong>of</strong> the reaction :<br />
C6H5MgBr + BrC6H5 — •> C6HS.C6HS + MgBr2 .<br />
(6) TRIPHENYLCARBINOL FROM ETHYL BENZOATE AND<br />
PHENYL MAGNESIUM BROMIDE<br />
Ethyl benzoate (15 g.) mixed with 15 c.c. <strong>of</strong> absolute ether is<br />
dropped into a Grignard solution prepared as just described from<br />
6-4 g. <strong>of</strong> magnesium and 40 g. <strong>of</strong> bromobenzene. The conditions<br />
are the same as those observed in the preceding preparation;<br />
at the end the solution is boiled for half an hour and worked up as<br />
before. Colourless prisms <strong>of</strong> triphenylcarbinol, melting point 162°,<br />
are obtained by recrystallising the solid residue from hot alcohol.<br />
Yield over 20 g. For further information about this important<br />
alcohol see p. 355.<br />
2. SYNTHESIS OF A KETONE FROM A NITRILE.<br />
ACETOPHENONE 1<br />
An ethereal solution <strong>of</strong> phenyl magnesium bromide is prepared<br />
1 Blaise, Compt. rend., 1901, 133, 1217.
ACETOPHBNONB FKOM BKOMOBBNZBNE 339<br />
from 6-4 g. <strong>of</strong> magnesium and 40 g. <strong>of</strong> bromobenzene according to<br />
the procedure given under 1 (a), and to this solution 8 g. <strong>of</strong> acetonitrile<br />
diluted with an equal volume <strong>of</strong> ether are added drop by drop.<br />
The mixture is then kept boiling on the water bath for one hour more,<br />
poured on to ice in a round-bottomed flask (capacity 1 1.), mixed<br />
with 100 c.c. <strong>of</strong> approximately 8 i^-sulphuric acid, and submitted<br />
to distillation with steam. The ether and the acetophenone<br />
produced pass over with the steam. The distillate is extracted<br />
with ether, the extract is dried with calcium chloride, the ether is<br />
evaporated, and the ketone which remains is distilled. Boiling point<br />
202°. Yield 10-12 g. = 45-50 per cent <strong>of</strong> the theoretical.<br />
Here also a purer product is obtained by distillation in vacuo<br />
Boiling point 88°/12 mm. In any case the acetophenone must be<br />
water-white and must crystallise when cooled with ice. Melting<br />
point 22°.<br />
As a change phenylacetone may be prepared from benzyl magnesium<br />
chloride and acetonitrile. This ketone is purified by way <strong>of</strong><br />
the bisulphite compound and distilled in a vacuum. The yield,<br />
with respect to acetonitrile, does not exceed 25 per cent.<br />
Explanations relating to 1 and 2<br />
Grignard Reagents.—Magnesium metal dissolves in alkyl halides<br />
in the presence <strong>of</strong> absolute ether to form organo-metallic compounds<br />
<strong>of</strong> the type R—Mg—Hal. Arylhalides act in the same way. In both<br />
series the iodides react most rapidly, then come the bromides, and lastly<br />
the chlorides. Often the reaction exhibits a somewhat stubborn unwillingness<br />
to begin : by addition <strong>of</strong> a little iodine or else <strong>of</strong> ethyl<br />
iodide this difficulty can be overcome. Occasionally it is necessary to<br />
activate the magnesium by heating with iodine (von Baeyer). The<br />
ether required for the reaction is bound, to the extent <strong>of</strong> two molecules,<br />
as a complex addition compound (Meisenheimer); it can be replaced<br />
by tertiary amines. In solution the organo-magnesium halides are<br />
partly decomposed to form an equilibrium mixture thus (W. Schlenk,<br />
jun.) :<br />
2R.Mg.Hal ^=± Mg.R2 + Mg.Hal2.<br />
Grignard reagents are, quite generally, decomposed according to<br />
the following equation by substances which contain reactive hydrogen :<br />
R.Mg.Hal + HRj > RH + Rj.Mg.Hal.<br />
In all cases, therefore, the hydrocarbon RH, corresponding to the<br />
halide used, is formed.
340 THE GKIGNAKD KBACTION<br />
The simplest example <strong>of</strong> this type is decomposition by water :<br />
HgC.Mg.I + HOH >• CH4 + HO.Mg.I.<br />
Hence: in all experiments with Grignard reagents moisture must be<br />
completely excluded. Alcohols, phenols, carboxylic acids, primary and<br />
secondary amines, oximes, acetylene, etc., react in the same way as<br />
water.<br />
Since one reactive hydrogen atom always liberates one molecule <strong>of</strong><br />
hydrocarbon, the use <strong>of</strong> methyl magnesium iodide provides a serviceable<br />
method for determining quantitatively the proportion <strong>of</strong> active<br />
hydrogen by measuring the volume <strong>of</strong> methane liberated by a weighed<br />
amount <strong>of</strong> a substance under investigation (Zerevitin<strong>of</strong>l). The process<br />
is <strong>of</strong> considerable value for the determination <strong>of</strong> constitution. On the<br />
method <strong>of</strong> carrying it out see p. 84.<br />
In virtue <strong>of</strong> their great capacity for forming addition compounds<br />
the Grignard reagents are primarily used for synthetic purposes. What<br />
was formerly attained with the rather unmanageable zinc alkyls is<br />
nowadays accomplished in a much wider domain by means <strong>of</strong> the<br />
easily made Grignard reagents (K. Ziegler has recently also used organic<br />
lithium compounds).<br />
Quite generally addition to unsaturated systems takes place, e.g. to<br />
>C=O, >C=N—, —C=N, — N=O, but >C=C< and—CsC—do<br />
not react. The mechanism <strong>of</strong> the addition is as follows : the Grignard<br />
reagent is added on in the form <strong>of</strong> its two components R and MgHal;<br />
in the case <strong>of</strong> the C=O-double bonds the Mg-containing constituent<br />
always unites with the oxygen, R always with the carbon.<br />
If the action <strong>of</strong> methyl magnesium bromide on acetaldehyde be<br />
taken as example, the following equation holds :<br />
pTT<br />
CH3.CO + CH3.Mg.Br > CH3.c/<br />
H H M)—MgBr<br />
The addition product is decomposed by water, thus :<br />
/ 3 / 3<br />
CH3.C< +H2O > CH3.C< +HO.Mg.Br.<br />
H M)—MgBr H M)H<br />
As a result, therefore, acetaldehyde is converted into isopropyl<br />
alcohol. Quite generally it may be said that the Grignard reaction consists<br />
in the addition to the unsaturated linkage—as H and R—<strong>of</strong> the<br />
hydrocarbon corresponding to the halide used. In effect a " synthesising<br />
hydrogenation " occurs.<br />
The course <strong>of</strong> the following Grignard syntheses can thus be understood<br />
without further comment:
THE GRIGNARD KBACTION 341<br />
Formaldehyde -> primary alcohols<br />
Other aldehydes -> secondary alcohols<br />
Ketones -> tertiary alcohols<br />
Carbon dioxide -> carboxylic acids<br />
Nitriles -> ketones (via the ketimine ^C=NH).<br />
R/<br />
The reactions with the esters, chlorides, and anhydrides are somewhat<br />
more complicated.<br />
Here also, at first, the usual addition to the C=O-group takes place :<br />
OR OR<br />
| | .O-MgBr<br />
R__CO + CH3.Mg.Br —> R—C< \CH3<br />
The product so formed reacts with a second molecule <strong>of</strong> the Grignard<br />
compound according to the following equation :<br />
OR CH3<br />
I /O—MgBr I<br />
R—C< + CH3—Mg.Br—> R—C.O.MgBr + RO.MgBr.<br />
\CH3<br />
I<br />
CH3<br />
Finally, decomposition with water yields the tertiary alcohol. In<br />
the case <strong>of</strong> the esters <strong>of</strong> formic acid, used in excess, the reaction can be<br />
checked at the first stage, and by decomposing the product<br />
/Ri<br />
HC^-0—Mg—Br with water, aldehydes can be obtained.<br />
M)R<br />
The Grignard reagents also attack nitrogenous complexes in a similar<br />
way, as the example <strong>of</strong> the azides on p. 290 has shown.<br />
Nitrosobenzene can be converted into diphenylhydroxylamine<br />
(CgHgJjNOH (p. 182) by the action <strong>of</strong> phenyl magnesium bromide.<br />
The wide range over which the Grignard synthesis can be applied<br />
should be sufficiently evident from this short review.<br />
There remains to be mentioned a secondary reaction which <strong>of</strong>ten<br />
takes place, undesired, in the preparation <strong>of</strong> Grignard reagents, but is<br />
also sometimes aimed at.<br />
The Grignard compounds react with varying ease with organic<br />
halides in the manner <strong>of</strong> the Wurtz reaction according to the equation :<br />
R.Mg.Hal + RjHal >• R.Rj + MgHal2 .<br />
Hence diphenyl, as was already mentioned, is always obtained as a<br />
by-product in the preparation <strong>of</strong> phenyl magnesium bromide.<br />
The organo-magnesium compounds are sensitive to the action <strong>of</strong><br />
oxygen. This must always be kept in mind if they are not used
342 ALUMINIUM CHLOKIDB<br />
immediately after they are prepared (cf. also Zerevitin<strong>of</strong>Fs determination<br />
on p. 84).<br />
The great variety <strong>of</strong> synthetic processes included in the Grignard<br />
reaction may be illustrated by the production <strong>of</strong> diphenlymethyl<br />
carbinol and consequently <strong>of</strong> unsymmetrical diphenylethylene :<br />
1. From benzophenone and methyl magnesium bromide :<br />
/OH<br />
(C6H5)2.CO + CH3.Mg.Br —•> (C6H5)2:C< .<br />
2. From ethyl acetate and phenyl magnesium bromide :<br />
CH3.COOC2H5 + 2C6H5.Mg.Br —><br />
H<br />
Related to the Grignard synthesis is that <strong>of</strong> Reformatzky in which<br />
zinc is used to condense the esters <strong>of</strong> a-halogenated fatty acids with<br />
ketones, e.g. :<br />
(CH3)2:C=CH.CH2.CH2.CO.CH3 + Zn + C1H2C.CO2R<br />
Methvlheptenone<br />
OH<br />
> (CH3)2:C=CH.CH2.CH2.C.CH2.CO2R<br />
H3<br />
CH3<br />
- H '° (CH3)2C:CH.CH2.CH2.C(CH3):CH.CO2H<br />
hydrolysis Geranic acid<br />
THE FRIEDEL-GRAFTS SYNTHESIS<br />
Aluminium Chloride.—For the success <strong>of</strong> a Friedel-Crafts synthesis<br />
it is essential that the quality <strong>of</strong> the aluminium chloride used<br />
as catalyst should be beyond reproach. Commercial preparations<br />
are <strong>of</strong>ten partially decomposed and unfit for use in consequence <strong>of</strong><br />
the entrance <strong>of</strong> moisture into insufficiently closed containers. In<br />
order to make sure, a small sample should be heated over a flame in a<br />
test tube held obliquely ; the whole, or at least the bulk, <strong>of</strong> the<br />
chloride should sublime. Preparations which are not too seriously<br />
decomposed can be made fit for use by resublimation.<br />
If it is necessary to prepare the aluminium chloride in the laboratory<br />
the following method should be used. 1<br />
Connect a wide (3-5-4 cm.) hard glass tube, e.g. a tube used for<br />
combustions by Dennstedt's method, by means <strong>of</strong> a cork with a wide-<br />
1 It is recommended that aluminium chloride obtained during preparative work<br />
in the inorganic department <strong>of</strong> the laboratory should be employed for syntheses <strong>of</strong><br />
the type here described.
BBNZOPHBNONB 343<br />
necked bottle in such a way that the end <strong>of</strong> the tube is practically<br />
flush with the cork. Through a second hole in the cork push a<br />
narrower, yet not too narrow, bent glass tube <strong>of</strong> which the shorter<br />
arm extends rather more than half-way into the bottle. The end <strong>of</strong><br />
the longer arm extends upwards at a right angle. Along the combustion<br />
tube, to a depth equal to one-third <strong>of</strong> its diameter, arrange a'<br />
layer <strong>of</strong> aluminium filings. The length <strong>of</strong> this layer will depend on<br />
the amount <strong>of</strong> aluminium chloride (27 g. <strong>of</strong> aluminium give-—theoretically—133<br />
g. <strong>of</strong> aluminium chloride) required and on the length<br />
<strong>of</strong> the combustion furnace used, but in any case the end <strong>of</strong> the heated<br />
layer must not be more than 8 cm. from the receiving bottle. Protect<br />
the cork from the heat by means <strong>of</strong> a sheet <strong>of</strong> asbestos cut to<br />
admit the tube and fixed slightly in front <strong>of</strong> the cork.<br />
At the other end connect the tube by means <strong>of</strong> the shortest<br />
possible rubber tubes with two wash-bottles containing concentrated<br />
sulphuric acid, which in turn are connected to an efficient supply<br />
<strong>of</strong> hydrogen chloride. The whole apparatus must, <strong>of</strong> course, be<br />
perfectly dry.<br />
Lay the tube in a combustion furnace in a fume chamber and<br />
pass a current <strong>of</strong> hydrogen chloride through until the air is expelled,<br />
then slowly heat the whole length <strong>of</strong> tube containing the aluminium.<br />
When, as the temperature rises and the passage <strong>of</strong> fumes into the<br />
receiver shows that aluminium chloride is forming, increase the<br />
stream <strong>of</strong> hydrogen chloride ; at the same time also heat more<br />
strongly, and take care that at this stage an extremely vigorous<br />
current <strong>of</strong> hydrogen chloride ensures that there is no time for the<br />
aluminium chloride to condense inside the cork and so to choke the<br />
apparatus ; choking must be carefully avoided. No serious reduction<br />
in the yield is caused by the escape <strong>of</strong> clouds <strong>of</strong> aluminium<br />
chloride from the exit tube <strong>of</strong> the bottle. Continue the experiment<br />
until all but a small residue <strong>of</strong> the metal has volatilised.<br />
Keep the chloride obtained in this way in a bottle provided with<br />
a tightly fitting ground glass stopper.<br />
3. SYNTHESIS OF A KETONE<br />
(a) BENZOPHENONE FROM BENZOYL CHLORIDE AND BENZENE<br />
Freshly prepared, finely powdered aluminium chloride (35 g.),<br />
weighed in a dry corked test tube, is poured with frequent shaking<br />
during the course <strong>of</strong> ten minutes into a dry flask containing 50 c.c. <strong>of</strong>
344 BBNZOPHBNONB<br />
benzene, 35 g. (0-25 mole) <strong>of</strong> benzoyl chloride, and 100 c.c. <strong>of</strong> pure<br />
carbon bisulphide (or 70 c.c. more benzene). The flask is then<br />
attached to a long reflux condenser and warmed on the water bath<br />
at 50° until only small amounts <strong>of</strong> hydrogen chloride are being<br />
evolved (2-3 hours). The solution acquires a deep brown colour.<br />
The carbon bisulphide (or benzene) is now removed by distillation<br />
through a downward condenser and the residue is cautiously poured,<br />
while still warm, into a capacious flask containing 300 c.c. <strong>of</strong> water<br />
and small pieces <strong>of</strong> ice. After rinsing out the reaction flask with a<br />
little water and adding 10 c.c. <strong>of</strong> concentrated hydrochloric acid to<br />
the reaction mixture, steam is passed through for about twenty<br />
minutes. The material which remains in the flask is then cooled,<br />
taken up in ether and shaken several times with dilute sodium<br />
hydroxide solution. After the ethereal solution has been dried<br />
with calcium chloride and the ether has been evaporated, the residue<br />
is distilled from a flask with low side tube. Boiling point 297°.<br />
Melting point 48°. Yield about 35 g. A purer product is obtained<br />
by vacuum distillation in a sausage flask.<br />
Benzophenone Oxime<br />
To a solution <strong>of</strong> 4 g. <strong>of</strong> benzophenone in 25 c.c. <strong>of</strong> alcohol, cooled<br />
solutions <strong>of</strong> 3 g. <strong>of</strong> hydroxylamine hydrochloride in 6 c.c. <strong>of</strong> water<br />
and 5 g. <strong>of</strong> potassium hydroxide in 5 c.c. <strong>of</strong> water are added and the<br />
whole is heated under reflux on the water bath for two hours. The<br />
product is then poured into 50 c.c. <strong>of</strong> water, any unchanged ketone is<br />
removed by nitration after shaking to cause aggregation, the filtrate<br />
is faintly acidified with dilute sulphuric acid, and the free oxime<br />
recrystallised from alcohol. Melting point 140°.<br />
Beckmann Rearrangement to Benzanilide<br />
A weighed quantity <strong>of</strong> the oxime is dissolved in some cold ether,<br />
free from water and alcohol, and to the solution 1 -5 parts <strong>of</strong> finely<br />
powdered phosphorus pentachloride are gradually added. The<br />
ether is then removed by distillation and water is added to the<br />
residue with cooling : the ensuing precipitate is recrystallised from<br />
alcohol. Melting point 163°.<br />
The interesting intramolecular rearrangement 1 which is brought<br />
1 E. Beckmann, Ber., 1886, 19, 988; 1887, 20, 1507, 2580; Annalen, 1889,<br />
252, 1, 44.
THE BBCKMANN KEAKKANGBMBNT 345<br />
about in this way involves an exchange <strong>of</strong> the positions <strong>of</strong> C6H5 and<br />
OH according to the scheme :<br />
>C:NOH > C6HB.C:N.C6H6 > C6H5.CO.NH.C6H5 .<br />
C6H/A I I<br />
1 1 OH<br />
Under the influence <strong>of</strong> the catalyst (PC15, concentrated H28O4) a<br />
compound rich in energy is converted into its stable isomeride ; the<br />
change which occurs is similar to that which was discussed on pp. 186,<br />
187 in connexion with the relationship between hydrazobenzene and<br />
benzidine. A comparison with the benzilic acid rearrangement also<br />
suggests itself.<br />
KOCO.C:(C6HS)2,<br />
OH<br />
There is also some relationship to the degradation reactions <strong>of</strong><br />
H<strong>of</strong>mann and Curtius.<br />
In this connexion the spatial isomerism <strong>of</strong> the oximes must also be<br />
mentioned. A theory for this type <strong>of</strong> isomerism had already been<br />
suggested by Werner and Hantzsch and is similar to that already discussed<br />
in the case <strong>of</strong> the diazotates. According to this theory, those<br />
oximes in which the C-atom bearing the isonitroso-group is also united<br />
to two different radicles exist in a syn- and an anti-ioim.:<br />
R__C—E' E—C—E'<br />
I and ||<br />
HON NOH<br />
In a model the isomerism is seen to be <strong>of</strong> the same kind as that <strong>of</strong><br />
maleic and fumaric acids.<br />
The syn-ioim <strong>of</strong> aldoximes is readily dehydrated to the nitrile, the<br />
anti-ioim is not.<br />
E.CH E.C<br />
NOH N<br />
For a long time it was supposed that the results <strong>of</strong> the Beckmann<br />
rearrangement <strong>of</strong> ketoximes afforded pro<strong>of</strong> <strong>of</strong> their configuration; the<br />
OH-group was thought to change places with the adjacent substituent,<br />
for the rearrangement <strong>of</strong> the two stereoisomeric ketoximes leads to<br />
isomeric amides. Eecently it has been shown, however, that just the<br />
opposite is the case, as the following formulae indicate (Meisenheimer,<br />
Ber., 1921, 54, 3206) :
346 ISOMBKIC OXIMBS. ACBTOPHBNONB<br />
E.C.E' OC.K' R.C.R' OCR<br />
II —• I ; II —• I •<br />
NOH NH.R HON NHR'<br />
In excellent agreement with the theory, benzil yields two stereoisomeric<br />
monoximes and three dioximes :<br />
H5C6.C C.C6HS H5C6.C-C.C6H5 H5C6.C C.C6H5<br />
II II II II II II<br />
NOH HON HON NOH HON HON<br />
syn- anti- amphi-foiva<br />
(b) ACETOPHENONE FROM BENZENE AND ACETIC ANHYDRIDE !<br />
A stirrer with mercury seal (Fig. 30, p. 39) is fitted into the<br />
middle neck <strong>of</strong> a three-necked round-bottomed flask (so-called<br />
Tscherniak flask ; capacity 500 c.c.) or wide-necked round-bottomed<br />
flask and the other two necks are provided respectively with a reflux<br />
condenser and a dropping funnel. The flask contains 100 c.c. <strong>of</strong><br />
sodium-dried benzene and 80 g. <strong>of</strong> freshly sublimed aluminium<br />
chloride. Pure acetic anhydride, 25 g., is then run in with vigorous<br />
stirring during the course <strong>of</strong> half an hour. The mixture becomes<br />
warm and a very brisk evolution <strong>of</strong> hydrogen chloride takes place.<br />
After heating to boiling on the water bath with continuous stirring<br />
for half an hour more, the cooled solution is poured on to ice in a<br />
separating funnel and the aluminium hydroxide precipitated is<br />
dissolved by concentrated hydrochloric acid. Some ether is added,<br />
the benzene layer is separated, the aqueous layer is extracted with<br />
ether, and the combined benzene and ether solutions are shaken<br />
with sodium hydroxide solution. When the solution has been dried<br />
with calcium chloride and the solvents have evaporated the acetophenone<br />
is distilled, preferably in a vacuum. See p. 339. Yield<br />
24-25 g.; calculated on the acetic anhydride, 80-85 per cent <strong>of</strong> the<br />
theoretical.<br />
When acetyl chloride is used instead <strong>of</strong> acetic anhydride hardly<br />
half this yield is obtained. Comparison <strong>of</strong> the two reactions is<br />
instructive.<br />
4. TRIPHENYLCHLOROMETHANE FROM BENZENE AND<br />
CARBON TETRACHLORIDE 2<br />
In the apparatus used for the preparation <strong>of</strong> benzophenone 60 g.<br />
<strong>of</strong> fresh active aluminium chloride are gradually added to a mixture<br />
1 B. Adams, J. Amer. Chem. Soc., 1924, 46, 1889.<br />
2 M. Gomberg, Ber., 1900, 33, 3144.
TKIPHBNYLCHLOKOMBTHANB 347<br />
<strong>of</strong> 80 g. <strong>of</strong> pure dry carbon tetrachloride and 200 g. <strong>of</strong> benzene. At<br />
first the flask is kept cool with water and the reaction is not allowed<br />
to become too violent. The copious fumes <strong>of</strong> hydrogen chloride are<br />
absorbed as described in similar cases, e.g. in the preparation <strong>of</strong><br />
bromobenzene (p. 103). When all the aluminium chloride has been<br />
added and the main reaction is over, the mixture is heated under<br />
reflux on the boiling water bath for half an hour longer and the<br />
brownish-yellow reaction mixture, after cooling, is poured, with<br />
constant shaking, into a sufficiently large separating funnel containing<br />
a mixture <strong>of</strong> 100-200 g. <strong>of</strong> ice with 200 c.c. <strong>of</strong> concentrated<br />
hydrochloric acid. If the ice melts before the whole <strong>of</strong> the mixture<br />
has decomposed, more ice and an equal amount <strong>of</strong> concentrated<br />
hydrochloric acid are added. The purpose <strong>of</strong> the hydrochloric acid<br />
is to prevent the hydrolysis <strong>of</strong> the triphenylmethyl chloride. When<br />
the two layers <strong>of</strong> liquid in the funnel have separated—perhaps after<br />
the addition <strong>of</strong> fresh benzene—the aqueous portion is removed, and<br />
extracted again, if necessary, with benzene. The combined benzene<br />
solutions are dried with calcium chloride and then as much benzene as<br />
•possible is evaporated on the water bath. The residue is digested<br />
with an equal volume <strong>of</strong> ether and cooled for some hours in ice.<br />
Then the crystalline sludge is filtered at the pump on a wide filter<br />
plate and the solid, after being pressed down well, is washed several<br />
times with a little ice-cold ether. A second, less pure, crop <strong>of</strong><br />
crystals is obtained by concentrating the mother liquor (ultimately<br />
in vacuo), digesting the residue with a little cold ether, and filtering<br />
at the pump. Yield 110-120 g.<br />
For purification the still yellow crude product is dissolved in very<br />
little warm benzene, four volumes <strong>of</strong> light petrol are added, and<br />
crystallisation is induced by cooling in ice and stirring with a glass<br />
rod. The crystals are washed with cold petrol ether.<br />
Distillation in a high vacuum also yields a very pure preparation<br />
(Lecher).<br />
5. 2 : 4-DIHYDR0XYACET0PHEN0NE FROM RESORCINOL AND<br />
ACETONITRILE x<br />
Finely powdered anhydrous zinc chloride (2 g.) is added to a<br />
solution <strong>of</strong> 5-5 g. <strong>of</strong> resorcinol and 3 g. <strong>of</strong> acetonitrile in 25 c.c. <strong>of</strong><br />
absolute ether, the mixture is kept cool in ice and saturated with<br />
hydrogen chloride. After standing for some hours in a closed vessel<br />
1 K. Hoesch, Ber., 1915, 48 .11221 1917, 50, 462.
348 QUINIZAKIN<br />
the product acquires the consistency <strong>of</strong> porridge. It is kept cool<br />
externally while 25 c.c. <strong>of</strong> ice-water are added, some ether is poured<br />
in, and the ether layer is separated. The ketimine which is present<br />
in the aqueous solution as hydrochloride is hydrolysed by boiling<br />
the solution for half an hour. The resacetophenone crystallises from<br />
the solution on cooling. Yield 4-5 g. It can be recrystallised from<br />
water or alcohol. Melting point 145°.<br />
6. QUINIZARIN FROM PHTHALIC ANHYDRIDE AND QUINOL 1<br />
A mixture <strong>of</strong> 5 g. <strong>of</strong> pure quinol, 20 g. <strong>of</strong> phthalic anhydride,<br />
50 c.c. <strong>of</strong> pure concentrated sulphuric acid, and 5 g. <strong>of</strong> boric acid is<br />
heated in an open flask on an oil bath for three hours at 150°-160°,<br />
and then for one hour at 190°-200°. While still hot the solution<br />
is stirred into a porcelain basin containing 400 c.c. <strong>of</strong> water, then<br />
heated to boiling and filtered hot at the pump. This operation is<br />
repeated, and then the precipitate is boiled with 250 c.c. <strong>of</strong> glacial<br />
acetic acid and filtered while hot at the pump. The filtrate is poured<br />
into a beaker and diluted with an equal volume <strong>of</strong> hot water. The<br />
crude quinizarin which separates on cooling is collected at the pump,<br />
washed repeatedly with water, and dried, first on the water bath and<br />
then in an oven at 120°. It is recrystallised from 150 c.c. <strong>of</strong> boiling<br />
glacial acetic acid. Melting point 194°. The substance forms large<br />
orange-yellow leaflets which, after collection at the pump, are washed<br />
with a little glacial acetic acid and then with ether. Especially fine<br />
crystals are obtained from toluene or xylene. Like alizarin, quinizarin<br />
dissolves in alkalis with a deep violet colour. It can be sublimed<br />
without decomposition. Yield 2-2-5 g.<br />
Sections 3, 4, 5, 6: Theoretical Considerations<br />
Both acid chlorides and alkyl chlorides react with aromatic compounds<br />
in the presence <strong>of</strong> aluminium chloride, zinc chloride, or ferric<br />
chloride in such a way that HC1 is eliminated and the acyl or alkyl group<br />
enters the ring :<br />
CI.CO.CH, —> r i co.cn3 +HC1<br />
+HCI<br />
1 Grimm, Ber., 1873, 6, 506 ; Baeyer, Ber., 1875, 8, 152. Liebermann, Annalen,<br />
1882, 212, 10 ; G.P. 255,031 (Friedlander, XI, 588).
THE FKIEDEL-CKAFTS KBACTION 349<br />
Whereas the first reaction, which results in the synthesis <strong>of</strong> ketones,<br />
is much used because <strong>of</strong> the ease with which it usually proceeds, the<br />
introduction <strong>of</strong> alkyl groups proves much less satisfactory since, in<br />
the first place, the substitution goes further and, in the second, the<br />
alkyl groups may at the same time be partially split <strong>of</strong>f again. The<br />
method <strong>of</strong> Fittig is usually to be preferred in this case.<br />
Under the conditions <strong>of</strong> the Friedel-Crafts reaction, substances containing<br />
an olefinic double bond react in such a way that the acid chloride<br />
is added on at this bond and a saturated j8-chlorinated ketone is formed.<br />
When heated this substance loses HC1 and yields the unsaturated ketone:<br />
\c=C— + Cl.CO.CHs —> \c—C—CO.CH3<br />
/ H / Cl H<br />
!—CO.CH3 + HCI.<br />
Hence we are justified in assuming an analogous course for the reaction<br />
in the aromatic series also (cf. Ber., 1922, 55, 2246).<br />
The function at the aluminium chloride is catalytic, and its amount<br />
is therefore independent <strong>of</strong> stoicheiometrical proportions. But since,<br />
in the ketone synthesis, a fairly definite complex addition compound<br />
with one molecule A1C13, is formed, at least one mole must be used.<br />
On account <strong>of</strong> the great reactivity <strong>of</strong> the substances taking part in<br />
the reaction, the choice <strong>of</strong> a solvent in the Friedel-Crafts synthesis is<br />
limited. The most important are carbon bisulphide, well purified petrol<br />
ether, chlorobenzene, and nitrobenzene.<br />
The method <strong>of</strong> action <strong>of</strong> the aluminium chloride is not yet clearly<br />
understood. Since with acyl and alkyl chlorides it forms complex<br />
addition products which can be isolated, it is possible that in these<br />
products the bond between the chlorine and the rest <strong>of</strong> the organic<br />
molecule is loosened, and that so the additive power is increased. It is<br />
also possible, however, that the aluminium chloride increases the reactivity<br />
<strong>of</strong> the hydrocarbon by combining with it.<br />
This holds not only for aromatic and olefinic compounds but also for<br />
cycloparaffins which likewise take part in the Friedel-Crafts reaction.<br />
In addition to the aromatic hydrocarbons, the phenolic ethers undergo<br />
this synthesis with special ease.<br />
The following individual applications may be quoted :<br />
The reaction <strong>of</strong> phthalyl chloride with benzene, leading to phthalophenone,<br />
the parent substance <strong>of</strong> the phthaleins :<br />
+ 2 HC1
350 ALDEHYDE SYNTHESES<br />
The intramolecular ketone synthesis from the chloride <strong>of</strong> hydrocinnamic<br />
acid :<br />
CH2<br />
3H2.CH2.COC1 /\/\rJT<br />
— ' Y ^ 2 +HCl.<br />
a-Hydrindone<br />
The direct synthesis <strong>of</strong> ketones from hydrocarbons and phosgene,<br />
e.g.<br />
2C6H6 + COC12 --• C6H5.CO.C6H6 + 2HC1 .<br />
The introduction <strong>of</strong> simple or substituted formamide radicles by<br />
the use <strong>of</strong> urea chlorides (cyanic acid and cyanic esters+ HC1).<br />
+ C1CONH2 >- [ || C0NH 2 + HC1 .<br />
V<br />
In this way aromatic carboxylic acids can be prepared by the<br />
Friedel-Crafts method.<br />
The range <strong>of</strong> the reaction was extended by the" elegant aldehyde<br />
synthesis <strong>of</strong> Gattermann and Koch. If a mixture <strong>of</strong> carbon monoxide<br />
and hydrogen chloride is allowed to act in the presence <strong>of</strong> aluminium<br />
chloride (and cuprous chloride) on toluene (benzene is less suitable),<br />
the reaction occurs which might be expected with formyl chloride<br />
if this substance were capable <strong>of</strong> existence.<br />
H<br />
\r C = N H , it is e v i d e n t t h a t h e r e a n a l d i m i n e is first<br />
f o r m e d a n d t h e n , w h e n t h e r e a c t i o n m i x t u r e is w o r k e d u p , is c o n v e r t e d<br />
i n t o t h e a l d e h y d e ; N H 3 is e l i m i n a t e d b y t h e a c t i o n <strong>of</strong> w a t e r . E n o l s<br />
<strong>of</strong> t h e a l i p h a t i c s e r i e s ( e t h y l a c e t o a c e t a t e , a c e t y l a c e t o n e ) r e a c t f u n d a -<br />
m e n t a l l y in t h e s a m e w a y . T h e u s e <strong>of</strong> m e r c u r y f u l m i n a t e , f r o m w h i c h<br />
b y t h e a c t i o n <strong>of</strong> h y d r o g e n c h l o r i d e t h e b e a u t i f u l l y c r y s t a l l i n e c h l o r i d e
THE FKIEDEL-CKAFTS KBACTION 351<br />
H \<br />
(C=NO)2Hg + 4 HC1 —> HgCl2 + 2 \c=NOH<br />
<strong>of</strong> formhydroxamic acid can be isolated, leads, in the aromatic series,<br />
to the formation <strong>of</strong> aldoxtm.es (Scholl).<br />
The interaction <strong>of</strong> saturated hydrocarbons with carbon monoxidealuminium<br />
chloride is <strong>of</strong> great interest. In this case the CO group is<br />
inserted into the chain, 1 e.g.<br />
CSH12 + CO —> CH3.CH2.CO.CH(CH3)2.<br />
The ketone synthesis <strong>of</strong> Houben and Hoesch, which is based on<br />
the principle <strong>of</strong> the Gattermann reaction, proceeds very smoothly and<br />
gives very favourable results, especially in the case <strong>of</strong> polyhydric phenols.<br />
In this synthesis nitriles are used. Here it is the iminochlorides<br />
R—C=NH which are converted into ketimines and then into ketones, a<br />
Cl<br />
process which is analogous to that which occurs when hydrogen cyanide<br />
is used. The formulation follows at once from what has been said.<br />
All three chlorine atoms <strong>of</strong> chlor<strong>of</strong>orm take part in the Friedel-Crafts<br />
reaction ; the product <strong>of</strong> the reaction with benzene is the important<br />
hydrocarbon triphenylmethane, the parent substance <strong>of</strong> the well-known<br />
class <strong>of</strong> dyes. Paraleucaniline, [(p) NH2.C6H4]3CH, has been converted<br />
into triphenylmethane by reductive hydrolysis <strong>of</strong> its tris-diazo-compound<br />
(E. and 0. Fischer).<br />
We might expect that the reaction would lead to the formation <strong>of</strong><br />
tetraphenylmethane from benzene and carbon telrachloride in the presence<br />
<strong>of</strong> aluminium chloride, but this is not so. In this case the fourth<br />
Cl-atom remains in the reaction product. Triphenylchloromethane<br />
(C6H5)3CC1 has acquired extraordinary importance because, when applied<br />
in the Wurtz reaction, it made possible the discovery <strong>of</strong> the first free<br />
organic radicle (Gomberg, 1900). Compare p. 352.<br />
Often in the Friedel-Crafts synthesis the acid chloride can be replaced<br />
by the anhydride. The preparation <strong>of</strong> acetophenone (p. 346)<br />
is an example <strong>of</strong> this modification.<br />
It has become especially important because <strong>of</strong> the behaviour <strong>of</strong><br />
phthalic anhydride, which can be condensed with benzene in the presence<br />
<strong>of</strong> aluminium chloride to o-benzoylbenzoic acid.<br />
Hopff, Ber., 1931, 64, 2739.
352 TKIPHBNYLMBTHYL<br />
Since, as the equation shows, this substance is converted by<br />
concentrated sulphuric acid with loss <strong>of</strong> water into anthraquinone, a<br />
very important route to a much-studied group is opened up. Thus<br />
j8-methylanthraquinone, which serves as an intermediate for valuable<br />
vat dyes, is prepared technically in this way from phthalic anhydride<br />
and toluene.<br />
Concentrated sulphuric acid here performs the same function in the<br />
first phase as does aluminium chloride, and by the use <strong>of</strong> the acid the<br />
anthraquinone derivative is obtained in a single operation. The<br />
synthesis <strong>of</strong> quinizarin, described above, provides a preparative illustration<br />
<strong>of</strong> this elegant reaction :<br />
OH OH OH<br />
Catechol, on condensation with phthalic anhydride, yields the<br />
isomeric alizarin, although in much poorer yield. The combination <strong>of</strong><br />
phthalic anhydride with pyrogallol leads to anthragallol (1:2: 3-trihydroxyanthraquinone).<br />
This substance is made on a technical scale.<br />
A complete bibliography <strong>of</strong> the literature on the Priedel-Crafts<br />
synthesis is to be found in G. Kranzlein, Aluminiumchlorid in der<br />
organischen Chemie (Verlag Chemie, 1932).<br />
ORGANIC RADICLES<br />
7. HEXAPHENYLETHANE<br />
Preparation <strong>of</strong> a Solution <strong>of</strong> Triphenylmethyl.—Pure triphenylchloromethane<br />
(2 g.) is dissolved in a glass-stoppered bottle (capacity<br />
25 c.c.) in 20 c.c. <strong>of</strong> benzene to a colourless solution. Zinc dust (5 g.)<br />
is added and the mixture is vigorously shaken for five minutes. The<br />
well-known dissociation experiment <strong>of</strong> Schmidlin is first performed<br />
with the golden-yellow or orange-yellow solution <strong>of</strong> the radicle.<br />
About 2 c.c. <strong>of</strong> the clear solution are poured into a large test tube,<br />
diluted with 2 c.c. <strong>of</strong> benzene, and shaken up. The colour disappears<br />
but soon returns again. By renewed shaking with air the radicle<br />
can again be converted into the colourless peroxide. The interesting<br />
experiment can be repeated several times. If immediate decolorisation<br />
does not occur at the first shaking, too much <strong>of</strong> the solution <strong>of</strong><br />
triphenylmethyl nas been used, and the experiment is repeated with<br />
half the quantity. The rest <strong>of</strong> the main solution is filtered through
HEXAPHENYLETHANE 353<br />
a folded paper and by shaking with air the unsaturated hydrocarbon<br />
is isolated as peroxide which separates in colourless crystals. . After<br />
standing for some time they are collected at the pump and washed<br />
with ether. Melting point (with production <strong>of</strong> red colour and decomposition)<br />
183°.<br />
Schmidlin's experiment here described shows very clearly the<br />
equilibrium between hexaphenylethane and triphenylmethyl. The<br />
disappearance <strong>of</strong> the colour on snaking the substance with air indicates<br />
that the yellow radicle, present in equilibrium, is removed as (colourless)<br />
peroxide. The re-establishment <strong>of</strong> the equilibrium by renewed dissociation<br />
<strong>of</strong> (colourless) hexaphenylethane proceeds so slowly that the<br />
formation <strong>of</strong> the yellow radicle in the decolorised solution can be<br />
observed without difficulty.<br />
As the odd number <strong>of</strong> hydrogen atoms already shows, triphenylmethyl,<br />
C19H1S, known in solution only, contains a tervalent carbon<br />
atom. In contrast to the colourless hexaphenylethane, which can be<br />
isolated in the crystalline state, triphenylmethyl is intensely yellow.<br />
Its absorption spectrum exhibits characteristic bands (examine the<br />
spectrum in a spectroscope).<br />
Triphenylmethyl is an extremely reactive substance. Its solutions<br />
are decolorised by air, which converts it into the colourless triphenylmethyl<br />
peroxide:<br />
—> (C6H5)3C.O—O.C(C6HS)3 .<br />
Halogens react in the same way :<br />
2 (C6HS)3C + Br—Br —> 2 (C6H5)3C.Br .<br />
Hydrogen chloride reacts in light to form triphenylmethane and<br />
triphenylchloromethane. The reaction is reversible (Schlenk). NO,<br />
NO2, and many organic radicles add themselves to triphenylmethyl.<br />
The combination with quinone is analogous (Schmidlin).<br />
2(C6H5)3C<br />
In addition, metallic sodium adds itself to the free valency, producing<br />
the very interesting orange-coloured, sodium triphenylmethyl<br />
(C6H5)3C.Na (Schlenk).<br />
When the molecular weight <strong>of</strong> hexaphenylethane is determined<br />
cryoscopically in benzene solution, the value corresponding to this<br />
hydrocarbon is obtained with close approximation. Indeed, only<br />
2-3 per cent <strong>of</strong> the dissolved molecules are split into the triphenylmethyl<br />
halves.<br />
The relationship<br />
O2N—NO2 ^~> 2NO2<br />
colourless brownish-red<br />
2A
354 OKGANIC KADICLES AS IONS<br />
is in many respects extraordinarily similar to the one considered<br />
here.<br />
In both cases the degree <strong>of</strong> dissociation increases with rising temperature.<br />
Ebullioscopic determination <strong>of</strong> the molecular weight shows<br />
that, in boiling benzene, 30 per cent <strong>of</strong> the substance is present as<br />
triphenylmethyl.<br />
The dissociation <strong>of</strong> hexaphenylethane can also be demonstrated<br />
colorimetrically. Whereas, in general, coloured solutions undergo no<br />
change in intensity <strong>of</strong> colour on dilution, since the number <strong>of</strong> coloured<br />
molecules observed in the colorimeter remains the same (Beer's law),<br />
the intensity must increase if the coloured molecules become more<br />
numerous as a result <strong>of</strong> progressive dissociation following dilution<br />
(Piccard).<br />
Experiments—Verify Beer's law by wrapping two test tubes in<br />
black paper, pouring the same volume (1-2 c.c.) <strong>of</strong> a dilute solution<br />
<strong>of</strong> a dye into each, and checking the equality <strong>of</strong> colour by looking<br />
down both tubes against a white surface. Then dilute the contents<br />
<strong>of</strong> one tube with 5-10 c.c. <strong>of</strong> water and again compare their colour.<br />
The decomposition <strong>of</strong> hexaphenylethane is to be attributed to the<br />
inadequate binding force between the two ethane carbon atoms which<br />
are each over-much occupied by three phenyl groups. If these are<br />
progressively replaced by diphenyl groups the combining power <strong>of</strong> the<br />
fourth valency becomes smaller and smaller, and is finally reduced to<br />
zero in -p-tridiphenyl-methyl (Schlenk).<br />
This hydrocarbon I —(~ \ ) C, indeed, exists only as a free<br />
\ \—/ \ / /3<br />
radicle, and has even been prepared as such in the solid state in the<br />
form <strong>of</strong> magnificent red-violet crystals.<br />
Of the further results <strong>of</strong> the investigation <strong>of</strong> the carbon radicles,<br />
a field still actively cultivated, only the so-called metal ketyls will be<br />
mentioned. These addition products <strong>of</strong> the alkali metals to ketones<br />
are also intensely coloured (Schlenk), e.g.<br />
(C6H5)2:C=O + Na > (C6H5)2:C—ONa .<br />
They have already been discussed on p. 224.<br />
The Triphenylmethyl Ion.—A solution <strong>of</strong> triphenylchloromethane in<br />
a dissociating solvent conducts the electric current (Walden). Since,<br />
on electrolysis, triphenylmethyl is liberated at the cathode, it follows<br />
t h a t t h e s o l u t i o n c o n t a i n s t h e i o n s ( C 6 H 5 ) 3 C a n d C l . T h e i n t e n s e l y<br />
y e l l o w s o l u t i o n o f h e x a p h e n y l e t h a n e i n l i q u i d s u l p h u r d i o x i d e a l s o c o n -<br />
d u c t s e l e c t r i c i t y , a n d h e n c e a l s o c o n t a i n s i o n i s e d t r i p h e n y l m e t h y l ( p o s -<br />
i
TBTKAPHBNYLHYDKAZINB 355<br />
sibly as a complex ion with SO2). Such a solution does not exhibit the<br />
typical band spectrum and does not react with oxygen. Consequently<br />
the sharp distinction between radicle and ion exists here in the same way<br />
as is known, for instance among the metals, between atom and ion.<br />
The triphenylmethyl ion is also, very probably, present in the orangeyellow<br />
products <strong>of</strong> the salt and complex salt type which are produced<br />
from triphenylcarbinol with concentrated sulphuric acid and from<br />
triphenylchloromethane with metallic chlorides (ZnCl2, A1C13, 8nCl4,<br />
SbClg).<br />
Experiment.-—Dissolve a few granules <strong>of</strong> triphenylcarbinol or <strong>of</strong><br />
triphenylchloromethane in 0-5 c.c. <strong>of</strong> concentrated sulphuric acid by<br />
rubbing with a glass rod. Add a little water: the deep orangeyellow<br />
solution is completely decolorised. Simultaneously the<br />
unchanged carbinol is precipitated.<br />
In the same way the above-mentioned complex salts <strong>of</strong> triphenylchloromethane<br />
are readily decomposed by water. In both cases a<br />
hydrolysis occurs which causes the triphenylmethyl ion to lose its<br />
charge, and the carbinol to be re-formed.<br />
The formation from neutral substances (triphenylcarbinol) <strong>of</strong><br />
coloured, salt-like reaction products which are more or less easily decomposed<br />
by water is a phenomenon called " halochromism ". The halochromic<br />
salts <strong>of</strong> triphenylcarbinol are regarded as carbonium salts :<br />
this follows at once from the above discussion. A quinonoid formula,<br />
by which various authors explain the colour, seems less probable.<br />
Recently the attempt has been made to attribute complex formulae to<br />
the carbonium salts (Hantzsch), in accordance with Werner's scheme<br />
for ammonium salts. Such formulae express the fact that, in the ion,<br />
the charge is not localised at the methane carbon atom, but spread over<br />
the field <strong>of</strong> force <strong>of</strong> the whole radicle. The simplest carbonium salt<br />
<strong>of</strong> the group, the yellow perchlorate (K. A. H<strong>of</strong>mann), would accordingly<br />
have the following structural formula :<br />
rc6H5.c.c6H5i OC1O<br />
L C6H5 J<br />
8. TETRAPHENYLHYDRAZINE<br />
Diphenylamine (34 g., 0-2 mole) is dissolved in 200 c.c. <strong>of</strong> pure<br />
acetone in a bottle (capacity about 400 c.c.) having a well-fitting<br />
glass or rubber stopper. (Commercial acetone is usually stable<br />
towards permanganate. If not, add powdered potassium permanganate<br />
until the colour persists even on boiling the mixture for<br />
about half an hour under reflux, then distil. Acetone so treated is
356 TBTKAPHBNYLHYDRAZINB<br />
fit for use as a solvent for oxidations. 1 ) The solution is kept cool<br />
in ice-water and vigorously shaken while very finely powdered permanganate<br />
is gradually added. Bach portion is added only after<br />
the colour produced by the preceding has disappeared. After about<br />
16 g. <strong>of</strong> permanganate have been used in the course <strong>of</strong> an hour and<br />
a half more <strong>of</strong> the oxidising agent is added without external cooling<br />
<strong>of</strong> the mixture until the colour persists for half an hour (but in<br />
no case add more than 14 g. additional permanganate). Part <strong>of</strong> the<br />
diphenylamine is oxidised down to phenylisonitrile (odour, evolution<br />
<strong>of</strong> carbon dioxide). By means <strong>of</strong> a few drops <strong>of</strong> alcohol or <strong>of</strong> formaldehyde<br />
solution the mixture is now decolorised, and the manganese<br />
dioxide, after being collected at the pump, is pressed down well<br />
and washed twice with a little warm acetone. The acetone is then<br />
distilled under slightly reduced pressure from the water bath at 35° ;<br />
if the receiver is kept cool most <strong>of</strong> the solvent can be recovered.<br />
The rest <strong>of</strong> the acetone is removed in a good vacuum at a bath<br />
temperature <strong>of</strong> 20°.<br />
To the tetraphenylhydrazine which has crystallised 20-30 c.c. <strong>of</strong><br />
ether are added with ice cooling. In this way oily material is dissolved.<br />
After some time the compound is filtered dry at the pump<br />
and washed clean with drops <strong>of</strong> ether. From 20 to 24 g. (60-70 per<br />
cent <strong>of</strong> the theoretical) <strong>of</strong> almost colourless crude product are thus<br />
obtained, which is pure enough for the following experiments. By<br />
recrystallisation from a little benzene (about two to three parts)<br />
absolutely pure tetraphenylhydrazine, melting point 144°, is obtained.<br />
The solution should be boiled for a short time only. If<br />
one-third <strong>of</strong> its volume <strong>of</strong> boiling alcohol is added with shaking to the<br />
hot solution, more crystallises than from benzene alone. The pure<br />
preparation is collected at the pump, washed, first with benzenealcohol<br />
1:1, then with alcohol alone, and immediately dried in a<br />
vacuum desiccator. The mother liquor may be evaporated in vacuo<br />
and the residue digested with cold ether as before. When pure and<br />
well dried the substance can be preserved unchanged for years if<br />
protected from light and acids.<br />
Experiment,—Dissolve about 0-5 g. <strong>of</strong> tetraphenylhydrazine in<br />
5 c.c. <strong>of</strong> xylene and warm the solution slowly over a small flame.<br />
The initially colourless solution becomes intensely olive green, even<br />
before the boiling point <strong>of</strong> the solvent is reached. The colour is that<br />
<strong>of</strong> the free radicle which, at this temperature, very rapidly under-<br />
1 Cf. F. Sachs, Ber., 1901, 34, 497.
FIXATION OF DIPHENYLNITKOGEN 357<br />
goes further alteration, but, as the next experiments show, can be<br />
fixed as diphenylnitrosamine if nitric oxide is present.<br />
Experiment.-—Pour concentrated sulphuric acid on to a few centigrammes<br />
<strong>of</strong> tetraphenylhydrazine. A beautiful red colour at first<br />
appears ; it changes in a short time to intense blue-violet.<br />
The dye which is formed here is identical with that which is produced<br />
from diphenylamine in the well-known test for nitric acid (and<br />
other oxidising agents), namely, diphenyldiphenoquinone-dhmonium<br />
sulphate) (Kehrmann).<br />
H<br />
OSO3H<br />
When the dye is formed from tetraphenylhydrazine, diphenylhydroxylamine<br />
(pp. 182, 341) is first produced by hydrolysis at the<br />
N—N-linkage.<br />
THE FIXATION OF DIPHENYLNITROGEN BY NITRIC OXIDE 1<br />
An apparatus for producing pure nitric oxide is set up as follows.<br />
As in the apparatus for preparing hydrogen chloride, a filter flask<br />
(capacity 750 c.c.) is fitted with a dropping funnel, from which 4Nsulphuric<br />
acid is dropped into concentrated sodium nitrite solution,<br />
containing 70 g. <strong>of</strong> NaN02 in 150 c.c. <strong>of</strong> water. For this amount <strong>of</strong><br />
nitrite 250 c.c. <strong>of</strong> the 4iV-acid are required. The side tube <strong>of</strong> the<br />
flask leads first to a wash-bottle with concentrated sodium (or<br />
potassium) hydroxide, and then to one with concentrated sulphuric<br />
acid. By means <strong>of</strong> a short rubber tube a T-tube is attached to the<br />
second wash-bottle. One branch <strong>of</strong> the tube is connected to a<br />
carbon dioxide Kipp, the other to the reaction vessel. The rubber<br />
tube carries a screw clip so that, at the end <strong>of</strong> the experiment, the<br />
nitric oxide generator can be removed.<br />
Tetraphenylhydrazine (5 g.) is dissolved in 40 c.c. <strong>of</strong> toluene in a<br />
small round-bottomed flask fitted with a two-holed cork. A delivery<br />
tube, which is connected to the apparatus just described and<br />
reaches to the bottom <strong>of</strong> the flask, passes through one hole, a short<br />
glass tube through the other. With the second wash-bottle disconnected<br />
from the rubber tube, and the latter closed by means <strong>of</strong><br />
the clip, the dropping in <strong>of</strong> sulphuric acid is begun, and at the same<br />
1 Annalen, 1911, 381, 211.
358 BIVALENT NITKOGBN<br />
time the air in the other part <strong>of</strong> the apparatus and the reaction vessel<br />
is driven out by carbon dioxide. The flask is clamped in such a<br />
position that, immediately afterwards, it can be placed on a vigorously<br />
boiling water bath kept ready for the purpose. When all the<br />
air in the first part <strong>of</strong> the apparatus has been expelled by nitric<br />
oxide, i.e. when the gas in the exit tube <strong>of</strong> the second wash-bottle<br />
has become quite colourless, the two parts <strong>of</strong> the apparatus are<br />
rapidly connected by means <strong>of</strong> the rubber tube, the clip is unscrewed,<br />
and the nitric oxide, accompanied by a gentle current <strong>of</strong> carbon<br />
dioxide, is passed into the flask. As soon as brown fumes (N02)<br />
begin to escape from its exit tube the flask is placed on the boiling<br />
water bath and a rather rapid stream <strong>of</strong> nitric oxide is passed into<br />
the toluene solution for half an hour. At the end <strong>of</strong> this time the<br />
solution is yellow. The flame under the bath is now lowered, the<br />
clip screwed down, the nitric oxide generator disconnected, and all<br />
the nitric oxide which remains in the rest <strong>of</strong> the apparatus is driven<br />
out by a brisk current <strong>of</strong> carbon dioxide (test with potassium iodidestarch<br />
paper). Then the toluene is completely removed by distillation<br />
in a vacuum, and the crystalline diphenylnitrosamine which<br />
remains is purified by recrystallisation from a little alcohol or from<br />
petrol ether. Melting point 66°.<br />
Experiments—In order to show that this formation <strong>of</strong> aromatic<br />
nitrosamines is reversible, boil a small amount <strong>of</strong> the pure compound<br />
just prepared in xylene and hold a piece <strong>of</strong> moist potassium iodidestarch<br />
paper over the mouth <strong>of</strong> the tube.<br />
A close analogy to the carbon radicles is provided by certain nitrogen<br />
compounds, which are likewise free unsaturated complexes partaking<br />
<strong>of</strong> the character <strong>of</strong> atoms and having an abnormal valency. With<br />
nitrogen, as with carbon, the existence <strong>of</strong> radicles also depends on the<br />
presence <strong>of</strong> aromatic rings. Tetraphenylhydrazine corresponds to hexaphenylethane.<br />
The linkage between the two N-atoms is here firmer than in the<br />
carbon prototype. Dissociation into the diphenylnitrogen radicles in<br />
solution is not perceptible to the eye below about 80° :<br />
(H5C6)2N-N(C6H5)2 —• 2(C^S),N.<br />
However, if positive substituents are introduced into the benzene<br />
rings, hydrazine derivatives result which considerably surpass hexaphenylethane<br />
in their degree <strong>of</strong> dissociation. Already the colourless<br />
ip-tetra-anisylhydrazine is appreciably dissociated at room temperature<br />
into the green -p-dianisylnitrogen radicles (H3CO.C6H4)2N and the corre-
QUADKIVALBNT NITROGEN 359<br />
sponding hydrazine containing four —N(CH3)2-groups instead <strong>of</strong> four<br />
methoxy groups is dissociated into the yellow bis-j>-dimethylaminodiphenylnitrogen<br />
[(CHg^N.CgH^N radicles,in cold benzene to the extent<br />
<strong>of</strong> 10 per cent, in nitrobenzene to the extent <strong>of</strong> 21 per cent.<br />
In contrast to their inorganic prototype, nitric oxide, these radicles<br />
are not sensitive towards oxygen. On the other hand they take up<br />
nitric oxide with great ease, so that this property is <strong>of</strong> general use for<br />
their recognition.<br />
(C6H5)2N + NO —• (C6HS)2N.NO.<br />
It will be noticed that by this reaction the nitrosamines <strong>of</strong> the corresponding<br />
diarylamines are formed. The nitrogen radicles also combine<br />
with triphenylmethyl and other radicles, with mutual saturation <strong>of</strong> the<br />
free valencies.<br />
(C6H5)2N + (C6H5)3C —> (C6H6)2N-C(C6H5)3.<br />
As-regards stability, the nitrogen radicles are inferior to those <strong>of</strong><br />
carbon. They undergo a change which is observed throughout this<br />
division <strong>of</strong> chemistry. It consists in dismutation, i.e. the normal degree<br />
<strong>of</strong> saturation is restored by the removal, by one molecule, <strong>of</strong> an atom <strong>of</strong><br />
hydrogen from the other. Along with the secondary amine a product<br />
poorer in hydrogen is formed, namely, a phenzine derivative.<br />
2 (H3CO.C6H4)2N —> (H3CO.C6H4)2NH + (H3CO.C6H4)2NlessH<br />
2 [(H3CO.C6H4)2N less 1 H] —><br />
H3C<br />
The hydrogen has therefore been taken from the positions marked<br />
with the asterisks. The simplest example <strong>of</strong> this dismutation <strong>of</strong> radicles<br />
occurs in the hydroxyl radicles, resulting from the discharge <strong>of</strong> the<br />
hydroxyl ion.<br />
2 OH —> HOH + 0 ; 2 0 —> O2 .<br />
Mention should also be made <strong>of</strong> radicles with bivalent nitrogen<br />
which are derived from hydrazines, the so-called hydrazyls. They are<br />
deeply coloured compounds which are obtained by dehydrogenation <strong>of</strong><br />
tertiary hydrazines and form equilibrium mixtures with colourless<br />
tetrazanes, which dissociate into these free radicles (S. Goldschmidt),<br />
T^ N.N(C6H5)2 2 (C6H5)2N-N.C6H5<br />
CftHe CftHc
360 QUADKIVALBNT NITROGEN<br />
The radicle NO2 also lias an analogue in the aromatic series.<br />
When diphenylhydroxylamine is dehydrogenated with silver oxide<br />
the beautifully crystalline garnet-red diphenylnitrogen oxide is formed :<br />
HO-N(C6H5)2 —> O=N(C6H5)2.<br />
This compound is surprisingly similar to NO2, not only in colour, but<br />
also in many reactions. It, however, lacks all tendency to lose the<br />
radicle state and to dimerise like nitrogen peroxide.. In this respect it<br />
resembles nitric oxide, whereas the organic relatives <strong>of</strong> nitric oxide are<br />
more like nitrogen peroxide.<br />
The subject <strong>of</strong> free radicles is fully dealt with by P. Walden in<br />
Chemie derfreien Radikale, Leipzig, 1924.
CHAPTBK X<br />
HETEEOCYCLIC COMPOUNDS<br />
1. PYRIDINE DERIVATIVES<br />
(a) HANTZSCH'S COLLIDINE SYNTHESIS 1<br />
Ethyl Dihydrocollidinedicarboxylate.—A mixture <strong>of</strong> 33 g. <strong>of</strong> ethyl<br />
acetoacetate and 10 g. <strong>of</strong> aldehyde ammonia is heated in a small<br />
beaker on a wire gauze for three minutes at 100°-110°. During that<br />
time the mixture is stirred with a thermometer. Two volumes <strong>of</strong><br />
2 iy-hydrochloric acid are then added to the warm reaction product,<br />
which is vigorously stirred without further heating until the initially<br />
liquid mass has solidified. The solid is now finely ground in a<br />
mortar, collected at the pump, washed with water, and dried on<br />
porous plate. The crude material can be used directly for further<br />
treatment. A sample, recrystallised from a little alcohol, forms<br />
colourless plates having a bluish fluorescence. Melting point<br />
131°.<br />
Ethyl Collidinedicarboxylate.—The crude ester is mixed with an<br />
equal weight <strong>of</strong> alcohol, the mixture is kept cool in water, and gaseous<br />
nitrous acid 2 is passed in until the dihydro ester has dissolved and<br />
a sample <strong>of</strong> the liquid forms a clear solution in dilute hydrochloric<br />
acid.<br />
The solution is now poured and rinsed into a moderate-sized<br />
(500-750 c.c.) separating funnel containing 100 g. <strong>of</strong> ice, and the acid<br />
is buffered by slowly adding finely powdered sodium carbonate.<br />
The ester separates as an oil and is taken up in ether, but the funnel<br />
must not be stoppered and shaken until evolution <strong>of</strong> carbon dioxide<br />
has ceased. Extraction with ether is repeated and the combined<br />
1 AnnaUn, 1882, 215, 1.<br />
2 Cautiously powder 50 g. <strong>of</strong> arsenious oxide and treat with a mixture <strong>of</strong> 75 c.c.<br />
<strong>of</strong> concentrated nitric acid (d. = 1-4) with 30 c.c. <strong>of</strong> water in a round-bottomed flask.<br />
The acid is run in slowly through a dropping funnel passing through the two-holed<br />
cork ; the delivery tube passes through the other hole and is connected to an empty<br />
wash-bottle. Heat the flask gently on a wire gauze.<br />
361
362 HANTZSCH'S COLLIDINB SYNTHESIS<br />
extracts, after being shaken again with water in order to remove<br />
most <strong>of</strong> the alcohol, are dried for a short time with potassium carbonate.<br />
The ether is then evaporated and the residue is distilled in<br />
a vacuum. Boiling point 175°-178°/12 mm. Yield 15 g. <strong>of</strong> ester<br />
<strong>of</strong> collidine dicarboxylic acid from 20 g. <strong>of</strong> dihydro-ester.<br />
Potassium Collidinedicarboxylate.—Purified potassium hydroxide<br />
(30 g.) is dissolved in 100 c.c. <strong>of</strong> absolute alcohol by boiling for a long<br />
time in a round-bottomed flask (capacity 250 c.c.) under reflux on a<br />
wire gauze, 15 g. <strong>of</strong> ethyl collidinedicarboxylate are added, and the<br />
solution is refluxed for three to four hours on a vigorously boiling<br />
water bath. The salt produced is sparingly soluble in alcohol and<br />
gradually separates in the form <strong>of</strong> a crystalline crust. When the<br />
hydrolysis is over the crystals are separated from the cooled solution<br />
at the pump and washed, first twice with alcohol and then with<br />
ether. Yield 12-14 g.<br />
Collidine.—The carboxyl group is removed by heating the potassium<br />
salt with slaked lime. The salt is thoroughly mixed with twice<br />
its weight <strong>of</strong> calcium hydroxide by grinding in a mortar, and the<br />
mixture is poured into a combustion tube (about 60 cm. long)<br />
closed 10 c.c. from the end with an asbestos plug. By means <strong>of</strong><br />
another loosely fitting asbestos plug the mixture is kept in position<br />
and one end <strong>of</strong> the tube is tightly corked. The other end is connected<br />
with a receiver by means <strong>of</strong> an adapter and the tube is placed<br />
with the closed end uppermost in an inclined combustion furnace.<br />
After a moderately deep channel has been produced over the mixture by<br />
tapping the tube is warmed by small flames. Then, beginning at<br />
the elevated end <strong>of</strong> the tube, the flames are raised more and more<br />
until, with closed tiles, a bright red heat is finally reached. The<br />
collidine which distils is dissolved in ether, and the solution dried<br />
with a little potassium hydroxide ; the ether is evaporated and the<br />
collidine distilled. Boiling point 172°. Yield 3-4 g.<br />
If a nitrogen cylinder is available, the mixture <strong>of</strong> potassium salt<br />
and lime is heated in a slow stream <strong>of</strong> the gas.<br />
The synthesis <strong>of</strong> the pyridine ring from ethyl acetoacetate, aldehydes,<br />
and ammonia proceeds extraordinarily readily. The mechanism is as<br />
follows. In the first phase the aldehydes react with the acetoacetic<br />
ester to form alkylidene bis-acetoacetic esters. The 1 : 5-diketone derivatives<br />
so formed undergo ring closure by introduction <strong>of</strong> a molecule <strong>of</strong><br />
ammonia and elimination <strong>of</strong> two molecules <strong>of</strong> water :
KNOEVENAGEL'S SYNTHESIS<br />
E<br />
JH<br />
II /-<br />
EOOC.CH2 0 H2C.COOE EOOC.C<br />
C.COOE<br />
I | —• II II II<br />
HgC.CO OC.CH3 HgC.COH HOC.CHg<br />
NH3<br />
E<br />
EOOC.C C.COOE<br />
HgC.C<br />
I<br />
C.CH3<br />
E<br />
363<br />
NH<br />
If the synthesis is carried out without ammonia the six-ring synthesis<br />
<strong>of</strong> Knoevenagel takes place. This synthesis, which is catalytically<br />
induced by bases such as diethylamine and piperidine, consists in<br />
ring closure <strong>of</strong> the intermediate product, <strong>of</strong> which the di-enol form is<br />
shown above.<br />
E E<br />
EOOC.CH CH.COOE EOOC.CH<br />
CH.COOE<br />
I I<br />
HgC.CO CO<br />
H3C.C CO<br />
\ /<br />
H,C<br />
CH<br />
In Hantzsch's synthesis the condensation product is a derivative <strong>of</strong><br />
dihydro'pjn^ine and is only converted into a true pyridine derivative<br />
by dehydrogenation. It is only by the removal <strong>of</strong> the two hydrogen<br />
atoms in the 1 : 4-positions that the heterocyclic ring system analogous<br />
to benzene is produced. The corresponding conversion <strong>of</strong> ethyl A 2 : 5dihydroterephthalate<br />
into ethyl terephthalate takes place much more<br />
readily.<br />
E<br />
CH<br />
—c c—<br />
II II<br />
—C C—<br />
NH<br />
E<br />
C<br />
/X<br />
—C C-<br />
II I<br />
—C C-<br />
Y<br />
CH<br />
COOE COOE<br />
^_<br />
OOE COOE
364 THE HOFMANN AND VON BKAUN DBGKADATIONS<br />
That the true pyridine derivative is more basic than the dihydrocompound<br />
is connected with the fact that in the latter the NH-group<br />
is united to two doubly bound C-atoms. Yet also pyridine and its<br />
derivatives are but weak bases.<br />
Pyridine (and quinoline) which in so many respects are " aromatic "<br />
and comparable to benzene, lose this character completely on hydrogenation<br />
to piperidine (and hydroquinoline), which are entirely <strong>of</strong> the<br />
same nature as secondary aliphatic amines. The completely hydrogenated<br />
heterocyclic bases undergo degradation reactions which have<br />
become important particularly in the investigation <strong>of</strong> the constitution<br />
<strong>of</strong> alkaloids. A. W. H<strong>of</strong>mann's method <strong>of</strong> opening rings by means<br />
<strong>of</strong> " exhaustive methylation " may be illustrated with piperidine. By<br />
thermal decomposition <strong>of</strong> the quaternary ammonium base a C—N-linkage<br />
is broken and at the same time water is eliminated.<br />
OH, OH,<br />
CH2 CH2 CH CHjj<br />
I I - + II I +H2O.<br />
CH2 CH2 ^-^-2 ^-^-2<br />
HON:(CH3)2<br />
The open-chain unsaturated tertiary amine is again exhaustively<br />
methylated and its quaternary ammonium base, in its turn, decomposed<br />
as before.<br />
CH, CH,<br />
IM<br />
CH CH2 CH CH<br />
- • - + || || +N(CH3)a<br />
(H3C)3NOH CH,.CH=CH.CH=CH,<br />
In this way piperidine is converted into the hydrocarbon " piperylene<br />
", a-methylbutadiene. The cause <strong>of</strong> the shift in the double bond<br />
is the same as in the rearrangement <strong>of</strong> eugenol to isoeugenol and <strong>of</strong><br />
j8- to a-dihydromwonic acid. Formulate this degradation reaction<br />
with ft-methylpyrrolidine.<br />
A second method is due to J. von Braun and consists in the addition<br />
<strong>of</strong> cyanogen bromide to tertiary cyclic bases. 1 In the unstable addition<br />
product a C—N-linkage is broken and at the same time the bromine<br />
wanders to a new position. A brominated derivative <strong>of</strong> cyanamide<br />
is produced and this, on hydrolysis, yields a secondary amine which can<br />
be broken down further, e.g.<br />
1 Ber., 1907, 40, 39U ; 1909, 42, 2219 ; 1911, 44, 1252.
a-AMINOPYKIDINB 365<br />
rH2<br />
I 2 I -+ I ' I -+ I " |" +NC.C6HS.<br />
CH2 CH2 CH2 CH2 CICH2CICH2<br />
N.CO.C6H5<br />
N.C(C1)2.C6HS<br />
CN<br />
(6) a-AMINOPYRIDINE !<br />
Sodamide (10 g.) is ground under xylene in a mortar and added<br />
to 16 g. (0-2 mole) <strong>of</strong> pyridine which has been dried over powdered<br />
potassium hydroxide or barium oxide, distilled, and mixed with<br />
30 c.c. <strong>of</strong> sodium-dried xylene. The mixture is then heated under<br />
reflux in an oil bath at 14O°-150° for seven hours. Moisture must<br />
be completely excluded. After cooling, 20 c.c. <strong>of</strong> cooled sodium carbonate<br />
solution are gradually and cautiously added, the mixture is<br />
shaken up, and the layers <strong>of</strong> liquid are then separated with a funnel.<br />
The aqueous layer is extracted several times with benzene; the<br />
extracts are combined and dried for a short time over solid potassium<br />
hydroxide ; the solvents are removed by distillation. For purification<br />
the high-boiling aminopyridine is distilled hi a vacuum (sausage<br />
flask); the first portion <strong>of</strong> the distillate consists chiefly <strong>of</strong> xylene.<br />
The base boils at 93°/ll mm. and 96°/13 mm. Yield 6-7 g. A<br />
further small amount can be obtained from the first and last portions<br />
<strong>of</strong> the distillate by fractionation. a-Aminopyridine crystallises easily<br />
and can be recrystallised from ligroin. Melting point 57°.<br />
1 Tschitschibabin, Chem. Zentr., 1915, I, 1065 ; Wibaut, Bee. trav. chim., 1923,<br />
42, 240.
366 QUINOLINB<br />
The very remarkable reaction which consists in the introduction<br />
<strong>of</strong> the NH2-group into an aromatic ring by the action <strong>of</strong> sodamide is<br />
due to F. Sachs (Ber., 1906, 39, 3006), who studied various examples <strong>of</strong><br />
the process in the naphthalene and anthraquinone series.<br />
In the case <strong>of</strong> pyridine, Tschitschibabin's synthesis proceeds with<br />
special ease. An intermediate addition product <strong>of</strong> NH2Na to the<br />
—N=C double bond with the grouping —NNa—C(NH2)— is doubtless<br />
formed. The net result is as follows :<br />
C5H5N + NaNH2<br />
> CSH4N.NH2 + Na + H ,<br />
and the a-aminopyridine thus formed behaves, in its reactions, like a<br />
tautomeric compound. Many <strong>of</strong> its derivatives, especially the cyclic<br />
ones, are derived from a diimino-form which can arise as a result <strong>of</strong> the<br />
following rearrangement:<br />
2. QUINOLINE<br />
(a) SKRAUP'S QUINOLINE SYNTHESIS 1<br />
Concentrated sulphuric acid (45 c.c.) is poured with shaking into<br />
a flask (capacity 1-5 1.) containing a mixture <strong>of</strong> 20 g. <strong>of</strong> nitrobenzene,<br />
31 g. <strong>of</strong> aniline, and 100 g. <strong>of</strong> anhydrous 2 glycerol. The flask is then<br />
fitted with a long wide reflux condenser and heated on a wire gauze.<br />
As soon as the sudden escape <strong>of</strong> bubbles <strong>of</strong> vapour from the liquid<br />
shows that the reaction has set in, the flame is immediately removed,<br />
and the main reaction, 3 which is sometimes extremely violent, is<br />
allowed to proceed to completion without external heating. When<br />
the reaction has subsided the mixture is kept boiling for three hours<br />
more on a wire gauze or sand bath, then a little water is added and<br />
the unchanged nitrobenzene is completely removed from the acid<br />
liquid by a current <strong>of</strong> steam. While still warm the liquid in the<br />
flask is made alkaline with concentrated sodium hydroxide, and<br />
1 Monatsh., 1880, 1, 316 ; 1881, 2, 139. M. Wyler, Ber., 1927, 60, 398. Darzens,<br />
Bull. Soc. Mm., 1930, 47, 227.<br />
2 Heat commercial glycerol in a porcelain basin in the fume chamber until a<br />
thermometer hung with the bulb in the liquid registers 180°.<br />
a The main reaction can be moderated by adding only half <strong>of</strong> the sulphuric acid<br />
at the beginning, heating cautiously to gentle boiling with a small flame, and, after<br />
one hour, adding the remainder <strong>of</strong> the acid quite slowly drop by drop. The mixture<br />
is then kept boiling as above for three hours more.
QUINALDINB 367<br />
the liberated quinoline, along with unchanged aniline, is likewise<br />
distilled with steam. The distillate is extracted with ether, the ether<br />
is evaporated, and the crude bases are dissolved in a mixture <strong>of</strong> 50<br />
c.c. <strong>of</strong> concentrated hydrochloric acid with 200 c.c. <strong>of</strong> water. After<br />
warming the clear solution so obtained, 30 g. <strong>of</strong> zinc chloride in 50<br />
c.c. <strong>of</strong> 2 i^-hydrochloric acid are added. A quinoline-zinc chloride<br />
double salt crystallises as the solution cools, and after the mixture<br />
has been left in ice for some time the crystals are collected at the<br />
pump, washed with cold 2 i\f-hydrochloric acid, and decomposed with<br />
concentrated sodium hydroxide solution. Once more the quinoline<br />
is distilled in steam, extracted from the distillate with ether, dried in<br />
the ethereal solution with solid potassium hydroxide, and ultimately<br />
distilled after the ether has been evaporated. Boiling point 237°.<br />
Yield 24-25 g. The preparation is water-clear.<br />
(6) QUINALDINE SYNTHESIS OF DOEBNER AND MILLER 1<br />
To a mixture <strong>of</strong> aniline (31 g.) and commercial concentrated<br />
hydrochloric acid (60 c.c.) in a one-litre flask, 45 c.c. <strong>of</strong> paraldehyde<br />
are added (or 60 c.c. <strong>of</strong> acetaldehyde carefully dropped in through<br />
a long reflux condenser, while the flask is cooled in ice). The mixture<br />
is left at room temperature ; the condensation takes place gradually<br />
with slight evolution <strong>of</strong> heat. The liquid is then boiled under reflux<br />
for three hours, made strongly alkaline with sodium hydroxide, and<br />
submitted to steam distillation. From the distillate the crude base<br />
is extracted with ether and the extract is dried with solid potassium<br />
hydroxide. After the ether has been evaporated unchanged aniline<br />
is removed by boiling under reflux for a quarter <strong>of</strong> an hour with 10 c.c.<br />
<strong>of</strong> acetic anhydride, cooling, making distinctly alkaline with saturated<br />
sodium carbonate solution, and distilling again with steam.<br />
After working up in the usual way the quinaldine is purified by distillation<br />
in a vacuum. Boiling point 115°-120°/l2 mm. The last portion<br />
<strong>of</strong> the distillate consists <strong>of</strong> a small amount <strong>of</strong> bases <strong>of</strong> higher boiling<br />
points. Yield 18-20 g.<br />
The quinaldine can also be separated from the crude mixture <strong>of</strong><br />
bases by conversion into the zinc chloride double salt in the manner<br />
described in the case <strong>of</strong> quinoline. This furnishes a somewhat<br />
smaller yield <strong>of</strong> a purer preparation.<br />
i Ber., 1881, 14, 2816; 1883, 16, 1664 j 1884, 17, 1712.
368 MECHANISM OF SKKAUP'S KBACTION<br />
The first quinoline derivative obtained by the process (a) was the<br />
dye alizarin blue (Prud'homme, 1877). /3-Nitroalizarin was heated<br />
with glycerol and sulphuric acid. The constitution <strong>of</strong> the product was<br />
established by Graebe :<br />
CO OH CO OH<br />
D u r i n g t h e p r o c e s s t h e N O 2 - g r o u p i s r e d u c e d t o N H 2 .<br />
--»•<br />
S k r a u p ' s s y n t h e s i s i n v o l v e s t h e e l i m i n a t i o n o f w a t e r . T h u s a c r o l e i n<br />
w i l l b e f o r m e d . I t m a y r e a c t w i t h a n i l i n e t o f o r m a n a z o m e t h i n e<br />
( S c h i f l ' s b a s e ) ( I ) , b u t m o r e p r o b a b l y t h e b a s e a d d s i t s e l f t o t h e O = C<br />
d o u b l e b o n d ( I I ) :<br />
. N H<br />
N N<br />
O n e i t h e r h y p o t h e s i s a d i h y d r o q u i n o l i n e i s f o r m e d . T h e e x t r a<br />
h y d r o g e n i s r e m o v e d b y t h e n i t r o b e n z e n e p r e s e n t .<br />
A s e c o n d s i m i l a r s y n t h e s i s , d u e t o D o e b n e r a n d M i l l e r , l e a d s t o t h e<br />
f o r m a t i o n o f s u b s t i t u t e d q u i n o l i n e s . T h e s i m p l e s t e x a m p l e i s t h e p r o -<br />
d u c t i o n o f q u i n a l d i n e f r o m a n i l i n e a n d p a r a l d e h y d e b y h e a t i n g w i t h<br />
c o n c e n t r a t e d h y d r o c h l o r i c a c i d . T h e c o u r s e o f t h e r e a c t i o n i s c l o s e l y<br />
r e l a t e d t o t h a t o f t h e S k r a u p s y n t h e s i s b y r o u t e I I . T h e r e t h e a n i l i n e<br />
r e a c t s w i t h a c r o l e i n , h e r e w i t h c r o t o n a l d e h y d e , w h i c h i s e a s i l y f o r m e d<br />
u n d e r t h e c o n d i t i o n s w h i c h p r e v a i l :<br />
N H , N H N H<br />
i C H . C H 3<br />
j i C H<br />
H O C O H<br />
H e r e a l s o t h e r e a r e t w o h y d r o g e n a t o m s i n e x c e s s , b u t t h e y a r e<br />
r e m o v e d b y s e c o n d a r y r e a c t i o n s ( l e a d i n g t o t h e f o r m a t i o n o f h y d r o -<br />
g e n a t e d p r o d u c t s ) . T h e w e l l - k n o w n d r u g a t o p h a n ( u s e d i n g o u t ) ,
ATOPHAN. PHENYLGLYCINE 369<br />
a-phenylquinoline-y-carboxylic acid, is the product <strong>of</strong> an analogous<br />
condensation <strong>of</strong> aniline with benzaldehyde and pyruvic acid :<br />
NH2<br />
N<br />
O:CH.C6H5 -+ /\/\c.C6Hs<br />
O:C."COOH C.COOH<br />
Atophan can also be obtained by alkaline condensation <strong>of</strong> isatin<br />
with acetophenone. (Formulate.)<br />
The CH3-group in quinaldine, like that <strong>of</strong> ketones, can condense<br />
with aldehydes and similar substances. With phthalic anhydride<br />
the yellow dye quinophthalone is formed.<br />
3. INDIGO<br />
Phenylglycine. 1 —Chloroacetic acid (19 g.) is exactly neutralised in<br />
the cold with 100 c.c. <strong>of</strong> 2i\f-sodium hydroxide solution, 18-6 g. <strong>of</strong><br />
aniline are added, and the mixture is boiled for a short time under<br />
reflux until the aniline has reacted and dissolved. On cooling, the<br />
phenylglycine separates as an oil which soon crystallises when<br />
rubbed. The crystalline material is kept cool in ice for some time,<br />
collected at the pump, and washed with a little ice-cold water.<br />
Yield 22-24 g. <strong>of</strong> dry substance.<br />
In order to prepare the potassium salt, 20 g. <strong>of</strong> phenylglycine<br />
are made exactly neutral to phenolphthalein with 2 i\f-potassium<br />
hydroxide solution (about 70 c.c. are required), and the clear solution<br />
is then evaporated to dryness on the water bath. For the indoxyl<br />
fusion the residue <strong>of</strong> salt must be dried in an oven at 100° for several<br />
hours.<br />
Indoxyl Fusion. 2 —A mixture <strong>of</strong> 15 g. <strong>of</strong> sodium hydroxide and<br />
20 g. <strong>of</strong> potassium hydroxide is fused and carefully dehydrated by<br />
heating to about 500° in a nickel crucible. When the mass has<br />
barely solidified it is just remelted by gentle heating and poured into<br />
a Jena glass conical flask (capacity 100 c.c.) which is at a temperature<br />
<strong>of</strong> 220° in an oil bath. If this procedure is adopted there need be no<br />
fear that the glass will crack.<br />
Sodamide (10 g.) is added to the melt in the flask and dissolves<br />
with slight evolution <strong>of</strong> ammonia. The pure potassium phenylglycine<br />
(20 g.) which has been completely dried at 100° in an oven is<br />
1 J. Houben, Ber., 1913, 47, 3988.<br />
2 According to directions supplied by Dr. J. Pfleger, Frankfurt a. M.<br />
2B
370 INDIGO<br />
then introduced in spoonfuls during the course <strong>of</strong> five to ten minutes<br />
with cautious stirring by means <strong>of</strong> a glass rod. (Byes and hands<br />
must be protected.) The temperature <strong>of</strong> the bath is maintained at<br />
200°-220°. Two minutes after the last portion <strong>of</strong> potassium salt has<br />
been added, the flask, which has been loosely stoppered with a cork,<br />
is removed from the bath and left to cool. • When quite cold the<br />
flask is broken up and the melt, in small pieces, is dissolved in 500 c.c.<br />
<strong>of</strong> water in a beaker (capacity 11.). The liquid is poured rapidly<br />
through a large folded filter into a round-bottomed flask or filter<br />
flask 1 (capacity 1-5 1.), and air is drawn through the solution by<br />
means <strong>of</strong> a water pump until a drop <strong>of</strong> the aqueous suspension <strong>of</strong><br />
indigo, placed on filter paper, produces a sharply defined ring <strong>of</strong> precipitated<br />
indigo, outside which the liquid no longer becomes blue<br />
on exposure to the air.<br />
After oxidation has thus been completed the indigo is collected<br />
at the pump, washed with hot water, transferred to a beaker by<br />
means <strong>of</strong> a jet <strong>of</strong> water, boiled with 10 per cent hydrochloric acid,<br />
again collected at the pump, washed with hot water, and dried. The<br />
yield reaches 60 to 70 per cent <strong>of</strong> the theoretical.<br />
A simple qualitative test <strong>of</strong> the purity <strong>of</strong> the indigo obtained can<br />
be carried out as follows : A little <strong>of</strong> the material is heated for some<br />
time (with shaking) in a test tube with pyridine and some drops <strong>of</strong><br />
the liquid are then poured on to a filter paper. If the indigotin is<br />
pure the pyridine is not coloured, whereas impurities which may be<br />
formed when working on a small scale confer on it a more or less<br />
dirty brown colour, as shown by a " spot " test. If it is desired to<br />
purify the whole <strong>of</strong> the indigo with pyridine, the dye is collected at<br />
the pump after boiling with the liquid, washed with pure hot pyridine,<br />
boiled once more with hydrochloric acid, collected at the pump,<br />
washed with hot water, and dried. 2<br />
The synthesis <strong>of</strong> indigo given here is the one now usually employed<br />
on a technical scale; it shows how the dye is ultimately made from<br />
coke and lime (yielding acetic acid via acetylene), chlorine and aniline,<br />
The cultivation <strong>of</strong> indigo-yielding plants has thus become unnecessary,<br />
although the biological method <strong>of</strong> production has not yet suffered the<br />
same fate as befell the cultivation <strong>of</strong> madder through the synthesis <strong>of</strong><br />
alizarin.<br />
The synthesis <strong>of</strong> indigo by means <strong>of</strong> alkaline fusion <strong>of</strong> phenylglycine<br />
1 Filtration ia not absolutely essential, but yields a purer product.<br />
a G. P. 134,139. Hochst Dye Works.
INDIGO FKOM o-NITKOBBNZALDBHYDB 371<br />
was discovered by Heumann as early as 1892, but a satisfactory yield<br />
was only obtained through the addition <strong>of</strong> sodamide (J. Pfleger).<br />
The constitution <strong>of</strong> the dye was first elucidated by the classical<br />
researches <strong>of</strong> A. Baeyer. The numerous syntheses cannot here be<br />
discussed in detail; only the most elegant, which was indeed employed<br />
for some time on a technical scale, can be described. 1<br />
In this process o-nitrobenzaldehyde is condensed in alkaline solution<br />
with acetone. The so-called o-nitrophenyllactic acid ketone thus formed<br />
loses acetic acid, and by further loss <strong>of</strong> a molecule <strong>of</strong> water is changed<br />
into indolone, which corresponds to half <strong>of</strong> the indigo molecule. Possibly<br />
o-nitrostyrene is an intermediate stage in this transformation. Indolone<br />
cannot exist in the free state, and hence polymerises at once to<br />
the dye:<br />
CHOH<br />
The transfer <strong>of</strong> the oxygen from a nitro-group to a carbon atom in<br />
the or^o-position may not seem very likely, but several similar reactions<br />
are known. Thus o-nitrotoluene is converted by alkali into anthranilic<br />
acid (Binz), o-nitrobenzaldehyde by sunlight into o-nitrosobenzoic acid<br />
(Ciamician):<br />
-COOH /^-CKO v |/\-COOH<br />
and y-nitroanthracene into anthraquinonoxime (Meisenheimer) :<br />
0<br />
H (j<br />
NOH<br />
This simple indigo synthesis <strong>of</strong> Baeyer should not be omitted if<br />
o-nitrobenzaldehyde is available.<br />
Experiment.—Dissolve 1 g. <strong>of</strong> o-nitrobenzaldehyde in 3 c.c. <strong>of</strong><br />
1 Ber., 1882, 15, 2856.
372 THIOINDIGO<br />
pure acetone, add about an equal volume <strong>of</strong> water, which leaves a<br />
clear solution, and then, drop by drop, iV-sodium hydroxide solution.<br />
Heat is developed and the solution becomes dark brown.<br />
After a short time the dye separates in crystalline flakes. Collect<br />
the precipitate at the pump after five minutes and wash, first with<br />
alcohol then with ether. Indigo so prepared is specially pure and<br />
has a beautiful violet lustre.<br />
The starting material for the first large-scale technical production <strong>of</strong><br />
indigo was naphthalene, which was oxidised with fuming sulphuric acid<br />
(in the presence <strong>of</strong> mercuric sulphate) to phthalic acid. The phthalimide<br />
obtained from this acid was partially hydrolysed, to the phthalamido<br />
acid, and then underwent the H<strong>of</strong>mann degradation to anthranUic acid.<br />
Combined with chloroacetic acid, the latter yielded phenylglycine-o-carboxylic<br />
acid, which on fusion with alkali furnishes indoxyl. (Formulate.)<br />
The synthesis <strong>of</strong> the red dye thioindigo (Friedlander), and its technically<br />
important derivatives, proceeds in a corresponding way. The<br />
starting material is thiosalicylic acid :<br />
y, XJOOH<br />
> | 1 CH2.COOH<br />
In the synthesis due to Heumann and Pfleger the fusion yields the<br />
potassium derivative <strong>of</strong> indoxyl, which is dehydrogenated to indigo<br />
even by atmospheric oxygen ; at the same time hydrogen peroxide is<br />
produced (see p. 175).<br />
Hardly any other organic compound has been so much examined<br />
from every point <strong>of</strong> view as indigo, and we must therefore confine ourselves<br />
here to a few <strong>of</strong> the most important reactions.<br />
The <strong>Chemistry</strong> <strong>of</strong> Indigo Dyeing.—On account <strong>of</strong> its insolubility the<br />
dye itself cannot be applied directly to the fibre. Yet an indirect process<br />
<strong>of</strong> great antiquity is available, for Tyrian purple has been identified<br />
as 6 : 6'-dibromoindigo 1 by Friedlander. The indigo is made soluble<br />
1 The two bromine atoms are in the m-poaitions to the nitrogen.
VAT DYEING 373<br />
by reduction in alkaline solution and so converted into the alkali<br />
salt <strong>of</strong> its dihydro compound ; in technical language, indigo is a vat<br />
dye. Primitive peoples have, from remote times, brought about this<br />
conversion biologically, i.e. by means <strong>of</strong> reducing bacteria. In industry<br />
ferrous hydroxide or zinc dust was used, now replaced by sodium hydrosulphite.<br />
Experiment.-—Grind about 50 mg. <strong>of</strong> the indigotin prepared, in a<br />
small mortar, with a few drops <strong>of</strong> water to a fine sludge, wash this<br />
into a small conical flask with a jet <strong>of</strong> water from a wash-bottle, and<br />
after adding a small excess <strong>of</strong> alkaline sodium hydrosulphite solution<br />
warm to 30°-40°. Soon a greenish-yellow, then brownish solution,<br />
the vat, is produced. At the surface <strong>of</strong> this solution there forms,<br />
as a result <strong>of</strong> contact with the air, a fine blue film, the so-called<br />
" bloom ". Dilute with water to 25-30 c.c, introduce a previously<br />
moistened strip <strong>of</strong> linen into the solution, and stir with a glass rod<br />
for about a minute. Then withdraw the cloth, press it, and hang it<br />
over two parallel stretched strings or over two thin glass rods.<br />
Already after five minutes the material is coloured deep blue.<br />
Precipitate the dye again from the vat by drawing air through<br />
the solution. This process is also suitable for purifying indigo.<br />
Chemically, conversion into a vat consists in a 1 : 6-addition <strong>of</strong><br />
hydrogen and recalls exactly the conversion <strong>of</strong> quinone into quinol.<br />
Like quinol, " indigo white ", also a dihydric " phenol ", is a weak acid,<br />
the alkali salts <strong>of</strong> which are coloured intensely yellow.<br />
iO<br />
NH<br />
sC=C*<br />
OH OH<br />
From its alkali salt, which is partially hydrolysed, the large " indigo<br />
white " molecule is adsorbed by the fibre and then, in this finely divided<br />
condition, dehydrogenated by the oxygen <strong>of</strong> the air, so that the dye now<br />
remains as a fast blue pigment. The oxidation is analogous to that <strong>of</strong><br />
indoxyl.<br />
The vat dyes are characterised by quite unusual fastness ; apart<br />
from the true indigoids, the most important members <strong>of</strong> this group<br />
are found in the anthraquinone series. (Indigoids are dyes containing<br />
ring systems <strong>of</strong> the type present in indigo connected by a double bond.)<br />
Almost without exception these dyes contain condensed rings possessing<br />
great chemical stability. The blue dye indanthrene, which is obtained
374 DBHYDKOINDIGO<br />
from the technically very important jS-aminoanthraquinone by fusion<br />
with alkali (with accompanying elimination <strong>of</strong> hydrogen), may be taken<br />
as an example <strong>of</strong> an anthraquinone vat dye (R. Bohn) :<br />
CO CO<br />
Although indigo on conversion into " indigo white" takes up<br />
hydrogen, and energetic reduction even breaks the double bond and.<br />
yields indoxyl and indole, it can also be dehydrogenated by a not less<br />
remarkable reaction. The hydrogen is removed from the NH-groups<br />
<strong>of</strong> the indole ring most readily by lead peroxide (Kalb):<br />
CO CO CO CO<br />
N<br />
The dehydroindigo which is thus formed is much more soluble than<br />
indigo itself. It is a beautifully crystalline brownish-red substance<br />
which is very easily hydrogenated, even by quinol, for example, in the<br />
manner shown in the above equation (read from right to left). The<br />
quinol, <strong>of</strong> course, is converted into quinone.<br />
Experiment. 1 -—Heat as much finely powdered indigo as amply<br />
covers the tip <strong>of</strong> a knife with about twice as much lead peroxide, a<br />
few granules <strong>of</strong> calcium chloride, and 5 c.c. <strong>of</strong> benzene in a test tube<br />
held in a boiling water bath for five minutes. Filter the reddishbrown<br />
solution obtained and divide the filtrate into two portions<br />
in test tubes. To one portion add quinol dissolved in very little<br />
alcohol, to the other dilute solution <strong>of</strong> stannous chloride in hydrochloric<br />
acid. The dehydroindigo is converted into the dye which<br />
separates in blue flocks.<br />
Conversely a suspension <strong>of</strong> finely divided indigo in chlor<strong>of</strong>orm<br />
can be converted into a beautiful reddish-brown solution <strong>of</strong> dehydroindigo<br />
by adding first a little calcium hydroxide and then bromine<br />
drop by drop.<br />
1 L. Kalb, Ber., 1909, 42, 3649.
ISATIN 375<br />
The beautiful preparation should be isolated by the former <strong>of</strong><br />
Kalb's two procedures. 1<br />
The best known oxidative transformation <strong>of</strong> indigo is that into isatin.<br />
This is a normal oxidation at a double bond :<br />
CO CO CO CO<br />
Isatin is the inner anhydride (lactam) <strong>of</strong> a y-amino-a-ketocarboxylic<br />
acid, isatinic acid (A), and is converted into a salt <strong>of</strong> this acid by the<br />
action <strong>of</strong> alkali. The keto-group in position 3 can condense with many<br />
other substances, and for this reason isatin is manufactured on a technical<br />
scale and converted into valuable indigoid vat dyes. The magnificent<br />
thioindigo scarlet, which is obtained from isatin and a sulphur<br />
analogue <strong>of</strong> indoxyl (the so-called hydroxythionaphthene), may be taken<br />
as example: QQ<br />
co co c=c/<br />
Sandmeyer's valuable isatin synthesis involves the removal <strong>of</strong><br />
sulphur from diphenylthiourea (I) (p. 169) with basic lead carbonate.<br />
Hydrogen cyanide is combined with the reactive diphenylcarbodiimide<br />
(II) so obtained, and the nitrile (III) produced is converted by means<br />
<strong>of</strong> hydrogen sulphide into the thioamide (IV). Concentrated sulphuric<br />
acid brings about ring closure and the product is the a-anil <strong>of</strong> isatin (V).<br />
Then, by hydrolysis with dilute sulphuric acid, aniline is removed :<br />
CN<br />
(C6H5NH)2.C8 —> C6H5.N=C=N.C6H5 >- [ IIIJ ^C=*<br />
C=NC6H5.<br />
Sandmeyer's synthesis may be recommended also as a preparative<br />
method.<br />
It may be recalled that the first synthesis <strong>of</strong> indigo, by Baeyer,<br />
started from isatin chloride. (Formulate it.)
CHAPTEK XI<br />
HYDEOGENATION AND EEDUCTION, OZONISATION<br />
1. CATALYTIC HYDROGENATION WITH PALLADIUM<br />
FIG. 57 shows the manner in which the apparatus is arranged. 1<br />
The confining liquid in the gas-holder is water. A Kabe turbine,<br />
a small electro-motor or a hot-air engine,<br />
which turns an eccentric attached by means<br />
<strong>of</strong> a rigid wire to the hydrogenation bulb,<br />
serves as a shaker. (If, however, the wire<br />
is in two parts, as the figure shows, the<br />
apparatus can be dismantled more con-<br />
veniently. The parts are connected by<br />
means <strong>of</strong> a brass sleeve provided with a<br />
screw.) All the stands are weighted with<br />
heavy pieces <strong>of</strong> iron. In the side <strong>of</strong> the bulb itself (Fig. 58) there<br />
is an opening which can be closed with a (clean) rubber stopper.<br />
The horizontal tube <strong>of</strong> the bulb, which is at the same time<br />
the axis about which the bulb oscillates, turns in a brass sleeve<br />
(cork borer) held in position by short pieces <strong>of</strong> rubber tubing<br />
drawn over the glass. A strong clamp grips a cork through which<br />
1 The stands for the gas-holder, hydrogenation vessel, and eccentuc are not<br />
shown in the figure.<br />
376
CATALYTIC HYDKOGBNATION 377<br />
the sleeve is pushed and thus maintains stability. By means <strong>of</strong><br />
a thick-walled rubber tube carrying a spring clip the glass tube<br />
is directly connected to the gas-holder.<br />
<strong>of</strong> the latter is fixed in a large<br />
condenser clamp.<br />
Before hydrogenation is begun<br />
The measuring cylinder<br />
the whole apparatus is tested for gas-tightness<br />
as follows: The opening at the side <strong>of</strong> the bulb<br />
is closed, and by turning the cocks A and<br />
B the gas-holder is provisionally filled with<br />
hydrogen. After closing the cocks the level<br />
<strong>of</strong> the water in the cylinder is marked<br />
while it is at the same height as that <strong>of</strong> the<br />
water in the container, and the empty bulb<br />
is shaken for a quarter <strong>of</strong> an hour. If the<br />
level is unchanged after this period (with<br />
unaltered room temperature)<br />
can proceed.<br />
hydrogenation<br />
FIG. 58<br />
0-5 g. <strong>of</strong> palladium on charcoal (see p. 378) is put into the dry<br />
bulb (which still is full <strong>of</strong> air) and a solution <strong>of</strong> 5 g. <strong>of</strong> cinnaniic<br />
acid in 30 c.c. <strong>of</strong> 80 per cent methyl alcohol is cautiously<br />
added. The catalyst must be completely covered by the solution—<br />
an explosion may occur when hydrogen is admitted if traces <strong>of</strong> the<br />
catalyst remain fixed to the walls <strong>of</strong> the bulb. The cock B is closed,<br />
A is opened, and hydrogen (washed with potassium permanganate<br />
solution) is passed in from a cylinder until all the air has been displaced<br />
from bulb and tubes. Previously the gas-holder (capacity<br />
1 litre) and the tubes to the cock B have been filled with water,<br />
which is now driven out by hydrogen after A has been closed, B<br />
opened, and the water container lowered. The side opening is<br />
now closed, the hydrogen cylinder (or Kipp) is disconnected, the<br />
level <strong>of</strong> the liquid read as when testing for gas-tightness, and the<br />
shaking apparatus is set in motion. 1 The container stands on the<br />
gas-holder so that a slight pressure is maintained.<br />
Although the amount <strong>of</strong> catalyst used here is very small (about<br />
15 mg. <strong>of</strong> Pd), sufficient hydrogen to saturate the ethylene double<br />
1 If it ia neceaaary to refill the gas-holder during the experiment owing to conaumption<br />
<strong>of</strong> gas, the cylinder ia connected to A, the clip on the connecting rubber<br />
tubing <strong>of</strong> the horizontal tube <strong>of</strong> the bulb ia acrewed down, the cocks A and B are<br />
opened, and hydrogen ia carefully passed in.
378 USB OF PALLADIUM<br />
bond is nevertheless taken up in three hours (at 20° and a barometric<br />
pressure <strong>of</strong> 740 mm., 840 c.c). The flocculated palladium is removed<br />
by filtration, the methyl alcohol is evaporated, and the hydrogenated<br />
acid is recrystallised as described on p. 234.<br />
If undiluted methyl alcohol is used as a solvent a secondary catalytic<br />
action <strong>of</strong> the palladium results in the production <strong>of</strong> ester. 1 In this case<br />
5 g. <strong>of</strong> potassium hydroxide are added, the solution is concentrated by<br />
heating, and hydrocinnamic acid precipitated with dilute hydrochloric<br />
acid.<br />
Calculation <strong>of</strong> the Amount <strong>of</strong> Hydrogen Required<br />
One mole <strong>of</strong> substance requires for each double bond 224 litres <strong>of</strong><br />
hydrogen under standard conditions. The volume <strong>of</strong> a mole <strong>of</strong> hydrogen<br />
under the experimental conditions which prevail can be calculated from<br />
the formula<br />
Y Y 760T<br />
~ °273&'<br />
where b is the observed barometric pressure less the vapour pressure <strong>of</strong><br />
water at the temperature concerned, and T is the absolute temperature.<br />
Generally (for b = 760 mm. and t = 15°) it amounts to 24 litres. Five<br />
grammes <strong>of</strong> cinnamic acid (mol. wt. 148) =5/148 mole ; the volume <strong>of</strong><br />
hydrogen required is therefore 24 x 5/148 litre =811 c.c.<br />
Preparation <strong>of</strong> Palladium on Charcoal<br />
Suspend 2 g. <strong>of</strong> animal charcoal in 100 c.c. <strong>of</strong> water in a hydrogenation<br />
bulb (capacity about 300 c.c). By means <strong>of</strong> a rubber stopper attach a<br />
dropping funnel with bent stem to the side opening <strong>of</strong> the bulb, open the<br />
cock on the funnel and pass hydrogen into the bulb until a sample <strong>of</strong> the<br />
escaping gas, collected in a test-tube, burns with a steady flame. Now<br />
close the cock on the dropping funnel, lower the levelling vessel and run<br />
in gradually from the funnel (with continuous mechanical shaking) a<br />
solution <strong>of</strong> 0-1 g. <strong>of</strong> palladium chloride in 10 c.c. <strong>of</strong> approximately 0-1 N<br />
hydrochloric acid. When the solution has lost its colour, open the bulb<br />
and let the hydrogen escape. Filter the mixture at the pump, collecting<br />
the catalyst on a filter plate, and wash with much water keeping the<br />
catalyst always covered since gentle ignition occurs on exposure to the<br />
air. When acid can no longer be detected in the filtrate, rapidly wash<br />
twice with alcohol and absolute ether, immediately transfer the material,<br />
still moist with ether, to a desiccator, and evacuate. After 24 hours<br />
cautiously admit nitrogen or carbon dioxide before opening. The<br />
completely dry catalyst does not glow in air and can readily be kept.<br />
1 Cf. E. Waser, Helv. Chim. Ada, 1925, 8, 117.
USB OF NICKEL 379<br />
Preparation <strong>of</strong> Platinum Oxide, PtO2 1<br />
Platinum oxide catalyst prepared by the method <strong>of</strong> R. Adams has<br />
recently come into use because it is very convenient to prepare and<br />
handle and at the same time has very high activity. When in use it is<br />
first reduced by hydrogen in the hydrogenation bulb to very finely<br />
divided platinum.<br />
Dissolve 2-1 g. <strong>of</strong> platinic chloride (H2PtCl6) in 5 c.c. <strong>of</strong> water<br />
in a large porcelain crucible, mix with 20 g. <strong>of</strong> pure sodium nitrate,<br />
and evaporate the water over a small flame, stirring continuously<br />
with a thick glass rod. Then gradually raise the temperature until<br />
the contents <strong>of</strong> the crucible are completely fused. Nitrogen peroxide<br />
is evolved. Meanwhile, by heating with two powerful Bunsen<br />
burners, raise the melt to moderate red heat (500-600°). Evolution<br />
<strong>of</strong> NO2 decreases greatly after five to ten minutes. Allow to cool,<br />
extract with distilled water, wash the heavy residue several times by<br />
decantation, filter at the pump, and dry in a desiccator. Platinum<br />
oxide so produced should have a moderately dark-brown colour.<br />
2. CATALYTIC HYDROGENATION WITH NICKEL.<br />
CYCLOHEXANOL *<br />
Half a porous plate is broken into pieces the size <strong>of</strong> small peas<br />
and the fragments, after being mixed with a solution <strong>of</strong> 40 g. <strong>of</strong><br />
chlorine-free nickel nitrate in 20 c.c. <strong>of</strong> water, are dried, with stirring,<br />
on the water bath. The impregnated material is then heated at dull<br />
redness in a nickel crucible until evolution <strong>of</strong> oxides <strong>of</strong> nitrogen<br />
ceases and filled into a combustion tube (leaving at each end 10 cm.<br />
empty).<br />
The tube is then heated in a slightly sloping bomb furnace, or,<br />
better, in an electric resistance furnace, 3 while a stream <strong>of</strong> hydrogen,<br />
which is washed with saturated permanganate solution and dried in<br />
two wash-bottles containing concentrated sulphuric acid, is passed<br />
through. An adapter is fitted to the other end <strong>of</strong> the tube and afterwards,<br />
when the nickel oxide has been reduced, is kept with its<br />
point dipping into a vessel containing concentrated sulphuric acid<br />
(to prevent the entrance <strong>of</strong> air).<br />
1 J. Amer. Chem. Soc., 1922, 44, 1397 ; 1923, 45, 2171.<br />
2 Sabatier, Gompt. rend., 1903, 173, 1025.<br />
8 Such furnaces can easily be constructed from simple materials. See, for<br />
example, H. Rupe, Helv. Chim. Acta, 1918, 1, 454; Chem. Fabr., 1929, 50, 519-<br />
Cf. also Handbuch der Physik, H. Geiger and K. Scheel, 11, 370 et seq.
380 CYCLOHEXANOL<br />
Before the tube is heated it must be completely filled with hydrogen<br />
; test a sample <strong>of</strong> the issuing gas by collection in a small test<br />
tube and ignition.<br />
The tube is now heated while a current <strong>of</strong> hydrogen passes, and<br />
the temperature is maintained at 300°-310° until water ceases to<br />
appear in the adapter ; one and half to two hours are required.<br />
Then the contents <strong>of</strong> the tube are allowed to cool in a slow stream <strong>of</strong><br />
hydrogen.<br />
Meanwhile 25 g. <strong>of</strong> freshly distilled phenol are poured into a small<br />
distilling flask, the side tube <strong>of</strong> which is attached low down on the<br />
neck. Through a cork in the neck a delivery tube reaches to the<br />
bottom <strong>of</strong> the bulb whilst the side tube is pushed through another<br />
cork into the combustion tube. The end <strong>of</strong> the side tube reaches the<br />
heated zone. In order to restrict the amount <strong>of</strong> air which enters the<br />
tube when the distilling flask is attached the previous inlet tube is<br />
quickly replaced by a cork (fitted in advance), hydrogen is then<br />
passed through the phenol, and then the side tube <strong>of</strong> the flask is<br />
quickly fixed in the combustion tube. After a test <strong>of</strong> the issuing<br />
gas has shown the absence <strong>of</strong> air, a rather slow stream <strong>of</strong> hydrogen is<br />
passed while the furnace is gradually heated to 185°-190° and the<br />
distilling flask is dipped as deeply as possible into an oil bath at 140 0 , 1<br />
and after the two temperatures have been reached a vigorous stream<br />
<strong>of</strong> hydrogen is passed through. The hydrogenation product is<br />
collected in a small filter flask kept cool in ice. To this flask a second<br />
receiver containing a little ether is attached, which is likewise kept<br />
cool and serves at the same time as a bubble-counter for gauging<br />
the consumption <strong>of</strong> hydrogen.<br />
After three hours, on the average, the phenol has been completely<br />
evaporated and driven over the catalyst. When the receivers have<br />
been disconnected the hydrogen current is slowed down and the tube<br />
allowed to cool. The contents <strong>of</strong> the receivers are washed with a<br />
little ether into a small dropping funnel and shaken with 10 c.c.<br />
<strong>of</strong> 50 per cent sodium hydroxide solution in order to remove<br />
non-hydrogenated phenol. The solution is then decanted from the<br />
sodium phenoxide, which is washed with ether and dried with a little<br />
1 Vapour pressure <strong>of</strong> phenol: t. 120° 131° 139° 145°<br />
mm. 100 150 200 250<br />
The stoicheiometrical ratio <strong>of</strong> 1 mole <strong>of</strong> phenol to 3 moles <strong>of</strong> hydrogen would<br />
normally require a phenol pressure <strong>of</strong> 760/4 = 190 nun., but in the present case<br />
complete saturation is not attained.
CYCLOHEXANE 381<br />
potassium carbonate after removal <strong>of</strong> small amounts <strong>of</strong> cyclohexanone<br />
by thorough shaking with 40 per cent bisulphite solution.<br />
When the ether has been evaporated in a bath at 50° the residue is<br />
fractionated. As the boiling point rises, a little cyclohexane at first<br />
passes over with the ether ; heating is then continued over a naked<br />
flame and pure cyclohexanol distils as a colourless liquid at 160°-161°.<br />
The yield is 18-20 g. (75 per cent <strong>of</strong> the theoretical). If the experiment<br />
is performed with care and precision this amount can easily be<br />
obtained.<br />
If the catalyst has shown itself to be active the experiment can be<br />
directly followed by the hydrogenation <strong>of</strong> (thiophene-free l ) benzene ;<br />
after the furnace has cooled the connections are changed as above<br />
described. In the same time and at the same temperature 40 g. <strong>of</strong><br />
benzene can be hydrogenated. The hydrocarbon is evaporated from<br />
a water bath at 26°-28° in the same way as in the case <strong>of</strong> phenol.<br />
Unchanged benzene is removed from the reaction product by<br />
thorough shaking with 10 per cent fuming sulphuric acid (cf. Chap.<br />
IV. 1, p. 191). Cyclohexane boils at 81° and, like benzene, solidifies<br />
in ice.<br />
During the last two decades catalytic hydrogenation has acquired<br />
extraordinarily great importance for all branches <strong>of</strong> organic chemical<br />
practice. Sabatier first showed (1901) that a great variety <strong>of</strong> unsaturated<br />
substances are hydrogenated by passing their vapours together<br />
with hydrogen over heated, finely divided nickel. The application <strong>of</strong><br />
the method to the hydrogenation <strong>of</strong> liquids is due to Normann, who<br />
showed that fatty oils are changed into fats <strong>of</strong> higher melting point by<br />
addition <strong>of</strong> hydrogen with the aid <strong>of</strong> a nickel catalyst suspended in<br />
them. (Technical process for hardening fats.) According to the same<br />
principle the hydrogenation products <strong>of</strong> naphthalene (tetraUn and decalin)<br />
are prepared on an industrial scale (Schroter). When the degree <strong>of</strong><br />
subdivision <strong>of</strong> the nickel is increased by deposition on a carrier (kieselguhr,<br />
asbestos, barium sulphate) the activity is so increased that the<br />
hydrogen can be added to unsaturated substances even at room temperature<br />
and in solution (Kelber). 2 H. Rupe 3 has described the preparation<br />
<strong>of</strong> a particularly active nickel catalyst.<br />
The hydrogenation <strong>of</strong> the carbon-carbon double bond as a preparative<br />
task in the laboratory is usually carried out with the finely divided<br />
1 Pure commercial benzene is shaken in a machine for six to eight hours with onetenth<br />
<strong>of</strong> its volume <strong>of</strong> concentrated sulphuric acid ; the liquids are separated with<br />
a funnel and the benzene, after being shaken with sodium hydroxide solution, is<br />
distilled. Test with isatin and sulphuric acid.<br />
2 Ber., 1916, 49, 55 ; 1924, 57, 136.<br />
3 Helv. GUm. Ada, 1918, 1, 453.
382 CATALYTIC HYDKOGENATION<br />
platinum metals, platinum or palladium, in the form <strong>of</strong> platinum<br />
sponge, palladium black, platinum oxide or the metals precipitated in<br />
finely divided form on chemically indifferent carriers.<br />
Before metallic catalysts were used as carriers there was no possibility<br />
<strong>of</strong> adding elementary hydrogen directly to the carbon-carbon<br />
double bond. In such catalysts we have agents by means <strong>of</strong> which<br />
it is possible to saturate with hydrogen practically all unsaturated<br />
systems, and it is indeed the olefinic double bond which is most readily<br />
attacked by catalytically activated hydrogen. Such hydrogen does not<br />
react so quickly with the carbonyl group <strong>of</strong> aldehydes and ketones,<br />
whilst it leaves carboxyl and ester groups intact.<br />
The solvents which, in the scientific laboratory, have by far the<br />
greatest importance for catalytic hydrogenation in the cold are glacial<br />
acetic acid, ethyl acetate, the alcohols, ether, and water. The success<br />
<strong>of</strong> a hydrogenation depends, in a manner not yet quite clear, on the nature<br />
<strong>of</strong> the solvent. In general the most powerful effect is obtained with<br />
platinum oxide in glacial acetic acid. Since the solubility <strong>of</strong> hydrogen'<br />
in all solvents is low, the catalyst, in suspension or colloidal solution,<br />
must be continuously kept in contact with the gas phase by shaking, so<br />
that it can always take up further amounts <strong>of</strong> hydrogen and give them<br />
up again to the substance undergoing hydrogenation. Instead <strong>of</strong> the<br />
bulb-shaped hydrogenation vessel described above (Willstatter and<br />
Waser), a " shaking duck " may be used with equally good results.<br />
Frequently a hydrogenation, after proceeding well at the start, comes to<br />
a stop before the uptake <strong>of</strong> hydrogen is complete; in many cases the<br />
catalysts can then be reactivated by shaking with air (Willstatter). In<br />
this connexion it must be borne in mind that a mixture <strong>of</strong> hydrogen<br />
and air is ignited by the finely divided metallic catalyst, and that, therefore,<br />
before reactivation is undertaken, the hydrogen present in the<br />
hydrogenation vessel must be replaced by nitrogen or, more simply,<br />
removed by evacuation.<br />
Only completely pure substances should be subjected to catalytic<br />
hydrogenation. This rule is based on the fact that the catalyst is<br />
inactivated especially by substances containing sulphur and <strong>of</strong>ten also<br />
by those containing halogen ; not infrequently incalculable influences<br />
interfere with hydrogenation. The most certain means <strong>of</strong> avoiding<br />
such troubles is to use pure materials and also pure solvents.<br />
The same catalysts which permit the addition <strong>of</strong> elementary hydrogen<br />
to a double bond are able to accelerate the opposite process—dehydrogenation,<br />
or elimination <strong>of</strong> hydrogen—when the temperature is<br />
altered. Thus cyclohexane is decomposed into benzene and hydrogen<br />
when passed over nickel or palladium black at about 300° (Sabatier,<br />
Zelinsky). The equilibrium<br />
lies on the right side <strong>of</strong> the equation at the lower temperature, but at
CLEMMBNSEN'S METHOD 383<br />
the higher temperature the energy-consuming process, dehydrogenation,<br />
takes precedence. Without the catalyst both reactions proceed<br />
unmeasurably slowly; they are accelerated in identical fashion by<br />
its presence.<br />
On dehydrogenation with selenium see p. 416.<br />
3. REPLACEMENT OF THE OXYGEN IN CARBONYL<br />
COMPOUNDS BY HYDROGEN<br />
(Reduction by Clemmensen's Method)<br />
Ketones and aldehydes can be deoxidised, usually very readily,<br />
with amalgamated zinc and hydrochloric acid ; from the groups<br />
>C=O and —CH=O there are formed >CH2 and —CH3.<br />
Preparation <strong>of</strong> the Zinc Amalgam.—Granulated zinc in thin pieces<br />
or, still better, zinc foil 0-15 to 0-25 mm. thick and cut into small<br />
strips, is left for one hour with frequent shaking in contact with an<br />
equal weight <strong>of</strong> 5 per cent aqueous mercuric chloride solution. The<br />
solution is then poured <strong>of</strong>f and the metal washed once with fresh<br />
water.<br />
(a) Ethylbenzene from Acetophenone. 1 —Acetophenone (6 g.) and<br />
hydrochloric acid (30 c.c. from 1 part <strong>of</strong> concentrated acid and<br />
2 parts <strong>of</strong> water) are heated with 15 g. <strong>of</strong> amalgamated zinc to<br />
vigorous boiling on wire gauze in a flask attached to a reflux condenser<br />
by means <strong>of</strong> a ground joint. Boiling is continued for five<br />
hours and at the end <strong>of</strong> each hour 5 c.c. <strong>of</strong> concentrated hydrochloric<br />
acid are added. Then the hydrocarb6n produced is distilled in a<br />
few minutes with steam, separated from water by means <strong>of</strong> a small<br />
dropping funnel, dried with calcium chloride, and distilled. Boiling<br />
point 135°-136°. Yield 3-4 g. The yield can be increased if the<br />
acetophenone is added slowly drop by drop.<br />
(6) Dibenzyl from Benzil. 2 —Benzil (7 g.) and hydrochloric acid<br />
(1 :1, 100 c.c.) are boiled for five hours under reflux with 30 g. <strong>of</strong><br />
amalgamated zinc. Concentrated hydrochloric acid (20 c.c. in all)<br />
is poured in from time to time as described under (a). When the<br />
reaction is over the liquid is decanted from the zinc and cooled. The<br />
reaction product solidifies and is collected by filtration and washed<br />
several times with water. It is then distilled in a small sausage<br />
flask. Boiling point 280°. Melting point 50°-52°. The hydro-<br />
1 E. Clemmensen, Ber., 1913, 46, 1838.<br />
2 Ber., 1914, 47, 683.
384 ADIPIC ALDEHYDE FROM CYCLOHEXENE<br />
carbon can be recrystallised from a little alcohol. Yield 5 g.<br />
(almost theoretical).<br />
Benzoin can be reduced to dibenzyl in the same way.<br />
For the replacement <strong>of</strong> oxygen by hydrogen in ketones and aldehydes<br />
the method <strong>of</strong> Kishner and Wolff is used as <strong>of</strong>ten as is that <strong>of</strong> Clemmensen.<br />
In the former method the hydrazone or semicarbazone <strong>of</strong> the carbonyl<br />
compound is heated for several hours—preferably in the presence <strong>of</strong><br />
hydrazine hydrate—in a sealed tube or autoclave with sodium ethoxide<br />
at about 160°. The explanation <strong>of</strong> the reaction is that, under<br />
the catalytic influence <strong>of</strong> the ethoxide, the hydrazone is transformed<br />
into a diimine which then decomposes in the same way as does<br />
phenyldiimine (p. 286):<br />
T> T> T><br />
\ = N — N H 2 >- \ C H — N = N H ><br />
The reverse process, conversion <strong>of</strong> >CH2 into >CO succeeds in the<br />
case <strong>of</strong> ketones with selenium dioxide. Thus acetone may be directly<br />
oxidised to meihylglyoxal. This oxidising agent has been used very<br />
frequently recently because <strong>of</strong> the great variety <strong>of</strong> ways in which it can<br />
be applied.<br />
4. ADIPIC ALDEHYDE FROM CYCLOHEXENE BY OZONISATION 1<br />
Carry out the ozonisation in a thin-walled gas wash-bottle<br />
(capacity 400 c.c.) with an inlet tube widened out to a bell shaped<br />
opening or twisted to a spiral. Connect the bottle to the ozoniser<br />
by bending the inlet tube <strong>of</strong> the former at a right angle so that<br />
it can be inserted into the delivery tube <strong>of</strong> the ozoniser, which is<br />
fitted with a mercury seal.<br />
Dissolve 16 g. <strong>of</strong> cyclohexene in 200 c.c. <strong>of</strong> pure, dry ethyl<br />
acetate, 2 cool the solution in the bottle with an efficient ice-salt<br />
mixture to - 20° (or, better, with solid carbon dioxide in acetone to<br />
- 50° to - 70°) and then connect to the ozoniser.<br />
During the ozonisation keep the freezing mixture in an insulated<br />
jar (see p. 2) in order to maintain the best possible cooling efEect.<br />
If an ozoniser with at least five discharge tubes is used a very vigorous<br />
current <strong>of</strong> ozonised oxygen can be employed and the operation completed<br />
in from four to seven hours. For example, if twenty litres<br />
1 F. G. Fischer and K. Loewenberg, Ber., 1933, 66, 666.<br />
2 Shake ethyl acetate four times with an equal volume <strong>of</strong> water, dry over<br />
calcium chloride, and distil.
ADIPIC ALDEHYDE FROM CYCLOHEXENE 385<br />
per hour are passed through and the ozone content is 5 per cent by<br />
volume the cyclohexene (0-2 mole) is saturated in five hours.<br />
The student is strongly recommended to determine iodometrically<br />
the amount <strong>of</strong> ozone delivered in a fixed time and to regulate the strength<br />
<strong>of</strong> the current <strong>of</strong> oxygen with a gas meter. The determination should be<br />
made before the experiment is begun about ten minutes after the current<br />
in the ozoniser has been switched on.<br />
Since over-ozonisation must be in any case avoided, attach a<br />
second wash bottle containing acid potassium iodide solution to the<br />
outlet tube <strong>of</strong> the first before the calculated time has elapsed. If no<br />
ground glass joint 1 is available, use a long bored cork stopper which<br />
has been dipped in molten paraffin wax.<br />
The end <strong>of</strong> the ozonisation is recognised by sudden extensive<br />
separation <strong>of</strong> iodine.<br />
Hydrogenate the clear mobile solution <strong>of</strong> the ozonide (still cold)<br />
by means <strong>of</strong> 0-5 g. <strong>of</strong> palladium on a carrier (see p. 378). Moderate<br />
the rapid uptake <strong>of</strong> hydrogen immediately after hydrogenation is<br />
begun by cooling the bulb in ice water. Finally allow the action to<br />
run to completion whilst the spontaneous evolution <strong>of</strong> heat continues.<br />
After about one hour and uptake <strong>of</strong> three quarters <strong>of</strong> the calculated<br />
amount <strong>of</strong> hydrogen the hydrogenation ceases. Less hydrogen is<br />
consumed if the cooling during ozonisation has been insufficient or if<br />
over-ozonisation has occurred.<br />
Remove the catalyst by filtration at the pump, distil the solvent<br />
using a receiver for fractional distillation and collect the adipic aldehyde<br />
by distillation in a vacuum from a small flask fitted with a<br />
column. Yield 12-14 g. Pure adipic aldehyde boils at 92°-94°/12<br />
mm., solidifies in an ice-salt freezing mixture and then melts at - 8°<br />
to - 7°. Keep it in a sealed tube under nitrogen or CO2 in order to<br />
protect it from auto-oxidation.<br />
When dealing with ozonides always wear goggles, since ozonides,<br />
in particular amongst compounds <strong>of</strong> low molecular weight, are <strong>of</strong>ten<br />
explosive. Benzene triozonide, for example, is very dangerous.<br />
Suitable solvents for the ozonisation <strong>of</strong> organic substances are :<br />
hexane, chlor<strong>of</strong>orm, carbon tetrachloride, ethyl chloride, glacial<br />
acetic acid, and ethyl acetate.<br />
Many ozonides are difficultly soluble in the hydrocarbons and<br />
chloro-compounds and consequently separate during the ozonisation.<br />
1 For rendering joints gas-tight when working with ozone use not fat but syrupy<br />
phosphorus pentoxide or graphite.<br />
20
CHAPTBK XI<br />
NATUEAL PRODUCTS<br />
1. FURFURAL 1<br />
BRAN<br />
c.c. <strong>of</strong><br />
(300<br />
concentrated<br />
g.) is stirred<br />
sulphuric<br />
in a<br />
acid<br />
three-litre<br />
and 800<br />
flask<br />
c.c.<br />
with<br />
<strong>of</strong><br />
a<br />
water.<br />
mixture<br />
Abo<br />
<strong>of</strong><br />
tion<br />
900<br />
with<br />
c.c. <strong>of</strong><br />
sodium<br />
the liquid<br />
carbonate,<br />
are distiled<br />
is saturated<br />
and the<br />
with<br />
distilate,<br />
common<br />
after<br />
salt<br />
neutralis<br />
Of this solution 300 c.c. are again distiled and the distilate<br />
(250<br />
is<br />
g<br />
and<br />
tracted<br />
the<br />
with<br />
ether<br />
ether<br />
evaporated.<br />
after saturation<br />
Then the<br />
with<br />
furfural<br />
salt. The<br />
is distiled.<br />
extract is<br />
Boiling<br />
dried<br />
point 162°. Yield 5-7 g.<br />
<strong>of</strong><br />
The<br />
water<br />
pentoses,<br />
and are converted<br />
when<br />
into<br />
boiled<br />
furfural.<br />
with mineral acids, lose thre<br />
CHOH—CHOH HC- CH HC—CH<br />
I I —•> I I —• I I<br />
H0CH2 CHOH.CHO HC C.CHO HC C.CHO.<br />
V Y<br />
The two most important natural pentoses, 1-arabinose and \-xylose,<br />
occur in nature as polymeric anhydrides, the so-called pentosans, viz.<br />
araban, the chief constituent <strong>of</strong> many vegetable gums (cherry gum,<br />
gum arable, bran gum), and xylan, in wood. From these pentapolyoses<br />
there are produced by hydrolysis first the simple pentoses which are<br />
then converted by sufficiently strong acids into furfural. This aldehyde<br />
is thus also produced as a by-product in the saccharification <strong>of</strong><br />
wood (cellulose) by dilute acids. Furfural, being a " tertiary " aldehyde,<br />
is very similar to benzaldehyde, and like the latter undergoes the<br />
acyloin reaction (furoin) and takes part in the Perkin synthesis. It<br />
also resembles benzaldehyde in its reaction with ammonia (p. 215).<br />
Experiments.-—Allow furfural to stand for a short time with five<br />
parts <strong>of</strong> aqueous ammonia ; after three hours, separation <strong>of</strong> the<br />
1 Stenhouse, Annalen, 1841, 35, 302 ; Fownes, Annalen, 1845, 54, 52.<br />
386
FURFURAL 387<br />
product is complete. Recrystallise from alcohol. Melting point<br />
117°. The substance has a structure analogous to that <strong>of</strong> hydrobenzamide.<br />
Furfural even in dilute aqueous solution gives, almost at once, a<br />
precipitate <strong>of</strong> the phenylhydrazone with phenylhydrazme acetate.<br />
Collect the precipitate at the pump and dry. Punfy by dissolution<br />
in a little ether and careful addition <strong>of</strong> petrol ether until crystallisation<br />
begins. Melting point 97°-98°. Method for quantitative determination<br />
<strong>of</strong> furfural.<br />
Furfural gives two characteristic colour reactions which serve foi<br />
qualitative detection. With phloroglucinol and hydrochloric acid<br />
(1 part concentrated acid, 1 part water) a cherry-red colour is produced<br />
on boiling , with a solution <strong>of</strong> aniline acetate a red colour is produced<br />
even in the cold.<br />
Carry out these two tests.<br />
The reaction with aniline salts was explained simultaneously by<br />
Zincke and by Dieckmann in 1905. The furane ring undergoes " aminolytic<br />
" cleavage and then the anil is formed from the aldehyde.<br />
CH—CH CH CH CH:C CHN C6H5<br />
II II I 1<br />
CH C—CHO + H2N.CeH5 C6H5.<br />
6 DO DO 5.NH HO<br />
H O<br />
C 6 H 5 N H<br />
T h e d y e s a r e s a l t s <strong>of</strong> t h e d i a n i l <strong>of</strong> a - h y d r o x y g l u t a c o n i c d i a l d e h y d e<br />
h a v i n g t h e a b o v e f o r m u l a ; i n s t e a d <strong>of</strong> C 6 H 5 . N H . C H = C H it is e q u a l l y<br />
g o o d t o w r i t e C 6 H 5 . N = C H — C H 2 — ; t h e r e l a t i o n s h i p s t o g l u t a c o n t c a c i d<br />
H O O C . C H 2 . C H - C H C O O H a n d t o its a l d e h y d e t h e n b e c o m e c l e a r e r .<br />
T h e c o l o u r e d s a l t s l o s e o n e m o l e c u l e o f a n i l i n e w h e n h e a t e d a n d a r e<br />
c o n v e r t e d i n t o q u a t e r n a r y f i - h y d r o x y p y n d i n i u m salts :<br />
C H C H<br />
HC C! O H H C C — O H<br />
C 6 H 5 . H N — H C C H<br />
H—N Y<br />
388 d-GLUCOSE. INVBKTASB<br />
hydrochloric acid and add alcohol till the volume is 10 c.c. Then<br />
add a solution <strong>of</strong> 1 c.c. <strong>of</strong> furfural in 8 c.c. <strong>of</strong> alcohol and warm for<br />
a short time. On cooling, the violet dye separates in fine needles.<br />
Collect the crystals at the pump and wash with a little alcohol and<br />
ether.<br />
2. d-GLUCOSE FROM CANE SUGAR 1<br />
A mixture <strong>of</strong> 750 c.c. <strong>of</strong> methylated spirit with 30 c.c. <strong>of</strong> fuming<br />
hydrochloric acid (d. 1-19) is heated to 45°-50° and at this temperature<br />
250 g. <strong>of</strong> pure, finely powdered cane sugar (castor sugar) are<br />
added in portions with continuous shaking. The sugar must dissolve<br />
completely. On cooling, the d-glucose produced is precipitated as<br />
a viscous resin while the d-fructose remains in solution. The resinous<br />
material is inoculated with a few decigrammes <strong>of</strong> anhydrous glucose.<br />
Crystallisation is promoted by frequent stirring with a glass rod,<br />
but nevertheless requires several days to reach completion. The<br />
precipitate is now an almost colourless fine crystalline powder which<br />
is collected at the pump and at once redissolved in 20-25 c.c. <strong>of</strong> hot<br />
water. Alcohol (120-150 c.c.) is then added to the hot solution until<br />
turbidity appears, and the liquid is allowed to cool with stirring and<br />
inoculation. The cold mixture is left over night and then filtered<br />
at the pump. The precipitate is washed with alcohol and well dried<br />
in a vacuum desiccator. Yield 50-60 g. Melting point 146°.<br />
3. HYDROLYSIS OF CANE SUGAR BY SACCHARASE (INVERTASE)<br />
(a) Preparation <strong>of</strong> the Enzyme Solution.* 1 —Pressed yeast (50 g.)<br />
is stirred in a small filter jar by means <strong>of</strong> a stout glass rod with 5 c.c.<br />
<strong>of</strong> toluene at 30° until the mixture forms a quite thin sludge (about<br />
three-quarters <strong>of</strong> an hour). This sludge, which results from the<br />
autolysis <strong>of</strong> the yeast cells, is diluted with 50 c.c. <strong>of</strong> water at 30°,<br />
and kept at this temperature for one hour. It is then diluted<br />
to 150 c.c. with water, in a conical flask (capacity 250 c.c),<br />
vigorously shaken with some kieselguhr, and poured rapidly on to a<br />
moderate-sized Biichner funnel to which slight suction is applied.<br />
The residue on the filter is again washed with 50 c.c. <strong>of</strong> water at 30°.<br />
The filtrate is thrown away ; it indeed contains a little invertase,<br />
but is chiefly a solution <strong>of</strong> other yeast constituents, which should<br />
thus be removed. The residue on the funnel is well beaten up with<br />
1 Soxhlet, J. pr. Chem., 1880, 21, 245.<br />
2 Willstatter, Schneider, and Bamann, Z. physiol. Chem., 1925, 147, 264.
HYDKOLYSIS OF CANE SUGAK 389<br />
50 c.c. <strong>of</strong> water, a few drops <strong>of</strong> toluene are added, and the mixture is<br />
left for fifteen hours at about 30° to allow the enzyme to be set free.<br />
In order now to remove proteins from the thin sludge it is vigorously<br />
stirred with 0-05 i\f-acetic acid in amount just sufficient to<br />
change the colour <strong>of</strong> methyl red (p^ = 4:) (test with a sample), and<br />
is then filtered as above after shaking with a little kieselguhr if<br />
necessary. The filtrate is made neutral to litmus with dilute<br />
ammonia and in this condition, protected by a little toluene, can be<br />
kept unchanged for several days.<br />
(6) The Inversion.-—Cane sugar (40 g.) is dissolved in 200 c.c. <strong>of</strong><br />
water in a 250 c.c. measuring flask, 25 c.c. <strong>of</strong> 10 per cent sodium<br />
dihydrogen phosphate solution are added and the mixture is warmed<br />
on a large water bath (or in a thermostat) at 30°. Now 10 c.c. <strong>of</strong><br />
the enzyme solution prepared as described under (a) are added and<br />
the time at which the latter has run out <strong>of</strong> the pipette is noted. The<br />
flask is filled at once to the mark with water at 30° and shaken up.<br />
The first 25 c.c. sample is removed for polarisation and the time is<br />
noted in the same way as was done just before. Bach sample is<br />
run into 5 c.c. <strong>of</strong> 2iV^-sodium carbonate solution in order to stop<br />
the action <strong>of</strong> the enzyme and at the same time to accelerate the<br />
" mutarotation " (p. 395). After shaking it with a little animal<br />
charcoal the sample is poured through a dry filter and the clear<br />
solution is polarised in a 2-dm. tube. Each time the average <strong>of</strong><br />
three readings is taken.<br />
The main solution in which the reaction goes on is kept at 30°.<br />
From it samples are taken for polarisation every twenty minutes<br />
during the first hour after the beginning <strong>of</strong> the experiment, and every<br />
thirty minutes during the second hour. During this reaction period<br />
that stage <strong>of</strong> the inversion which is shown by zero rotation is usually<br />
passed. This indicates that about 75 per cent <strong>of</strong> the cane sugar<br />
taken has been hydrolysed.<br />
When the rotations are plotted as ordinates against the times<br />
as abscissae, the observed points can be connected by a logarithmic<br />
curve, which is flatter in the later stages <strong>of</strong> the reaction and indicates<br />
the order as unimolecular. The abscissa <strong>of</strong> the point in this curve corresponding<br />
to a rotation <strong>of</strong> 0° gives the " zero-rotation time ", which<br />
is to some extent a measure <strong>of</strong> the activity <strong>of</strong> the enzyme solution<br />
employed.<br />
The course <strong>of</strong> the curve already indicates that the logarithmic law<br />
is not strictly obeyed. By exterpolation we can obtain the point <strong>of</strong>
390 a-ACBTOBKOMOGLUCOSB •<br />
intersection <strong>of</strong> the curve with the Y-axis, and so the rotation at zero<br />
time; if one-third <strong>of</strong> this initial dextro-rotation is plotted (as final laevorotation)<br />
below the rotation <strong>of</strong> 0° on the Y-axis, the time when this<br />
ultimate rotation is approximately reached can be ascertained graphically.<br />
We next test whether the half-value time is constant, i.e. whether<br />
the moments at which one-half, one-quarter, one-eighth <strong>of</strong> the total<br />
change in rotation have still to occur and similar fractions <strong>of</strong> the sugar<br />
remain unhydrolysed (as indicated by the curve) are really separated<br />
by equal intervals <strong>of</strong> time. Since the diminution in the rotation is<br />
directly proportional to the amount <strong>of</strong> sugar inverted, this diminution<br />
is at once a measure <strong>of</strong> the reaction velocity.<br />
The observed changes <strong>of</strong> rotation and the corresponding times<br />
should be substituted in the following equation for unimolecular reactions,<br />
and the constant K should be calculated.<br />
log (at - a) - log (a2 - a)<br />
0-4343(
LACTOSE AND CASEIN FKOM MILK 391<br />
<strong>of</strong> the finely powdered peracetylated glucose, which is kept in ice.<br />
Dissolution is brought about by vigorous shaking, and the solution is<br />
left at room temperature for two hours. Then 850 c.c. <strong>of</strong> ice-water are<br />
added with stirring, the liquid is decanted from the precipitate which<br />
separates, and the latter, after thorough grinding in a basin with icewater,<br />
is collected at the pump and washed well. The crude product<br />
is dissolved in 250 c.c. <strong>of</strong> cold methyl alcohol, the solution is kept<br />
cool in ice, and an equal volume <strong>of</strong> cold water is slowly added. In<br />
this way the substance is precipitated in the pure crystalline state.<br />
It is collected at the pump, washed with water, and dried, first on<br />
porous plate and then very thoroughly in a vacuum desiccator over<br />
solid potassium hydroxide and concentrated sulphuric acid. Yield<br />
15-20 g.<br />
5. LACTOSE AND CASEIN FROM MILK<br />
Whole milk (2 litres) is diluted with an equal volume <strong>of</strong> water at<br />
30°-40° and commercial rennet (0-1 g.), dissolved in a few cubic<br />
centimetres <strong>of</strong> water, is added. The mixture is then left at the same<br />
temperature until separation <strong>of</strong> the casein is complete (about two<br />
hours). The whey is filtered through a filter cloth, and after the<br />
liquid has run <strong>of</strong>f the residue is pressed down well. The casein,<br />
which contains a great deal <strong>of</strong> fat, is ground in a mortar with a little<br />
1 per cent sodium hydroxide solution; 1 to 1 -5 litres <strong>of</strong> sodium<br />
hydroxide solution <strong>of</strong> the same concentration are then poured on to<br />
the resulting paste, and the mixture is gently warmed in a porcelain<br />
basin until all but the fat dissolves.<br />
When the mixture stands over night in a filter jar the milk fat<br />
collects at the surface and can be separated cleanly at the pump.<br />
The filtrate is combined with the rest <strong>of</strong> the casein solution and the<br />
substance is again precipitated by the addition <strong>of</strong> 10-20 c.c. <strong>of</strong><br />
glacial acetic acid. Finally the precipitate is collected by filtration<br />
loose glass beads covered with moist red phosphorus and a second U -tube containing<br />
calcium chloride, or preferably phosphorus pentoxide, is attached to the first.<br />
Bromine (20 c.c. =60 g.) is then slowly added to the phosphorus drop by drop from<br />
a funnel, the tube <strong>of</strong> which reaches nearly to the surface <strong>of</strong> the phosphorus. The<br />
reaction is very vigorous. The gas which is produced must be quite colourless when<br />
it has passed through the U-tube containing phosphorus. The most suitable receiver<br />
is a filter flask containing 40 c.c. <strong>of</strong> liquid glacial acetic acid, protected from<br />
atmospheric moisture by means <strong>of</strong> a calcium chloride tube. The receiver is kept<br />
cool in ice-water after part <strong>of</strong> the hydrogen bromide has been absorbed.<br />
A very convenient and cheap method (using industrial tetralin and bromine) is<br />
given in J. Houben, Methoden der organischen Chemie, 3rd edition, vol. iii. p. 1156.<br />
It is desirable to wash the gas with paraffin oil.
392 HYDKOLYSIS OF CASEIN<br />
through linen, washed well with water, and dried in a desiccator.<br />
Yield 50-60 g. (For the hydrolysis it is not necessary to dry the<br />
casein.)<br />
Lactose.-—The whey is concentrated to a small volume on a<br />
ring burner which causes almost complete precipitation <strong>of</strong> the<br />
albumin. The mixture is filtered through linen, and the filtrate<br />
is again concentrated until lactose separates. When the mixture<br />
is cold the crude crystalline sugar is collected by filtration through<br />
linen on a Biichner funnel and dried. A second portion <strong>of</strong> lactose is<br />
obtained by further concentration <strong>of</strong> the mother liquor-—this time<br />
on the water bath. Yield <strong>of</strong> crude material 70-75 g.<br />
The crude product is dissolved in the minimum amount <strong>of</strong> hot<br />
water (30-40 c.c.) and sufficient alcohol to produce a turbidity<br />
(about 100 c.c.) is added to the hot solution.<br />
In the course <strong>of</strong> a few hours copious crystallisation occurs. Precipitation<br />
<strong>of</strong> the crystals can be initiated and accelerated by scratching<br />
with a glass rod. The mixture is left over night before filtration,<br />
then the preparation is collected at the pump and washed with<br />
alcohol. Yield 60-65 g.<br />
Acid Hydrolysis <strong>of</strong> Casein. 1 —The casein is boiled for sixteen hours<br />
with three times its weight <strong>of</strong> 25 per cent sulphuric acid in a flask<br />
attached by means <strong>of</strong> a ground joint to a reflux condenser. The<br />
sulphuric acid is then removed from the dark-coloured liquid by<br />
means <strong>of</strong> hot saturated barium hydroxide solution and the slight<br />
excess <strong>of</strong> barium ions is precipitated with carbon dioxide. The<br />
precipitated material is boiled with 500 c.c. <strong>of</strong> water. A sample <strong>of</strong><br />
the barium sulphate precipitate again boiled with water should not<br />
react with Millon's reagent (see below). The filtrates are combined<br />
and concentrated until crystals begin to separate. After the crystals<br />
have been removed from the cold solution by filtration the mother<br />
liquor is again concentrated until crystallisation sets in once more,<br />
and this process is repeated two or three times until the filtrate gives<br />
but a feeble reaction for tyrosine.<br />
The various crops <strong>of</strong> crystals are combined and repeatedly recrystallised<br />
from hot water with addition <strong>of</strong> animal charcoal. A<br />
small amount <strong>of</strong> l-tyrosine is obtained in this way. Melting point<br />
<strong>of</strong> the pure compound 314°-318°.<br />
In addition some leudne and glutamic acid are obtained ; their<br />
purification is described in the handbook cited.<br />
1 Abderhalden, Handbuch der biolog. Arbeitsmethoden, I, 7, p. 19.
d-GALACTOSE FKOM LACTOSE 393<br />
Millon's reagent: Dissolve one part <strong>of</strong> mercury in two parts <strong>of</strong><br />
nitric acid (d. 1-42) first in the cold and then by warming. Dilute the<br />
solution with two volumes <strong>of</strong> water.<br />
6. d-GALACTOSE FROM LACTOSE. 1 MUCIC ACID. PYRROLE<br />
Lactose (100 g.) is boiled under reflux for two hours with 250 c.c.<br />
<strong>of</strong> water containing 3 c.c. <strong>of</strong> concentrated sulphuric acid, and finally<br />
for a few minutes with animal charcoal. The sulphuric acid is<br />
precipitated from the unfiltered liquid by addition to the well-shaken<br />
sugar solution <strong>of</strong> a hot saturated aqueous solution <strong>of</strong> the calculated<br />
amount <strong>of</strong> barium hydroxide (about 15 g. <strong>of</strong> Ba(0H)2, 8H2O). The<br />
liquid may not become alkaline. When the solution is free from<br />
sulphuric acid (and barium) the precipitated material is removed by<br />
nitration at the pump, and after adding 3 c.c. <strong>of</strong> glacial acetic acid<br />
the filtrate is concentrated in a vacuum to 60 c.c. on a bath at<br />
40°-50°. Glacial acetic acid (100 c.c.) is mixed with the syrup thus<br />
obtained, while it is still warm, until a clear solution is obtained.<br />
When this solution is cold and is scratched with a glass rod or seeded<br />
with a few crystals <strong>of</strong> galactose, the sugar crystallises. Crystals are<br />
allowed to separate for one day and are then collected at the pump,<br />
washed, first with a little cold glacial acetic acid, then with a little<br />
cold methyl alcohol, and finally with ether. Yield 20-25 g. Melting<br />
point 165°.<br />
Test the purity <strong>of</strong> the galactose prepared by determining the<br />
specific rotation with a polarimeter. An aqueous solution containing<br />
one gramme <strong>of</strong> substance in 10 c.c. should have a rotation <strong>of</strong> +8-15°<br />
in a decimetre tube. Hence [a]|°°= +81-5°.<br />
Since galactose exhibits mutarotation the attainment <strong>of</strong> equilibrium<br />
is accelarated by addition <strong>of</strong> a few drops <strong>of</strong> ammonia solution.<br />
Mucic Acid. 2 -—Galactose (25 g.) is mixed with nitric acid (300 c.c.;<br />
d. 1-15) and the mixture is concentrated to about 50 c.c. on the<br />
water bath with stirring.<br />
The pasty mass obtained on cooling is stirred with 50 c.c. <strong>of</strong><br />
water, left for some hours, and filtered at the pump. The material<br />
on the funnel is washed with a little water. Yield 15-16 g.<br />
Pyrrole from Ammonium Mucate. 3 —Mucic acid (15 g.) is dis-<br />
1 M. Heidelberger, Advanced <strong>Laboratory</strong> Manual <strong>of</strong> <strong><strong>Org</strong>anic</strong> <strong>Chemistry</strong>, New<br />
York, 1923, p. 76.<br />
2 Tollens and Kent, Annalen, 1885, 227, 222.<br />
3 Schwanert, Annalen, 1860, 116, 271 ; see also Kiotinsky, Ber., 1909, 42, 2506.
394 OCTA-ACBTYLCBLLOBIOSB<br />
solved in a basin in 15 c.c. <strong>of</strong> 20 per cent ammonia solution and the<br />
solution is evaporated to dryness. The ammonium mucate is stirred<br />
with 20 c.c. <strong>of</strong> glycerol in a distilling flask and the mixture heated.<br />
At 170° the reaction begins and the bulk <strong>of</strong> the pyrrole distils between<br />
180° and 210°. (If the temperature is raised to 300° a little<br />
more pyrrole is obtained.) The substance is dissolved in a little<br />
ether, dried, and fractionated. Boiling point <strong>of</strong> pure pyrrole 131°.<br />
Yield 2-3 g.<br />
A splinter <strong>of</strong> pine wood which has been dipped in concentrated<br />
hydrochloric acid is coloured red by the vapour from a boiling mixture<br />
<strong>of</strong> pyrrole and water<br />
7. OCTA-ACETYLCELLOBIOSE AND CELLOBIOSE<br />
Octa-acetylcellobiose. 1 —Pure cotton wool (20 g.) is added in<br />
portions with good stirring to a cooled mixture (about -10°)<br />
<strong>of</strong> acetic anhydride (75 c.c.) and concentrated sulphuric acid<br />
(8 c.c.) (use a wide-mouthed flask with a ground joint). The temperature<br />
<strong>of</strong> the liquid during this time must not exceed 10°. From<br />
time to time the mass, which gradually liquefies, is pressed with a<br />
glass rod until, after a few hours a viscous solution is formed. The<br />
tightly closed flask is then placed in a thermostat at 30°. After<br />
about five days the solution becomes coloured and crystals <strong>of</strong> cellobiose<br />
acetate begin to separate. During the succeeding five days the<br />
separation <strong>of</strong> crystals increases greatly. After the flask has been<br />
placed in the ice-chest the deposition <strong>of</strong> crystals is completed in five<br />
more days. Now filter the contents <strong>of</strong> the flask at the pump, and<br />
wash with a little cold glacial acetic acid until the wash liquor passing<br />
through is colourless (the wash liquor is not to be combined with the<br />
mother liquor). In order to remove completely adherent sulphuric<br />
acid or sulpho-acetic acid the crystalline mass is suspended in<br />
water for several hours and finally dried at 70°. The yield <strong>of</strong><br />
already rather pure cellobiose acetate amounts, on the average,<br />
to 11-12 g.<br />
For recrystallisation the cellobiose acetate is dissolved in four or<br />
five times its weight <strong>of</strong> chlor<strong>of</strong>orm, filtered, and the solution treated<br />
with three volumes <strong>of</strong> methanol. After boiling the mixture for a<br />
short time, the cellobiose acetate crystallises on cooling in beautiful<br />
1 Oat, Annakn, 1913, 398, 332; K. Hess and H. Friese. Annalen, 1927, 456, 49.
SOME KBMAKKS ON CAKBOHYDKATBS 395<br />
needles. Melting point 220°-222°. Specific rotation + 42° (chlor<strong>of</strong>orm).<br />
The yield can be increased by working up the mother liquor.<br />
Cellobiose. 1 —Dissolve 10 g. <strong>of</strong> the acetyl compound in 20 c.c. <strong>of</strong><br />
chlor<strong>of</strong>orm and cool strongly in a freezing mixture. With continued<br />
cooling and vigorous shaking add to the solution 0'5 g. <strong>of</strong> sodium<br />
dissolved in 25 c.c. <strong>of</strong> absolute methyl alcohol and previously strongly<br />
cooled also. At first a clear solution is formed but very soon a<br />
gelatinous addition compound with sodium ethoxide separates.<br />
After five minutes decompose this compound by dropping in icewater.<br />
Now transfer the reaction mixture to a small separating<br />
funnel and rapidly evaporate 1-2 c.c. <strong>of</strong> the chlor<strong>of</strong>orm layer on a<br />
large watch glass. A small residue only should remain—a sign that<br />
the hydrolysis has been successful. Run <strong>of</strong>f the chlor<strong>of</strong>orm, neutralise<br />
the aqueous solution with acetic acid and evaporate in a vacuum<br />
until syrupy. Part <strong>of</strong> the disaccharide crystallises at this stage.<br />
Mix the syrup with 25 c.c. <strong>of</strong> absolute alcohol, so precipitating the<br />
cellobiose in colourless crystalline form. Leave over night, filter at<br />
the pump; wash with a little absolute alcohol and dry in a vacuum<br />
desiccator. Yield 3-4 g.<br />
SOME REMARKS ON CARBOHYDRATES (WITH REFERENCE<br />
TO SECTIONS 2-7)<br />
Two disaccharides have been hydrolysed and in each case the more<br />
readily crystallisable sugar has been isolated—d-glucose from cane sugar,<br />
i-galactose from lactose. The hydrolysis <strong>of</strong> bioses, by cleavage at the<br />
oxygen bridge, is biologically accelerated by the catalytic action <strong>of</strong><br />
specific enzymes (invertase, lactase). The more universal hydrolysis<br />
by acids is a unimolecular reaction and its velocity is proportional to<br />
the hydrogen ion concentration.<br />
The highly polymerised compound cellulose is broken down into<br />
its octa-acetyl disaccharide cellobiose by " acetolysis " (Franchimont,<br />
Skraup, Ost). The bioses belong to the important group <strong>of</strong> glucosides.<br />
The isomerism <strong>of</strong> a- and j8-glucose is to be attributed to the spatially<br />
different arrangement <strong>of</strong> the H and OH-groups attached to the asymmetric<br />
carbon atom 1. This atom is asymmetric in the cyclic " lactol "<br />
formula (Tollens). The mutarotation <strong>of</strong> the sugars, i.e. the gradual<br />
change to the final stationary value <strong>of</strong> the optical rotation, is to be<br />
explained by an equilibrium occurring in solution between the various<br />
1 G. Zemplen, Ber., 1926, 59, 1258.
396 CONSTITUTION OF BIOSBS<br />
^{Homeric forms, which equilibrium is attained more or less rapidly but<br />
not instantaneously.<br />
Since a-glucose increases the conductivity <strong>of</strong> solution <strong>of</strong> boric acid p<br />
more than does the j8-compound 1 it is assumed that the OH group at Cj<br />
is in the cw-position to that at C2 as is shown in the following formulae.<br />
The best known example <strong>of</strong> an acid complex <strong>of</strong> this type containing<br />
esterified boric acid is the glycerol compound. It is well known that<br />
in the presence <strong>of</strong> glycerol, boric acid, although in itself a very weak acid,<br />
can be titrated. According to Boeseken the complex acid has the following<br />
constitution:<br />
HC x0<br />
H.<br />
7 0—CH<br />
CH2OH CH.OH<br />
a Of ring late closely the related aldohexoses to have that <strong>of</strong> come pyrone to be and considered<br />
betwen C^ and having<br />
caled pyranoses. C5 (Haworth). The For labile this y- reason or ^-sug they<br />
isomers Tolens (" with furanoses the bridge betwen Cj "). and These C4 as are in<br />
produced during celular metabolism (fermentation, oxidative b<br />
tion <strong>of</strong> sugars). A coresponding view is held concerning d<br />
<strong>of</strong> fructose (cf. W. N. Haworth, Helv. Ghi<br />
H OHHO H [HO] H [H] OH<br />
HCOH HCOH Hi<br />
HOCH 0HOCH<br />
0HOC<br />
HCOH HCOH<br />
HL<br />
!OH H 0<br />
CH2OH<br />
-COH<br />
a-tf-glucose CH2OH /3-d-glucose 2<br />
HCOH<br />
HOCH<br />
0 HCOH<br />
a- CH2OH HCOH<br />
1 and /3-A-glucos —CH2 d-fructose e<br />
Merwein, Boeseken, Annalen, Ber., 1913, 46, 1927, 2612 45, ; 27 Rec. ; 1929, t<br />
power <strong>of</strong> weak electrolytes by formation <strong>of</strong> complexes.<br />
4
SOME KBMAKKS ON CAKBOHYDKATBS<br />
A hexagonal formula is especially instructive :<br />
—CH2OH<br />
2<br />
H H<br />
a-d-glueose<br />
Corresponding to the two structurally isomeric forms <strong>of</strong> glucose and<br />
other monoses there are also two types <strong>of</strong> glucosides, each <strong>of</strong> which exists<br />
in two enantiomorphs. All the four ethyl glucosides are known.<br />
The a-glucosides are especially easily hydrolysed by yeast (invertase,<br />
maltase), the j8-glucosides by emulsin, the enzyme <strong>of</strong> bitter almonds.<br />
Accordingly, the biologically important bioses such as sucrose and<br />
maltose belong to the a-series, whilst lactose belongs to the j8-series.<br />
In the same way the biose <strong>of</strong> amygdalin has been recognised as a<br />
P-glucosido-fi-glucose, i.e. gentiobiose (R. Kuhn, Haworth, Hudson).<br />
Helferich has recently succeeded in synthesising this sugar.<br />
The investigation <strong>of</strong> the constitution <strong>of</strong> the bioses has made considerable<br />
progress during the last decade, chiefly through the work <strong>of</strong> British<br />
chemists (Irvine, Haworth, and others). The principle <strong>of</strong> the method<br />
is as follows : the free OH-groups <strong>of</strong> the biose are fixed by methylation,<br />
the octa-methylated molecule is then broken at the glucoside bridge<br />
and the structures <strong>of</strong> the methylated monoses are determined. The<br />
formulae which are at present attributed to the most important bioses<br />
are given below.<br />
HC- ~O CH.OH<br />
HCOH HJ—<br />
HOCH 0 HOCH<br />
HCOH<br />
1I<br />
0<br />
HCOH<br />
HI HC<br />
3H2OH CH2OH<br />
Sucrose<br />
HO H<br />
Maltose<br />
397
398 CONSTITUTION OF BIOSBS<br />
HC ^ 0 CH,OH<br />
Lactose<br />
According to Haworth cellobiose differs from maltose only in having<br />
the j8-glucosidal configuration. Lactose and cellobiose are built up in<br />
identical fashion and differ only in their monose components. Gentiobiose<br />
is a ^-biose ; the common oxygen bridge, however, is attached at<br />
C6. The formulae show at the same time the configurations <strong>of</strong> the constituent<br />
monoses.<br />
The fundamental principles governing the spatial isomerism <strong>of</strong> the<br />
simple sugars and the theoretical and experimental work <strong>of</strong> Emil Fischer<br />
cannot be dealt with here. Those who are not already familiar with<br />
the subject should at once fill this gap in their knowledge; they are<br />
emphatically advised to use space models.<br />
Those bioses in which the aldehydic (cyclo-acetal) carbonyl group is<br />
free have a reducing action (on Fehling's solution).<br />
Experiment.-—Boil samples <strong>of</strong> both sucrose and lactose with<br />
Fehling's solution.<br />
See p. 298 for information about the production <strong>of</strong> the osazones <strong>of</strong><br />
the simple sugars. The osazones <strong>of</strong> rf-glucose, rf-fructose, and rf-mannose<br />
are identical.<br />
The number <strong>of</strong> synthetic bioses is increasing ; among natural bioses<br />
gentiobiose (see above) has been obtained synthetically from d-glucose<br />
by the action <strong>of</strong> emulsin (Bourquelot). Attempts at synthesis with the<br />
bromoacetyl-sugars do not succeed because the desired OH-group <strong>of</strong> the<br />
second molecule is not attacked. The bromoacetyl-sugars are formed,<br />
quite generally, by the action <strong>of</strong> acetyl bromide on the sugars.<br />
The synthesis <strong>of</strong> lactose has been described very recently by A.<br />
Pictet. Helferich has also been successful in synthetic work <strong>of</strong> this<br />
kind.<br />
Of other recent experiments in the chemistry <strong>of</strong> the sugars the preparation<br />
<strong>of</strong> the anhydro-sugar laevoglucosan C6H10O8 by the rapid distillation<br />
<strong>of</strong> starch or cellulose in a vacuum may be mentioned (Pictet).<br />
This interesting compound possibly has the constitution I.
I 0<br />
III<br />
SOME KBMAKKS ON CAKBOHYDKATBS<br />
Br H<br />
/CH C<br />
CH—<br />
II<br />
CH<br />
HOCH 0<br />
HCOH<br />
II<br />
HgC.COOCH<br />
IV<br />
HCO.( I.COCHJ<br />
HCOCOCH3<br />
DH-<br />
H2CO.CO.CH3<br />
HOCH 0<br />
HCOH<br />
CH2OH CH.OH<br />
The adjoining formula II belongs to a-acetobromoglucose (tetraacetyl-a-bromo-d-glucose),<br />
which is also formed from starch (Bergmann)<br />
and cellulose (Karrer, Hess) by the action <strong>of</strong> acetyl bromide.<br />
On boiling with 50 per cent acetic acid and zinc dust, the bromine at<br />
the first carbon atom is replaced by hydrogen, and at the same time<br />
acetic acid is eliminated with the formation <strong>of</strong> a double bond between<br />
carbon atoms 1 and 2. From the resulting compound, the substance<br />
III, glucal C6H10O4 (E. Fischer, Bergmann), is formed by hydrolytic<br />
elimination <strong>of</strong> the other three acetyl groups. Prileschaiev's reaction<br />
with benzoyl peroxide (p. Ill) produces from III the anhydro-sugar IV.<br />
<strong>of</strong> which the 1-2-bridge is very easily broken by water to yield the<br />
glycol group. The main product is then mannose (Bergmann).<br />
What are the products <strong>of</strong> oxidation and reduction <strong>of</strong> the monosaccharides<br />
? Mucic acid, <strong>of</strong> which the preparation from d-galactose<br />
has been described, is optically inactive and incapable <strong>of</strong> resolution,<br />
just like dulcitol, the corresponding hexahydric alcohol. As the formula<br />
shows, the four asymmetric carbon atoms <strong>of</strong> galactose form two<br />
pairs (2, 5 and 3, 4) having the same substituents but opposite arrangement<br />
in space, and when the carbon atoms 1 and 6 become alike, inactive<br />
forms are produced by intramolecular compensation, as in mesotartaric<br />
acid.<br />
0<br />
399
400 GLUCAL.<br />
HCOH<br />
OH<br />
d-Galactose<br />
MUCIC ACID. DULCITOL<br />
HCOH<br />
al<br />
HOCH<br />
HOCH<br />
si<br />
HCOH<br />
el COOH<br />
Mucic acid<br />
CH2OH<br />
HCOH<br />
HOCH<br />
HOCH<br />
HCOH<br />
CH2OH<br />
Dulcitol<br />
Like the pentoses, mucic acid loses three molecules <strong>of</strong> water and is<br />
converted, as described on p. 386, into derivatives <strong>of</strong> furane ; with concentrated<br />
hydrochloric acid the product isfurane-a : d-dicarbozylic acid.<br />
Dry distillation yields furane-a-carboxylic or pyromucic acid.<br />
HOCH- -HCOH<br />
CH—CH<br />
I II II —><br />
HOOCHCOH HOCH COOH HOOC.C C.COOH<br />
0 0<br />
CH—CH<br />
I I •<br />
CH C.COOH<br />
Pyrogenic decomposition <strong>of</strong> mucic acid in the manner indicated above<br />
but in presence <strong>of</strong> NH3 yields pyrrole, the important unit from which<br />
chlorophyll and blood pigments are built up (see p. 407). The oxygen<br />
bridge in the furane ring is replaced by NH—a general reaction <strong>of</strong> heterorings<br />
containing oxygen.<br />
Ascorbic acid, which is closely related to the sugars and is no doubt<br />
derived from them in the metabolism <strong>of</strong> the cells <strong>of</strong> plants, has been<br />
shown to be identical with vitamin- G (Szent-Gyorgyi). It has the constitution<br />
<strong>of</strong> a lactone <strong>of</strong> a-keto-Z-gulonic acid (W. N. Haworth, T.<br />
Reichstein) :<br />
HO.C^C.OH<br />
HOH2C.H(H0)C-<br />
-CH CO<br />
Monographs: Tollens-Elsner, Kurzes Lehrbuch der Kohlenhydrate,<br />
Leipzig, 1935 ; W. N. Haworth, The Constitution <strong>of</strong> Sugars, London,<br />
1929 ; Kurt Hess, Die Ghemie der Zellulose und ihrer Begleiter, Leipzig,<br />
1928 ; H. Staudinger, Die hochmolekularen organischen Verbindungen,<br />
Berlin, 1932.
SACCHAKIFICATION OF STAKCH 401<br />
8. SACCHARIFICATION OF STARCH AND ALCOHOLIC<br />
FERMENTATION<br />
Saccharification.—Potato starch 1 (100 g.) is made into a thin<br />
sludge by stirring with water and then poured slowly into an enamelled<br />
jar (capacity 2-5 1.) containing 1500 c.c. <strong>of</strong> boiling water,<br />
which is kept vigorously stirred throughout with a wooden spoon.<br />
To the thick homogeneous glassy material so obtained (after coolmg<br />
to 40°) there is added one-third <strong>of</strong> a filtered extract, freshly prepared<br />
by digesting 15 g. <strong>of</strong> coarsely ground kiln malt with 100 c.c. <strong>of</strong> water<br />
at 35°-40° for one hour.<br />
The saccharification, which should be carried out at about 40°,<br />
is accelerated by stirring and is complete in about an hour. Its<br />
course is followed by removing 5 c.c. <strong>of</strong> the solution a quarter <strong>of</strong> an<br />
hour after the malt extract has been added and determining in this<br />
sample, by the method <strong>of</strong> Willstatter and Schudel, 2 the amount <strong>of</strong><br />
maltose formed (see below). After thirty minutes more the determination<br />
is repeated.<br />
The Sugar Determination.—Dilute the 5 c.c. sample in a measuring<br />
flask to 25 c.c. and pour 10 c.c. <strong>of</strong> this diluted solution into 25 c.c.<br />
<strong>of</strong> 0-1 N-iodine solution. Then add 40 c.c. <strong>of</strong> 0-1 N-sodium hydroxide<br />
solution (free from alcohol) and leave for twenty minutes. Make faintly<br />
acid with dilute sulphuric acid and titrate back with 0-1 N-sodium<br />
thiosulphate solution. One equivalent <strong>of</strong> iodine corresponds to 0-5<br />
mole <strong>of</strong> reducing biose, or 1 c.c. <strong>of</strong> 0-1 N-iodine solution to 17-1 mg.<br />
<strong>of</strong> maltose. What is the course <strong>of</strong> the reaction ?<br />
When the consumption <strong>of</strong> iodine is the same in two successive<br />
tests and a sample <strong>of</strong> the mixture is no longer coloured by iodine<br />
the saccharification is complete. Usually 75-80 per cent <strong>of</strong> the<br />
starch taken is converted into sugar. The rest <strong>of</strong> the starch is only<br />
broken down into dextrins, which are, however, also saccharified in<br />
the course <strong>of</strong> the subsequent fermentation. The volume <strong>of</strong> the<br />
mash is measured in a cylinder, and from the result <strong>of</strong> the final<br />
maltose titration the sugar content is calculated. For the CO2determination<br />
10 c.c. are retained (cf. p. 402).<br />
Fermentation.—The solution is next transferred to a roundbottomed<br />
flask (capacity 3 1.) for fermentation. To set this going 10 g.<br />
1 If it is desired to start from potatoes (500 g.), they must be heated in a digester<br />
under 2-3 atmospheres pressure, since simple boiling till s<strong>of</strong>t does not produce a<br />
breakdown sufficient for complete saccharification.<br />
» Ber., 1918, 51, 780.<br />
2D
402 ALCOHOLIC FBKMBNTATION<br />
<strong>of</strong> baker's yeast made into a dough with water are added after 3 g.<br />
<strong>of</strong> dihydrogen ammonium phosphate have been dissolved in the<br />
mash. The flask is now provided with a small two-bulb trap containing<br />
a little water and well shaken from time to time; after<br />
fermentation has set in it is allowed to proceed to completion for<br />
two to three days in a warm room. As the process nears its end<br />
the water in the seal hardly moves, or not at all. The alcohol is<br />
now distilled through an efficient column (Kaschig rings), downward<br />
condenser, and adapter into a filter flask. Barely half <strong>of</strong> the<br />
liquid is distilled. Then the distillate is transferred to a smaller<br />
flask and distillation is twice repeated as before until the final volume<br />
collected is about 200 c.c. From the specific gravity determined<br />
with a hydrometer at 15° the alcohol content is found.<br />
At 15° the specific gravity <strong>of</strong> 10 per cent alcohol (by volume) is<br />
0-9857 and that <strong>of</strong> 30 per cent alcohol 0-9646. Between these two contents<br />
the specific gravity decreases nearly linearly by 0-0010 for each<br />
1 per cent by volume, so that from the specific gravity found the concentration<br />
<strong>of</strong> the alcohol obtained can be calculated without the use <strong>of</strong><br />
a table.<br />
In the aqueous-alcoholic distillate having a volume <strong>of</strong> about<br />
200 c.c. about 70 c.c. or 56 g. <strong>of</strong> alcohol will be found. The yield<br />
<strong>of</strong> alcohol approaches the theoretical value and should amount to<br />
about 20 per cent more than would be calculated from the maltose<br />
determination just carried out, since the latter does not, <strong>of</strong> course,<br />
take into account the additional sugar produced during the fermentation<br />
by " diastatic after efEect ".<br />
Work out the balance for the whole process, taking into consideration<br />
the number <strong>of</strong> litres <strong>of</strong> CO2 formed.<br />
In order to obtain the alcohol in the pure state the final distillate<br />
is dropped from a tap funnel into a distilling flask containing 700 g.<br />
<strong>of</strong> quicklime. The flask is connected to a downward condenser<br />
and is heated in an oil bath so that the alcohol distils.<br />
Determination <strong>of</strong> CO2.—Dilute 10 c.c. <strong>of</strong> the mash to 25 c.c. in a<br />
measuring flask and transfer 10 c.c. <strong>of</strong> the diluted liquid by means <strong>of</strong> a<br />
pipette to a small distilling flask which is directly connected to a nitrometer.<br />
To the solution add about 0-2 g. <strong>of</strong> yeast made into a cream<br />
with a little water and then at once displace the air by passing in<br />
carbon dioxide from above through a tube which does not dip into the<br />
liquid. Close the delivery tube by means <strong>of</strong> stop-cock or spring clip,<br />
fill the nitrometer with water saturated with carbon dioxide, and allow
MECHANISM OF FBKMBNTATION 403<br />
fermentation to proceed until the volume <strong>of</strong> gas evolved ceases to<br />
increase. Finally, reduce the volume found to 0° and 760 mm. and compare<br />
the result with the yield <strong>of</strong> alcohol and with the result <strong>of</strong> the maltose<br />
determination, making allowance for the additional saccharification.<br />
The chemical course <strong>of</strong> alcoholic fermentation, which has already<br />
been the subject <strong>of</strong> investigation for more than a century, has been<br />
explained chiefly by the work <strong>of</strong> C. Neuberg and G. Embden. E.<br />
Biichner proved that zymase, the enzyme complex <strong>of</strong> yeast, can be<br />
separated from the living cells.<br />
Shortly summarised, the process may be regarded as resulting from<br />
a series <strong>of</strong> successive hydrogenation and dehydrogenation reactions<br />
similar to that <strong>of</strong> Cannizzaro (p. 220), and taking place as follows:<br />
d-glucose in the form <strong>of</strong> a phosphoric ester first decomposes into two<br />
molecules <strong>of</strong> glyceraldehyde-phosphoric acid:<br />
C6H10O4(PO4H)2 —> 2CH2.CHOH.CHO<br />
O.PO3H2<br />
This aldehyde undergoes " dismutation " to glycerophosphoric acid<br />
and phosphoglyceric acid (half and half):<br />
2CH2.CHOH.CHO +H '° CH2.CHOH.CH2OH<br />
OPO3H2<br />
O.PO3H2<br />
CH2.CHOH.CO2H<br />
O.PO3H2<br />
The next stage leads to the transformation <strong>of</strong> the phosphorylated<br />
glyceric acid into pyruvic acid, which is then converted into acetaldehyde<br />
and CO2 by the enzyme carboxylase. As soon as the acetaldehyde is<br />
formed it enters into enzymic reaction with the phosphorylated glyceraldehyde<br />
which is dehydrogenated to the acid while the aldehyde<br />
becomes ethyl alcohol.<br />
CH2.CHOH.CH(OH)2 + CH3.C=0 > CH2.CHOH.CO2H + CH3.CH2OH<br />
I H 1<br />
OPO3H2<br />
O.PO3H2<br />
In muscle the transformation <strong>of</strong> rf-glucose proceeds via lactic acid.<br />
More detailed information about enzymes will be found in Oppenheimer<br />
and Kuhn, Lehrbuch der Enzyme, Leipzig, 1927 ; J. B. 8. Haldane,<br />
Enzymes, London, 1930.
404 AKGININE<br />
9. d-ARGININE HYDROCHLORIDE FROM GELATIN 1<br />
d-Arginine Flaviante.—Gelatin (100 g.) is boiled vigorously<br />
under reflux for eight to ten hours in a half-litre flask with 100 c.c.<br />
<strong>of</strong> 36 per cent hydrochloric acid (d. 1-19). After the liquid has<br />
cooled it is diluted to about 500 c.c, treated with 5 c.c. <strong>of</strong> glacial<br />
acetic acid and then with 33 per cent sodium hydroxide solution<br />
until no longer acid to Congo paper : then a further 6 c.c. <strong>of</strong> glacial<br />
acetic acid are added. The liquid is filtered if necessary, and a hot<br />
solution <strong>of</strong> 20 g. <strong>of</strong> flavianic acid (naphthol yellow S, see p. 195) in<br />
100 c.c. <strong>of</strong> water is added. After a quarter to half an hour the flavianate<br />
begins to separate. The mixture is left for one to two days and<br />
then filtered at the pump. In order to remove any flavianic acid<br />
which is precipitated at the same time, the solid is ground twice with<br />
200 c.c. portions <strong>of</strong> cold water and filtered at the pump each time.<br />
Yield 18-22 g. d-Arginine flavianate blackens above 200° and decomposes<br />
at 275°.<br />
Monohydrochloride <strong>of</strong> d-Arginine.—The flavianate is suspended<br />
in 100 c.c. <strong>of</strong> hot water in a large mortar and well ground with a<br />
solution <strong>of</strong> 40 g. <strong>of</strong> barium hydroxide dissolved in the necessary<br />
amount <strong>of</strong> hot water. The barium flavianate which is precipitated<br />
is collected at the pump while the mixture is still hot, ground again<br />
with a hot solution <strong>of</strong> 8 g. <strong>of</strong> barium hydroxide in 200 c.c. <strong>of</strong> water,<br />
and once more separated at the pump. A rapid current <strong>of</strong> carbon<br />
dioxide is at once passed into the combined filtrates until the reaction<br />
is slightly acid ; the barium carbonate which is precipitated<br />
is removed by filtration at the pump and washed well with water.<br />
After the filtrate has been concentrated to 100-150 c.c. on the water<br />
bath and filtered from more precipitated barium carbonate, it is<br />
made acid to Congo red by addition <strong>of</strong> concentrated hydrochloric<br />
acid (3-4 c.c.) and left for a short time. Some more flavianic acid<br />
is precipitated from the cold solution on scratching, and is removed<br />
by filtration. The filtrate is decolorised by boiling for a short time<br />
with animal charcoal and filtered once more. The almost colourless<br />
filtrate is made faintly alkaline with ammonia and evaporated to<br />
dryness. In this way a mixture <strong>of</strong> arginine hydrochloride and<br />
ammonium chloride is obtained. The mixture is dissolved in as<br />
little hot water as possible, and the hot solution is diluted with hot<br />
96 per cent alcohol until a distinct turbidity appears. As the liquid<br />
1 Kossel and Gross, Z. physiol. Chem., 1924, 135, 167 ; Felix and Dirr, Z.<br />
physiol. Chem., 1928, 176, 38.
CAFFEINE FKOM TEA 405<br />
cools the argmme hydrochlonde is almost quantitatively precipitated<br />
in sheaves <strong>of</strong> prisms which are recrystalhsed m the same way<br />
Yield 7-8 g<br />
rf-Arginine monohydrochlonde smters at 218° and decomposes<br />
with copious frothing at 235°<br />
The flavianic acid can be recovered from its sparingly soluble barium<br />
salt as follows Decompose the salt with a slight excess <strong>of</strong> hot 20 per<br />
cent sulphuric acid, filter at the pump while hot, add some concentrated<br />
hydrochloric acid to the clear filtrate, and allow the free sulphonic acid<br />
to crystallise<br />
The method given by Bergmann 1 for the preparation <strong>of</strong> arginine<br />
may also be recommended here<br />
10 CAFFEINE FROM TEA<br />
In the simplified extraction apparatus (Fig 27 on p 35) 100 g<br />
<strong>of</strong> finely powdered tea or tea dust are extracted for eight hours with<br />
400 c c <strong>of</strong> alcohol The alcoholic extract is then added to a suspension<br />
<strong>of</strong> 50 g <strong>of</strong> magnesium oxide in 300 c c <strong>of</strong> water, and the whole<br />
is evaporated to dryness on the steam bath m a porcelam basm<br />
with frequent stirrmg The pulverulent residue is boiled once with<br />
500 c c and then three times with 250 c c <strong>of</strong> water and filtered while<br />
hot at the pump<br />
After 50 c c <strong>of</strong> dilute sulphuric acid have been added to the<br />
combined nitrates, they are concentrated to about one-third <strong>of</strong> their<br />
volume, filtered if necessary while hot from the flocculent precipitate<br />
which occasionally forms, and then extracted five times with 30 c.c<br />
portions <strong>of</strong> chlor<strong>of</strong>orm<br />
The pale yellow chlor<strong>of</strong>orm solution is decolorised by shaking,<br />
first with a few cubic centimetres <strong>of</strong> sodium hydroxide solution, then<br />
with the same volume <strong>of</strong> water, and is evaporated to dryness The<br />
residue <strong>of</strong> crude caffeine is recrystallised from a little hot water<br />
Yield 2 0-2 5 g. S<strong>of</strong>t, flexible, silky needles containing one molecule<br />
<strong>of</strong> water <strong>of</strong> crystallisation<br />
In the same way theobromme can be isolated from cocoa powder<br />
which has previously been freed from fat with ether or petrol ether<br />
in an extractor Prepare caffeine from the theobromme by methylation<br />
according to the method <strong>of</strong> H Blitz 2<br />
1 Z physiol Chem, 1926, 152, 293<br />
2 Annalen, 1917, 413, 190 The reaction was first carried out by A Strecker<br />
(Annalen, 1861, 118, 170)
406 NICOTINE<br />
11. NICOTINE FROM TOBACCO EXTRACT 1<br />
Commercial tobacco extract (300 c.c, d. 1-8), which can also be<br />
prepared by concentration <strong>of</strong> the faintly acidified dilute extract to<br />
be had in any cigar factory, is made strongly alkaline with concentrated<br />
sodium hydroxide solution. Steam is passed through the<br />
hot solution and the free nicotine bases pass over. About 1-5 1. <strong>of</strong><br />
distillate are collected, made faintly acid to Congo red with solid<br />
oxalic acid (a weighed quantity), and concentrated to a syrup. When<br />
the syrup cools nicotine oxalate contaminated with some ammonium<br />
oxalate separates. The crystalline sludge is transferred to a separating<br />
funnel into which is poured rather more potassium hydroxide<br />
solution (1:1) than corresponds to the oxalic acid used. Heat is<br />
developed, and after some time the crude nicotine rises to the surface<br />
as a brown oil, which is separated from the cooled mixture by repeated<br />
extraction with ether. The concentrated ethereal solution<br />
is dried with a few pieces <strong>of</strong> solid potassium hydroxide and then the<br />
ether is evaporated. The residue is fractionally distilled in a vacuum<br />
from a small Claisen flask. Since rubber stoppers are attacked by<br />
nicotine air-tight corks are used instead.<br />
By repeated distillation <strong>of</strong> the higher boiling fraction the pure<br />
base is obtained as a colourless liquid <strong>of</strong> boiling point 114°/10 mm.,<br />
120°/14 mm. At atmospheric pressure nicotine boils without decomposition<br />
at 240°. The yield varies from 4 to 6 g.<br />
The specimen turns brown very soon if exposed to the air, and<br />
must be kept in a sealed glass tube.<br />
From a sample prepare the dimethiodide thus : Dissolve the base in<br />
a little methyl alcohol and warm the solution with about three parts <strong>of</strong><br />
methyl iodide. Recrystallise from a little methyl alcohol.<br />
Oxidise some nicotine to nicotinic acid with permanganate.<br />
Most alkaloids are isolated from plant extracts by conversion into the<br />
difficultly soluble salts which they form with complex acids such as<br />
hexachloroplatinic acid, chlorauric acid, phosphotungstic acid, hydr<strong>of</strong>errocyanic<br />
acid, Reinecke's acid, etc. Perchloric acid, picric acid, flavianic<br />
acid, mercuric chloride, iodine in potassium iodide are also used.<br />
Study the syntheses <strong>of</strong> nicotine (Pictet, Karrer). What is tropine,<br />
and what alkaloids are derived from it ?<br />
1 Laiblin, Annalen, 1879, 196, 130.
HABMIN FKOM OX BLOOD 407<br />
12. HAEMIN FROM OX BLOOD<br />
Glacial acetic acid (3 1.), to which 5 c.c. <strong>of</strong> saturated brine have<br />
been added, is heated to 100° in a four-litre round-bottomed flask<br />
on a sand bath or conical (Babo) air 1 bath. During the course<br />
<strong>of</strong> twenty to thirty minutes a litre <strong>of</strong> defibrinated blood filtered<br />
through a linen cloth is dropped in a thin stream with frequent<br />
shaking from a funnel into the hot solvent without interrupting the<br />
heating. The end <strong>of</strong> the delivery tube <strong>of</strong> the funnel reaches below<br />
the neck <strong>of</strong> the flask and the blood is not allowed to come into contact<br />
with the walls as it flows in; the temperature should not fall<br />
below 90 °. After the blood has been added, the liquid is kept gently<br />
boiling for a quarter <strong>of</strong> an hour longer ; the bulk <strong>of</strong> the haemin will<br />
separate in the form <strong>of</strong> shining crystals. The mixture is cooled to<br />
40°-50° 2 and filtered at this temperature. The haemin is washed<br />
successively with 50 per cent acetic acid, water, alcohol, and ether.<br />
Dark crystals having a high surface lustre and great purity. Yield<br />
3-5-4-0 g.<br />
In the blood pigment, haemoglobin, the coloured component which<br />
is separated as haemin in the manner described above is combined with<br />
a complicated protein component known as globin. According to Hans<br />
Fischer, haemin has the composition C34H32O4N4FeCl. This compound<br />
in the form <strong>of</strong> the so-called Teichmann crystals serves for the microscopic<br />
detection <strong>of</strong> blood.<br />
It is also the starting point for the fundamental degradation experiments<br />
which have paved the way to the synthesis <strong>of</strong> this important<br />
substance (Nencki, Kiister, Piloty, Willstatter, H. Fischer).<br />
When haemin is reduced with hydriodic acid it yields a mixture <strong>of</strong><br />
substituted pyrroles and pyrrole carboxylic acids, namely :<br />
.UQO.O O.Oo-ti-K xigO.U O.O2-H5 xioO.O O.Oo-ti-K<br />
II II II II II II<br />
H3C.C CH , HC C.CH3 , H3C.C C.CH3 ,<br />
NH NH NH<br />
Haemopyrrole Cryptopyrrole Phyllopyrrole<br />
1<br />
Process <strong>of</strong> Schalfeiev. Details given by Nencki and Zaleski, Z. physiol.<br />
Chem., 1900, 30, 390; Willstatter and Stoll, Untersuchungen liber Chloroph<br />
Berlin, 2 1913, p. 399.<br />
According to H. Fischer in C. Oppenheimer's Handbuch der Biochemie, vol. i.<br />
p. 357, 1923.
408 SUBSTITUTED PYRROLES<br />
CC CC2-Hg HgC.C<br />
II II II II<br />
HC CH , H3C.C CH<br />
COOH,<br />
NH NH<br />
3 : 4-Methylethylpyrrole Haemopyrrole carboxylic acid<br />
H3C.C C.CH2.CH2 H3C.C C.CH2.CH2<br />
|| || COOH, || || COOH.<br />
HC C.CHg H3C.C C.CHg<br />
\ / V<br />
NH NH<br />
Cryptopyrrole carboxylic acid Phyllopyrrole carboxylic acid<br />
All these degradation products have also been obtained synthetically,<br />
chiefly by H. Fischer. On oxidation, haemin yields derivatives <strong>of</strong><br />
maleic imide (W. Kuster) corresponding to the fact that pyrrole itself<br />
can be oxidised to this substance.<br />
CH—CH CH=CH<br />
II II I I<br />
CH CH —>- CO CO.<br />
NH NH<br />
Thus the imide <strong>of</strong> methylethylmaleic acid (I) corresponds to the<br />
pyrroles, and the so-called haematinic acid (II) to the carboxylic acids<br />
formulated above:<br />
H3C.C==C.C2H5<br />
H3C.C=C.CH2.CH2.COOH<br />
I OC CO , II OC CO<br />
NH NH<br />
As will be seen later, C—C bonds <strong>of</strong> substituents in the a-position<br />
are broken on hydrogenation and so the various pyrrole units are set free.<br />
The porphyrins are pigments <strong>of</strong> this group, which have been freed<br />
from iron ; they are closely related to haemin, and iron in complex<br />
union can be reintroduced into them. Similar porphyrins are also<br />
derived from chlorophyll.<br />
Two natural porphyrins, uroporphyrin C40H38O16N4 and coproporphyrin<br />
C36H38O8N4, have acquired great importance in connection with<br />
the question <strong>of</strong> constitution. These substances tyere first isolated by<br />
Hans Fischer from the urine and faeces <strong>of</strong> a patient sufEering from deranged<br />
porphyrin metabolism; they are also formed in traces during<br />
normal metabolism. Uroporphyrin is an octa-, coproporphyrin a tetracarboxylic<br />
acid. Both are converted by thermal decarboxylation into<br />
the oxygen-free aetioporphyrin C32H38N4, a substance which Willstatter<br />
had obtained from haemin.<br />
With the synthesis <strong>of</strong> haemin (H. Fischer, 1929) our knowledge <strong>of</strong> the
PKOTOPOKPHYKIN 409<br />
chemistry <strong>of</strong> the coloured components <strong>of</strong> the blood pigment has been<br />
made complete. The iron-free parent substance <strong>of</strong> haemin, protoporphyrin,<br />
has the following structure :<br />
CH<br />
CH<br />
CO2H CO2H<br />
(b) (a)<br />
Protoporphyrin<br />
The starting material for the synthesis was the iron compound <strong>of</strong><br />
deuteroporphyrin in which c and d = H. By means <strong>of</strong> the Priedel-Crafts<br />
reaction (SnCl4 in place <strong>of</strong> A1C13), acetyl groups were introduced at<br />
c and d, the diketone formed was reduced to the glycol (haematoporphyrin,<br />
c and d =CH0H.CH3), and the latter converted into protoporphyrin<br />
with elimination <strong>of</strong> water.<br />
Fundamentally the synthesis <strong>of</strong> the porphyrins consists in condensation<br />
(by fusion) <strong>of</strong> two suitable " pyrromethines " with elimination <strong>of</strong><br />
HBr and simultaneous dehydrogenation. The formulae represent this<br />
process in the case <strong>of</strong> deuteroporphyrin :<br />
CH CH2.CH2.CO2H<br />
CH2.CH2.CO2H
410 CHROMATOGRAPHIC ADSORPTION<br />
In haemin the iron is combined thus : The two hydrogen atoms <strong>of</strong><br />
the NH-groups <strong>of</strong> its porphyrin are replaced by two principal valencies<br />
<strong>of</strong> the metal which is also united in complex combination to the two<br />
other N-atoms (as in the complex nickel compound <strong>of</strong> dimethylglyoxime<br />
according to Tschugaev). Then the resulting complex cation combines<br />
with Cl' or another univalent anion to form a salt.<br />
In chlorophyll iron as complex-forming metal is replaced by magnesium<br />
(Willstatter). The structure <strong>of</strong> chlorophyll differs from that <strong>of</strong><br />
haemin as follows. In chlorophyll one propionic acid chain (a) in<br />
oxidised form has condensed with a methine carbon atom to form a<br />
cyclopentane ring which takes the position at (c) <strong>of</strong> the vinyl ethyl.<br />
Further the two carbonyl groups are esterified and one <strong>of</strong> the four<br />
pyrrole rings is partially hydrogenated<br />
CH CHO<br />
H<br />
Pht x O-CO OCH3~<br />
Chlorophyll-a (according to H. Fischer)<br />
Chromatographic Adsorption <strong>of</strong> Pigment from Leaves. 2 —Immerse<br />
fresh leaves (3-4) <strong>of</strong> spinach in a mixture <strong>of</strong> 45 c.c. <strong>of</strong> petrol<br />
ether (boiling point 70°), 5 c.c. <strong>of</strong> benzene and 15 c.c. <strong>of</strong> methanol in a<br />
conical flask. Leave for one hour, remove the almost white residue<br />
by nitration at the pump, and wash with the same mixture <strong>of</strong><br />
solvents. Transfer the liquid to a separating funnel and without<br />
shaking remove the methyl alcohol completely by repeated cautious<br />
washing with water. Then dry the solution over sodium sulphate.<br />
For the adsorption use a tube about 18 cm. long and 1 cm. in<br />
diameter having a constriction at the lower end. Drop in a filter-<br />
1 Residue C20H39 <strong>of</strong> the unsaturated alcohol phytol having the constitution<br />
(CH3)2.CH.(CHi!)s.CH(CHs).(CH2)3CH(CHs) (CH2)3.C(CH3): CH.CH20H. For details,<br />
see F. G. Fischer and K. Lowenberg, Annalen, 1928, 464, 69 ; 1929, 475, 183.<br />
2 Cf. p. 14.
GLYCOCHOLIC ACID 411<br />
plate to fit and cover it with a thin pad <strong>of</strong> cotton wool. Now pour in<br />
aluminium oxide (Merck's prepared by Brockmann's method) in<br />
small portions until a layer 2 cm. deep is formed and by tapping and<br />
gently pressing with a thick glass rod which fits the tube, form a<br />
sufficiently compact column. In the same way form on this column<br />
one 4 cm. high <strong>of</strong> calcium carbonate which has been dried at 150°<br />
and above this a column 6 cm. high <strong>of</strong> sieved powdered sugar<br />
(" icing sugar"). Now run in petroleum ether<br />
(boiling point 70°) from a dropping funnel maintaining<br />
gentle suction kept as steady as possible<br />
and follow with the green solution. Immediately<br />
various zones are formed, the upper yellowish<br />
green layer being <strong>of</strong> chlorophyll-b and the bluish<br />
green <strong>of</strong> chlorophyll-a. Below these is a yellow<br />
zone containing xanthophyll. The yellow carotene<br />
is fixed in a small zone by the A12O3 (see Fig. 59).<br />
When all but a small portion <strong>of</strong> the solution<br />
<strong>of</strong> the pigments has run through " develop " the<br />
Sugar<br />
"chromatogram", i.e. separate the zones by<br />
washing with a 4: 1 mixture <strong>of</strong> petroleum ether<br />
and benzene. Check too great extension <strong>of</strong> the<br />
zones by adding petrol ether (boiling point 30-50°).<br />
CaCO,<br />
Now wash with petrol ether, dry with suction in<br />
a current <strong>of</strong> CO2, push out the column with a<br />
suitable glass rod and cut the various zones apart.<br />
Dissolve the pigments with ether containing a little<br />
methanol and examine the absorption spectrum.<br />
These simple operations constitute a clear<br />
demonstration <strong>of</strong> the possibilities <strong>of</strong> the method,<br />
. .<br />
the coloured zones <strong>of</strong> the column forming a<br />
beautiful picture <strong>of</strong> its efficiency. 1<br />
Xantk<strong>of</strong>hyll<br />
. 59<br />
For the preparation <strong>of</strong> chlorophyll in the practical class see the<br />
procedure described by Willstatter and StoU on pages 133 and 138 <strong>of</strong><br />
their book.<br />
13. THE CHIEF CONSTITUENTS OF OX BILE<br />
Glycocholic Acid.—Fresh ox bile (2-0-2-5 1.) is obtained from a<br />
1 It ia recommended that, aa a further example <strong>of</strong> the method, industrial anthracene<br />
ahould be purified aa deacribed by Winteratein, Schon, and Vetter (Z. physiol.<br />
Chem., 1934, 230, 158). Magnificent leafleta having a blue fluoreacence can be<br />
obtained when the hydrocarbon ia purified in thia way.
412 CHOLIC ACID<br />
slaughter-house and a small portion is used for isolating the most<br />
important <strong>of</strong> the conjugated acids <strong>of</strong> the bile, namely, glycocholic add.<br />
In a 750 c.c. separating funnel 250 c.c. <strong>of</strong> the bile are vigorously<br />
shaken with 150 c.c. <strong>of</strong> ether ; then 25 c.c. <strong>of</strong> 4iV-sulphuric acid are<br />
added, and the whole is at once shaken without interruption for<br />
three minutes. After a rather long time-—usually by the next day-—<br />
the glycocholic acid has separated in snow-white needles which form<br />
a voluminous mass at the liquid interface. The crystals are collected<br />
at the pump and washed with a little water and then with ether.<br />
For purification they are dissolved in very little hot alcohol, and<br />
water is added to the solution until turbidity appears.<br />
Occasionally the glycocholic acid does not crystallise from the<br />
acidified bile until several days have elapsed. Frequent shaking has<br />
an accelerating effect. With summer bile the experiment <strong>of</strong>ten fails<br />
because the components <strong>of</strong> such bile crystallise with more difficulty.<br />
As far as experience goes, this has never been the case in winter.<br />
Cholic Acid.-—Commercial potassium hydroxide (200 g.) is added<br />
to fresh ox bile (2 1.) and the mixture is boiled under reflux for<br />
eighteen hours. It is best to use a copper or iron flask, but a large<br />
round-bottomed flask <strong>of</strong> Jena glass heated on a sand bath may also<br />
be employed. After the alkaline liquid has cooled it is transferred to<br />
a filter jar and made just acid to Congo paper by addition <strong>of</strong> hydrochloric<br />
acid (1 part concentrated acid, 2 parts water) which is poured<br />
in with constant stirring by means <strong>of</strong> a stout glass rod. The result<br />
<strong>of</strong> the acidification is that the bile acids and the bile pigment (biliverdin)<br />
are precipitated as a green resinous mass. At first this has the<br />
consistency <strong>of</strong> dough, but after being left for twenty-four hours in the<br />
salt solution it becomes harder, brittle, and crystalline. The hard<br />
material is removed and broken up as far as possible with the fingers<br />
under clean water in a basin. Then the crumbly mass is collected<br />
at the pump and again washed well with water. The crude acids<br />
must now be dried completely before further treatment. At least<br />
eight days are necessary to accomplish this when the substance is<br />
left exposed to the air in a thin layer on filter paper or wood. The<br />
object is more rapidly achieved if the adherent water is removed<br />
in a vacuum desiccator over concentrated sulphuric acid and solid<br />
potassium hydroxide. Ultimately 100-110 g. <strong>of</strong> pale grey-green<br />
substance, which can be powdered to a fine dust, are obtained.<br />
In this condition it is transferred to a conical flask into which<br />
absolute alcohol (a volume equivalent to two-thirds <strong>of</strong> the weight <strong>of</strong>
DBSOXYCHOLIC ACID 413<br />
the solid) is poured and the mixture is shaken well so that the whole<br />
mass is moistened. Already after one day a sludge <strong>of</strong> the readily<br />
crystallisable alcohol compound <strong>of</strong> cholic acid has been formed.<br />
After standing for two days the thick sludge is collected at the pump<br />
on a medium-sized filter plate (5 cm. in diameter), and when the<br />
dark green mother liquor has drained almost completely away the<br />
remainder <strong>of</strong> the crystalline material is washed on to the filter plate<br />
with a little absolute alcohol. Then the crystals are washed with<br />
absolute alcohol until the adherent liquor has been removed and the<br />
liquid which passes through is only pale green in colour. In this<br />
way (after drying on the water bath) 80-85 g. <strong>of</strong> cholic acid, which<br />
is already fairly pure, are obtained. This is equivalent to 70 per<br />
cent <strong>of</strong> the crude precipitate (10 per cent <strong>of</strong> the weight consists <strong>of</strong> the<br />
alcohol <strong>of</strong> crystallisation).<br />
For further purification the crystallised acid is boiled for a quarter<br />
<strong>of</strong> an hour under reflux with methylated spirit (one part by volume<br />
<strong>of</strong> spirit for each part by weight <strong>of</strong> acid), left over night without<br />
filtering, then collected again at the pump, washed with alcohol,<br />
and finally the almost colourless material is recrystallised from<br />
spirit, in which it is dissolved by boiling under reflux. The pure<br />
cholic acid separates on cooling in the form <strong>of</strong> transparent tetrahedral<br />
crystals. Melting point 196°. A further quantity <strong>of</strong> pure<br />
substance can be obtained from the mother liquor by concentration.<br />
If the acid, partially purified as described, is extracted in<br />
a thimble with ethyl acetate, a very fine preparation is obtained.<br />
The yield <strong>of</strong> pure acid amounts to fully 50 g.<br />
The methyl ester <strong>of</strong> the acid can very conveniently be prepared<br />
by esterifying in ten parts <strong>of</strong> methyl alcohol with hydrogen chloride.<br />
After boiling for quite a short time, the cold solution, saturated with<br />
hydrogen chloride, is poured into a large volume <strong>of</strong> dilute sodium<br />
carbonate solution, and the ester, which is precipitated in solid form,<br />
is dried and recrystallised from a little dilute methyl alcohol. Other<br />
compounds which may suitably be prepared are dehydrocholic acid,<br />
cholatrienic acid, and cholanic acid.<br />
Desoxycholic Acid, Fatty Acids, Cholesterol.—The first alcoholic<br />
filtrate obtained during the crystallisation <strong>of</strong> the cholic acid (see<br />
above) is made strongly alkaline to phenolphthalein paper with 2 Nsodium<br />
hydroxide solution and concentrated to a syrupy consistency<br />
in a porcelain basin on the water bath. The syrup is taken up in<br />
250 c.c. <strong>of</strong> water, transferred to a separating funnel, cooled, covered
414 DBSOXYCHOLIC ACID<br />
with 250 c.c. <strong>of</strong> ether, and shaken well. Then 2 iV-sulphuric acid is<br />
gradually added from a dropping funnel with swirling. From time to<br />
time the separating funnel is vigorously shaken in order to dissolve<br />
as much as possible <strong>of</strong> the precipitated acid in the ether. When the<br />
aqueous solution has become acid to Congo paper it is run <strong>of</strong>f from<br />
undissolved matter and the green ether layer is also poured <strong>of</strong>f.<br />
The resinous material is dissolved by shakjng with the necessary<br />
amount <strong>of</strong> dilute ammonia, and after 200 c.c. <strong>of</strong> fresh ether have been<br />
added the precipitation is repeated as before. Any resin which now<br />
remains is discarded. The combined ether extracts are at once<br />
shaken twice with 10 c.c. portions <strong>of</strong> hydrochloric acid (1 part <strong>of</strong><br />
concentrated acid, 2 parts <strong>of</strong> water) so that the pigment is precipitated<br />
as a green resin. The clear ethereal solution, which, however,<br />
always remains green, is now concentrated to 50 c.c. and left<br />
in the cold to allow the acid to crystallise. After twenty-four hours<br />
2-5-3-0 g. <strong>of</strong> desoxycholic add will have separated in the form <strong>of</strong> wellcrystallised<br />
" choleic " acid (see below). The crystals are collected<br />
at the pump, washed once with ether, and recrystallised directly<br />
from three volumes <strong>of</strong> glacial acetic acid. From the acetic acid<br />
solution, on cooling, the compound <strong>of</strong> desoxycholic acid with acetic<br />
acid (" acetic acid choleic acid ") separates in beautiful prisms which<br />
melt at 142°. In the simple manner here given only about onequarter<br />
to one-fifth <strong>of</strong> the total desoxycholic acid is obtained. The<br />
other methods <strong>of</strong> isolation are, however, very troublesome.<br />
In a small round-bottomed flask the ethereal mother liquor is<br />
concentrated to a volume <strong>of</strong> 10 c.c, 50 c.c. <strong>of</strong> low-boiling petrol<br />
ether are added, and the stoppered flask is shaken continuously until<br />
a clear solution is obtained. The petrol ether which is now poured<br />
out contains fatty acids and cholesterol, whereas the bile acids formerly<br />
in solution in the ether have separated as a thick resinous mass.<br />
In order to separate the fatty acids and the cholesterol the petrol<br />
ether solution is carefully shaken with 50 to 60 c.c. <strong>of</strong> 2iV-potassium<br />
hydroxide solution. This solution is added in 10 c.c. portions,<br />
and each portion is at once removed so as to avoid emulsions.<br />
The aqueous extracts containing the soaps are freed from<br />
dissolved petrol ether by heating in a beaker on the boiling water<br />
bath, and the fatty acids are then precipitated with hydrochloric<br />
acid; they set to a cake on cooling. The yield is 4-5 g.<br />
When the petrol ether solution from which the acids have been<br />
removed is evaporated to dryness 0-2-0-4 g. <strong>of</strong> cholesterol is left.
CHOLBSTBKOL 415<br />
From a little alcohol it crystallises beautifully in characteristic<br />
nacreous scales. Melting point 145°.<br />
The two most important bile acids, cholic acid C24H40Os and desoxycholic<br />
acid C24H40O4, occur in ox bile in combination, partly with glycine<br />
and partly with taurine as glyco- and taurocholic and glyco- and taurodesoxycholic<br />
acids. The linkage between the amino acids and the bile<br />
acids is <strong>of</strong> an amide nature. On hydrolysis the nitrogenous constituents<br />
are split <strong>of</strong>f.<br />
Cholanic acid C24H40O2, a monobasic saturated acid containing four<br />
hydroaromatic rings, is the parent substance <strong>of</strong> the two natural acids,<br />
which are its trihydroxy- and dihydroxy-derivatives. It is very highly<br />
probable that the following structural formula for cholic acid is correct:<br />
CH3<br />
I 3<br />
I<br />
H CH.CH2.CH2.CO2H<br />
OH<br />
Androsterone C19H30O2<br />
Cholesterol C27H45OH, an unsaturated secondary alcohol, contains<br />
the same ring system as the bile acids and is closely related to them<br />
genetically. Pseudocholestane, indeed, which is a stereoisomer <strong>of</strong> the<br />
parent hydrocarbon <strong>of</strong> cholesterol, cholestane, can be oxidised to cholanic<br />
acid by chromic acid with elimination <strong>of</strong> acetone (Windaus).<br />
CH3<br />
Pseudocholestane<br />
C23H39.COOH + O<br />
Cholanic acid
416 SOLVENT POWEK OF BILE ACIDS<br />
Conversely, pseudocholestane has also been obtained synthetically from<br />
cholanic acid.<br />
Ergosterol C^H^OH, a trebly unsaturated alcohol, is derived from<br />
the same ring system. It is produced in relatively large amounts by<br />
fungi, in particular by yeast, and on irradiation it is isomerised to the<br />
anti-rachitic vitamin, vitamin-D (Windaus).<br />
Recent investigations have shown that a series <strong>of</strong> other biologically<br />
important substances, such as the sex hormones (Butenandt, Doisy,<br />
Ruzicka, Slotta), the cardiac poisons <strong>of</strong> digitalis and strophanthus<br />
(Jacobs, Tschesche) and the toad poisons contain the same tetracyclic<br />
skeleton as do the bile acids and sterols. As a result <strong>of</strong> these researches<br />
a large new group <strong>of</strong> natural substances, appropriately named the sterol<br />
group, has been recognised. The structure <strong>of</strong> the male sex hormone,<br />
androsterone, is given above.<br />
The method for the dehydrogenation <strong>of</strong> hydroaromatic rings with<br />
selenium introduced by 0. Diels has rendered important service in these<br />
investigations.<br />
ChoUc acid, and still more desoxycholic acid, excel in their power <strong>of</strong><br />
combining in stoicheiometrical proportions with organic substances<br />
belonging to all kinds <strong>of</strong> chemical classes. Thus the " choleic " acid<br />
<strong>of</strong> bile, which was formerly regarded as an isomer <strong>of</strong> desoxycholic acid,<br />
is simply an addition compound <strong>of</strong> eight molecules <strong>of</strong> desoxycholic acid<br />
with one <strong>of</strong> a higher fatty acid. The high solvent power <strong>of</strong> solutions <strong>of</strong><br />
the alkali salts <strong>of</strong> desoxycholic acid (and cholic acid) is also connected<br />
with this property.<br />
Experiments—Dissolve 0-4 g. <strong>of</strong> the acetic acid-desoxycholic<br />
acid compound, prepared as above, in 4 c.c. <strong>of</strong> 2 i\f-sodium hydroxide.<br />
Prepare also from about 100 mg. <strong>of</strong> the fatty acids isolated, by boiling<br />
with a few cubic centimetres <strong>of</strong> dilute sodium hydroxide solution,<br />
a soap solution and cool it till it sets to a jelly. Add part <strong>of</strong> the<br />
solution <strong>of</strong> desoxycholic-acetic acid. The soap dissolves.<br />
In the same way dissolve a few granules <strong>of</strong> naphthalene in<br />
0-5 c.c. <strong>of</strong> alcohol, pour the solution into twice its volume <strong>of</strong> water,<br />
and at once (before large crystals form) add a few drops <strong>of</strong> the<br />
desoxycholic-acetic acid solution to the milky suspension <strong>of</strong> the<br />
hydrocarbon. A clear solution is produced.<br />
For further details see Z. physiol. Chem., 1916, 97, 1.<br />
Experiments—Dissolve 0-02 g. <strong>of</strong> cholic acid in 0-5 c.c. <strong>of</strong> alcohol<br />
and add to the solution 1 c.c. <strong>of</strong> 0-1 iV-iodine solution. On cautious<br />
dilution with water the blue crystalline iodine compound <strong>of</strong> cholic<br />
acid, comparable to " starch iodide," separates.<br />
Experiment.-—Barium Desoxycholate.—Dissolve a small sample
BAKIUM DBSOXYCHOLATB 417<br />
<strong>of</strong> desoxycholic acid in dilute ammonia to a clear solution and add<br />
barium chloride solution. The sparingly soluble barium salt is at<br />
once precipitated as a tough mass, which crystallises in beautiful<br />
rosettes when left over night. Distinction from cholic acid, the<br />
barium salt <strong>of</strong> which is more soluble in water.<br />
Experiments—Dissolve about 5 mg. <strong>of</strong> cholesterol in 1 c.c. <strong>of</strong><br />
acetic anhydride and add a drop <strong>of</strong> concentrated sulphuric acid. A<br />
magnificent play <strong>of</strong> colours is produced (Liebermann-Burchard<br />
cholestol reaction).<br />
2 E
HINTS FOE USING THE LITEKATUKB OF<br />
ORGANIC CHBMISTKY<br />
THE multitudinous compounds <strong>of</strong> carbon, over 200,000 in number,<br />
are so well arranged in chemical reference books that it is a simple<br />
matter to obtain particulars about any one <strong>of</strong> them. Students<br />
should know their way about the library quite early in their course,<br />
at the latest when they begin to prepare substances described in<br />
original papers. In order to supply this knowledge some directions<br />
are given here.<br />
The foundation-stone <strong>of</strong> the systematic arrangement <strong>of</strong> organic<br />
compounds is the'principle <strong>of</strong> the " formula index " which was first<br />
worked out by M. M. Kichter in his Formel-Lexikon der organischen<br />
Verbindungen, <strong>of</strong> which the third edition includes the material<br />
available up to the year 1910. The compounds are grouped, according<br />
to the number <strong>of</strong> carbon atoms in the molecule, in a numerical<br />
series from Cj upwards. In the separate groups those substances<br />
come first which contain only one element in addition to carbon, and<br />
they are so arranged that the additional elements follow each other<br />
in the order H, O, N, Halogen, S, P, As ; then come the compounds<br />
with two, three, and more elements besides carbon, arranged as<br />
before. For example, if information is wanted about methyl pchlorobenzoate<br />
a search is made in Richter's Lexikon in the volume<br />
which contains the compounds <strong>of</strong> the C8 series, since the substance<br />
has the molecular formula C8H7O2C1. The headings in the upper<br />
corners <strong>of</strong> the pages lead to the group 8 III, i.e. to the list <strong>of</strong> organic<br />
compounds which contain three other elements besides eight carbon<br />
atoms.<br />
Since the known compounds in the group C8III are arranged<br />
according to the number <strong>of</strong> atoms <strong>of</strong> the additional elements (H and<br />
0), it is easy to find the compound required.<br />
The Lexicon <strong>of</strong> the carbon compounds corresponds to the great<br />
reference work <strong>of</strong> Beilstein, which will be discussed later. Accordingly,<br />
for our compound the Lexicon gives, in addition to a brief<br />
419 2 E 2
420 LITBKATUKB OF ORGANIC CHEMISTKY<br />
statement <strong>of</strong> melting or boiling point, also the place in Beilstein<br />
where more detailed information is available. Since Kichter's work<br />
covers more ground than that <strong>of</strong> Beilstein, <strong>of</strong> which the third edition<br />
with supplementary volumes only includes the literature up to<br />
July 1, 1899, Richter gives references to the original literature for<br />
the material which was lacking in Beilstein.<br />
The five-volume work <strong>of</strong> Stelzner forms the continuation <strong>of</strong><br />
Richter's formula lexicon. It covers the literature up to the year<br />
1921 and is arranged on the same plan as Richter's, but gives in<br />
addition a brief description <strong>of</strong> the individual substances, their<br />
constants and reactions, after the fashion <strong>of</strong> Beilstein.<br />
The indexing <strong>of</strong> organic compounds described since 1922 has been<br />
taken over by the Chemisches Zentralblatt, which follows the system<br />
hitherto discussed. The collective indexes <strong>of</strong> this journal for 1922 to<br />
1924,1925 to 1929, and 1930 to 1934 continue the classifying work <strong>of</strong><br />
M. M. Richter. In these indexes the references are to the Zentralblatt<br />
itself. Bach year <strong>of</strong> the Zentralblatt, from 1925 onwards, contains<br />
a formula index covering the annual increment <strong>of</strong> literature abstracted<br />
in this comprehensively planned journal. These formula<br />
indexes are amalgamated every few years into a collective index and<br />
individually they constitute the reference works for the period which<br />
has elapsed since the appearance <strong>of</strong> the last collective index. Consequently,<br />
when it is desired to have complete information from the<br />
whole literature about an organic substance, the following works<br />
must be consulted at the present day :<br />
1. Richter's Lexikon.<br />
2. Stelzner, 1911-1921.<br />
3. Collective Indexes <strong>of</strong> the Chemisches Zentralblatt, volumes vi.,<br />
1922-1924, vii., 1925-1929, and viii., 1930-1934.<br />
4. Formula indexes to the Zentralblatt for the years 1935, etc.<br />
Conscientious study <strong>of</strong> the literature is indispensable to the<br />
organic chemist. After a little practice the trouble <strong>of</strong> looking up<br />
references becomes inconsiderable, and a thorough knowledge <strong>of</strong> the<br />
literature on any particular point is <strong>of</strong> quite extraordinary value.<br />
It may spare the worker the irritation <strong>of</strong> trying unsuitable preparative<br />
methods which he may be tempted to apply because he has<br />
neglected to look up a good one hidden in the literature. Likewise,<br />
the danger <strong>of</strong> rediscovering already known compounds can only be
BEILSTBIN 421<br />
obviated by a thorough search through the chain <strong>of</strong> indexes mentioned.<br />
The references which we obtain in a successful search are <strong>of</strong><br />
various kinds. The main work <strong>of</strong> "Richter ", as already mentioned,<br />
first refers us to Beilstein's Handbuch der organischen Chemie, which<br />
may now be briefly described. The third edition <strong>of</strong> this work, in<br />
four volumes and as many supplementary volumes, gives a brief<br />
description <strong>of</strong> all pure organic compounds prepared up to July 1,<br />
1899, with their physical constants, methods
422 LITBKATUEB OF OKGANIC CHBMISTKY<br />
suitable. Unfortunately, owing to the vast amount <strong>of</strong> subject<br />
matter, some <strong>of</strong> its parts are unpleasantly out <strong>of</strong> date.<br />
An excellent reference work for preparations <strong>of</strong> technical interest<br />
is provided by the ten volumes <strong>of</strong> F. Ullmann's Enzyhlopddie der<br />
technischen Chemie, arranged alphabetically.<br />
In the four volumes <strong>of</strong> Die Methoden der organischen Chemie <strong>of</strong><br />
Houben and Weyl, all the methods used in organic laboratories are<br />
systematically collected and described, whilst the comprehensive<br />
book by Hans Meyer, Analyse und Konstitutionsermittlung organischer<br />
Verbindungen, is more concerned with analytical requirements.<br />
PREPARATIONS FROM THE ORIGINAL LITERATURE<br />
As a conclusion to his preparative course the student should<br />
undertake several preparations, for which he has to look up the<br />
appropriate methods in scientific journals, instead <strong>of</strong> finding them<br />
worked out in minute detail in a manual <strong>of</strong> laboratory instruction.<br />
In so doing he will learn, with the aid <strong>of</strong> the directions given above,<br />
how to consult the literature, and how to make use <strong>of</strong> the chemical<br />
library ; most <strong>of</strong> all, however, these more difficult preparations will<br />
serve to test his capacity for laboratory work. When synthesising<br />
a compound in several stages it is absolutely essential to test and consolidate<br />
each separate stage by means <strong>of</strong> test-tube experiments before<br />
the whole <strong>of</strong> the substance is risked. Whoever fails to observe<br />
this rule will pay dearly for his neglect by loss <strong>of</strong> material and time.<br />
The choice <strong>of</strong> difficult preparations will <strong>of</strong>ten be regulated by the<br />
requirements and desiderata resulting from the scientific work <strong>of</strong> the<br />
institute ; that the interests <strong>of</strong> the person who carries out the preparation<br />
must take precedence in this matter need not be emphasised.<br />
The following short list <strong>of</strong> preparations has proved suitable for the<br />
reasons given :<br />
Pinacone, Pinacoline<br />
O-Methylhydroxylamine<br />
Allyl Alcohol<br />
Styrene<br />
Stilbene<br />
Phenacyl Bromide<br />
Diphenyl<br />
Ethylene Oxide<br />
Choline<br />
Dithioglycollic Acid<br />
Oxalyl Chloride<br />
Nitrourea<br />
Nitramide<br />
Ethyl Orth<strong>of</strong>ormate<br />
Pumaric Acid<br />
Glutaric Acid<br />
Adipic Acid<br />
Pimelic Acid<br />
Cyanamide<br />
/3-Phenylethyl Alcohol<br />
Pyruvic Acid<br />
Oxalylacetic Acid<br />
Dihydroxytartaric Acid<br />
Dihydroxymaleic Acid<br />
Acetonedicarboxylic<br />
Acid (ethyl ester)<br />
Muconio Acid
PKBPAKATIONS FKOM THE LITBKATUEB 423<br />
Cadaverine<br />
Triphenylamine<br />
Fulminuric Acid<br />
Ethyl Azodicarbozylate<br />
y-Dinitrobenzene<br />
Aldol<br />
Crotonio aldehyde<br />
Phenylacetaldehyde<br />
Benzildioxime<br />
Phenylalanine<br />
Methylcyclohexenone<br />
y-Diketocyclohexane<br />
Diacetyl<br />
Mesitylene<br />
Acetonylacetone<br />
Antipyrine<br />
Carbon Suboxide<br />
Coumarin<br />
Allocinnamio Acid<br />
Xanthone<br />
Acridine<br />
Anthranol<br />
Di-biphenylene-ethylene<br />
/3-Nitronaphthalene<br />
Diphenylketene<br />
Camphorquinone<br />
Violuric Acid<br />
Veronal<br />
Phenylnitramine<br />
m-Toluidine<br />
m-Nitrophenol<br />
y-Nitrophenylhydrazine<br />
Fuchsone<br />
Hexahydroxybenzene<br />
Inositol<br />
o-Benzoquinone<br />
Quinol<br />
Hydroxyquinol<br />
Tetraphenylxylylene<br />
Dimethylaminobenzaldehyde<br />
Phenanthraquinone<br />
Biphenylene-ethylene<br />
Diphenylhydrazine<br />
Triphenylhydrazine and<br />
Hexaphenyltetrazane<br />
Tolane<br />
Mercury Diphenyl<br />
Dimethylpyrone<br />
1 : 5-Dibromopentane<br />
Diphenylnitric Oxide<br />
Thioindigotin<br />
Thioindigo Scarlet<br />
Isatin (Sandmeyer's<br />
method)<br />
Thymolphthalein<br />
Sodium Triphenylmethyl<br />
Dimethylpyrrole<br />
Mellitic Acid<br />
Methyliminazole from<br />
glucose<br />
a- and /3-Methylglucosides<br />
ttt-Camphor from pinene<br />
Cystine<br />
Hydrolysis <strong>of</strong> protein (according<br />
to E. Fischer<br />
and Dakin)<br />
Dihydroxyphenylalanine<br />
Glutamic Acid<br />
Glycyglycine<br />
Adrenaline<br />
Mannose<br />
Diacetoneglucose<br />
Dulcitol from galactose<br />
Sylvane from furfural<br />
Guanine<br />
Xanthine<br />
Uric Acid (synthetic)<br />
Camphoric Acid<br />
Camphoronic Acid<br />
o-Esdragole from phenylallyl<br />
ether<br />
Ionone<br />
Vanillin from iso-eugenol<br />
Tartrazine<br />
Auramine<br />
Tetraphenyl Lead<br />
Boron Triphenyl<br />
Phorone<br />
Ninhydrin<br />
Ethyl Chloro-iminocarbonate<br />
Diphenyldiazomethane<br />
Phenylacetylene<br />
Piperidine<br />
Piperylene<br />
Ethyl Cyclopentanone<br />
Carboxylate<br />
Picrolonic Acid<br />
os-Diphenylethylene<br />
Amylene from acetone<br />
Xylose<br />
Glyoxal<br />
Furfuryl Alcohol and<br />
Cinnamyl Alcohol<br />
(Meerwein's method)<br />
Glutathione
TABLE FOR CALCULATIONS IN THE DETERMINATION OF NITROGEN BY DUMAS' METHOD<br />
DENSITY OF DRY NmiooBif<br />
Weight <strong>of</strong> 1 c.c. <strong>of</strong> nitrogen in milligrammes under pressures between 700 and 770 mm. at temperatures between 10° and 25°. Calculated<br />
on the assumption that, under standard conditions, 1 c.c. <strong>of</strong> nitrogen weighs 1-2507 mg. (Lord Bayleigh's determination).<br />
p<br />
700<br />
702<br />
704<br />
706<br />
708<br />
710<br />
712<br />
714<br />
716<br />
718<br />
720<br />
722<br />
724<br />
726<br />
728<br />
730<br />
732<br />
734<br />
736<br />
738<br />
10°<br />
1-111<br />
1-114<br />
1-118<br />
1-121<br />
1-124<br />
1-127<br />
1-130<br />
1-133<br />
1-137<br />
1-140<br />
1-143<br />
1-146<br />
1-149<br />
1-152<br />
1-156<br />
1-159<br />
1-162<br />
1-165<br />
1-168<br />
1-172<br />
11°<br />
1-107<br />
1-110<br />
1-114<br />
1-117<br />
1-120<br />
1-123<br />
1-126<br />
1-129<br />
1-133<br />
1136<br />
1-139<br />
1-142<br />
1-145<br />
1-148<br />
1-152<br />
1-155<br />
1-158<br />
1-161<br />
1-164<br />
1167<br />
12°<br />
1103<br />
1-107<br />
1-110<br />
1-113<br />
1-116<br />
1-119<br />
1-122<br />
1-125<br />
1129<br />
1132<br />
1-135<br />
1-138<br />
1141<br />
1-144<br />
1-148<br />
1-151<br />
1-154<br />
1-157<br />
1-160<br />
1163<br />
13°<br />
1-100<br />
1-103<br />
1-106<br />
1-109<br />
1-112<br />
1-115<br />
1-118<br />
1-121<br />
1-125<br />
1-128<br />
1-131<br />
1-134<br />
1-137<br />
1-140<br />
1143<br />
1-147<br />
1-150<br />
1-153<br />
1-156<br />
1159<br />
14°<br />
1-096<br />
1-099<br />
1-102<br />
1-105<br />
1-108<br />
1-111<br />
1-114<br />
1-118<br />
1-121<br />
1-124<br />
1-127<br />
1-130<br />
1-133<br />
1-136<br />
1-139<br />
1-143<br />
1-146<br />
1-149<br />
1-152<br />
1-155<br />
15°<br />
1-092<br />
1-095<br />
1-098<br />
1-101<br />
1-104<br />
1-107<br />
1-111<br />
1-114<br />
1-117<br />
1-120<br />
1-123<br />
1-126<br />
1-129<br />
1-132<br />
1-136<br />
1-139<br />
1-142<br />
1-145<br />
1-148<br />
1-151<br />
16°<br />
1-088<br />
1-091<br />
1-094<br />
1-097<br />
1-101<br />
1-104<br />
1-107<br />
1-110<br />
1-113<br />
1-116<br />
1-119<br />
1-122<br />
1-125<br />
1-128<br />
1-132<br />
1-135<br />
1-138<br />
1-141<br />
1-144<br />
1-147<br />
17°<br />
1-084<br />
1-087<br />
1091<br />
1-094<br />
1-097<br />
1-100<br />
1-103<br />
1-106<br />
1-109<br />
1-112<br />
1-115<br />
1-118<br />
1-121<br />
1-125<br />
1-128<br />
1131<br />
1-134<br />
1-137<br />
1-140<br />
1-143<br />
18°<br />
1-081<br />
1-084<br />
1-087<br />
1090<br />
1093<br />
1-096<br />
1-099<br />
1-102<br />
1-105<br />
1-108<br />
1-111<br />
1-115<br />
1-118<br />
1-121<br />
1-124<br />
1-127<br />
1130<br />
1133<br />
1-136<br />
1139<br />
19°<br />
1-077<br />
1-080<br />
1-083<br />
1086<br />
1-089<br />
1-092<br />
1-095<br />
1-098<br />
1-101<br />
1-105<br />
1-108<br />
1-111<br />
1-114<br />
1-117<br />
1-120<br />
1-123<br />
1-126<br />
1-129<br />
1-132<br />
1135<br />
20°<br />
1-073<br />
1-076<br />
1079<br />
1-082<br />
1-085<br />
1-089<br />
1-092<br />
1-095<br />
1-098<br />
1-101<br />
1-104<br />
1-107<br />
1-110<br />
1-113<br />
1-116<br />
1-119<br />
1-122<br />
1-125<br />
1-128<br />
1131<br />
21°<br />
1-070<br />
1-073<br />
1-076<br />
1-079<br />
1-082<br />
1-085<br />
1-088<br />
1-091<br />
1-094<br />
1-097<br />
1-100<br />
1-103<br />
1-106<br />
1-109<br />
1112<br />
1-115<br />
1-118<br />
1-121<br />
1-125<br />
1-128<br />
22°<br />
1-066<br />
1-069<br />
1-072<br />
1-075<br />
1-078<br />
1-081<br />
1084<br />
1-087<br />
1-090<br />
1-093<br />
1-096<br />
1-099<br />
1-102<br />
1-105<br />
1-109<br />
1-112<br />
1-115<br />
1-118<br />
1-121<br />
1-124<br />
23°<br />
1-062<br />
1-065<br />
1-068<br />
1-071<br />
1-074<br />
1-077<br />
1-081<br />
1-084<br />
1-087<br />
1090<br />
1-093<br />
1-096<br />
1-099<br />
1-102<br />
1-105<br />
1-108<br />
1-111<br />
1-114<br />
1-117<br />
1120<br />
24°<br />
1-059<br />
1-062<br />
1-065<br />
1-068<br />
1-071<br />
1-074<br />
1-077<br />
1-080<br />
1083<br />
1-086<br />
1-089<br />
1-092<br />
1-095<br />
1-098<br />
1-101<br />
1-104<br />
1-107<br />
1-110<br />
1-113<br />
1116<br />
25°<br />
1055<br />
1-058<br />
1-061<br />
1-064<br />
1-067<br />
1-070<br />
1-073<br />
1-076<br />
1-079<br />
1-082<br />
1-085<br />
1-088<br />
1-091<br />
1-094<br />
1-097<br />
1-100<br />
1-103<br />
1-106<br />
1-109<br />
1-112<br />
P<br />
700<br />
702<br />
704<br />
706<br />
708<br />
710<br />
712<br />
714<br />
716<br />
718<br />
720<br />
722<br />
724<br />
726<br />
728<br />
730<br />
732<br />
734<br />
736<br />
738<br />
H<br />
W<br />
U<br />
H<br />
H<br />
o
740<br />
742<br />
744<br />
746<br />
748<br />
750<br />
752<br />
754<br />
756<br />
758<br />
760<br />
762<br />
764<br />
766<br />
768<br />
770<br />
P<br />
f (mm.)<br />
1-175<br />
1-178<br />
1-181<br />
1-184<br />
1-187<br />
1-191<br />
1-194<br />
1-197<br />
1-200<br />
1-203<br />
1-206<br />
1-210<br />
1-213<br />
1-216<br />
1-219<br />
1-222<br />
10°<br />
5-6<br />
1-171<br />
1-174<br />
1-177<br />
1-180<br />
1-183<br />
1-186<br />
1190<br />
1-193<br />
1-196<br />
1-199<br />
1-202<br />
1-205<br />
1-209<br />
1-212<br />
1-215<br />
1-218<br />
11°<br />
6-0<br />
1-166<br />
1-170<br />
1-173<br />
1-176<br />
1-179<br />
1182<br />
1-186<br />
1-189<br />
1-192<br />
1-195<br />
1-198<br />
1-201<br />
1-204<br />
1-207<br />
1-211<br />
1-214<br />
12°<br />
6-4<br />
1-162<br />
1-165<br />
1-169<br />
1-172<br />
1-175<br />
1-178<br />
1-181<br />
1-185<br />
1-188<br />
1191<br />
1-194<br />
1-197<br />
1-200<br />
1-203<br />
1-206<br />
1-209<br />
13°<br />
6-9<br />
1-158<br />
1-161<br />
1-165<br />
1-168<br />
1-171<br />
1-174<br />
1-177<br />
1-180<br />
1-183<br />
1-186<br />
1-190<br />
1-193<br />
1196<br />
1199<br />
1-202<br />
1-205<br />
14°<br />
7-3<br />
1-154<br />
1-157<br />
1-160<br />
1-164<br />
1-167<br />
1-170<br />
1-173<br />
1-176<br />
1-179<br />
1-182<br />
1-185<br />
1-189<br />
1-192<br />
1-195<br />
1-198<br />
1-201<br />
15°<br />
7-8<br />
1-150<br />
1-153<br />
1-156<br />
1-160<br />
1-163<br />
1-166<br />
1-169<br />
1-172<br />
1-175<br />
1-178<br />
1-181<br />
1-184<br />
1-188<br />
1-191<br />
1194<br />
1-197<br />
16°<br />
8-4<br />
1-146<br />
1-149<br />
1-152<br />
1-156<br />
1-159<br />
1-162<br />
1-165<br />
1-168<br />
1-171<br />
1-174<br />
1-177<br />
1-180<br />
1-183<br />
1-187<br />
1-190<br />
1193<br />
17°<br />
8-9<br />
1-142<br />
1-145<br />
1-149<br />
1-152<br />
1-155<br />
1-158<br />
1-161<br />
1-164<br />
1-167<br />
1-170<br />
1-173<br />
1-176<br />
1-179<br />
1-182<br />
1-186<br />
1-189<br />
18°<br />
9-5<br />
1-138<br />
1-141<br />
1-145<br />
1-148<br />
1-151<br />
1-154<br />
1-157<br />
1-160<br />
1-163<br />
1-166<br />
1-169<br />
1-172<br />
1-175<br />
1-178<br />
1-181<br />
1-185<br />
19°<br />
10-1<br />
1-135<br />
1-138<br />
1-141<br />
1-144<br />
1-147<br />
1-150<br />
1-153<br />
1-156<br />
1-159<br />
1-162<br />
1-165<br />
1-168<br />
1-171<br />
1-174<br />
1-177<br />
1-181<br />
20°<br />
10-8<br />
1-131<br />
1-134<br />
1-137<br />
1-140<br />
1-143<br />
1-146<br />
1-149<br />
1-152<br />
1-155<br />
1-158<br />
1-161<br />
1-164<br />
1-167<br />
1-170<br />
1-173<br />
1-176<br />
21°<br />
11-4<br />
1-127<br />
1-130<br />
1-133<br />
1136<br />
1-139<br />
1-142<br />
1-145<br />
1-148<br />
1-151<br />
1-154<br />
1-157<br />
1-160<br />
1-163<br />
1-166<br />
1-169<br />
1-172<br />
22°<br />
12-2<br />
1-123<br />
1-126<br />
1-129<br />
1-132<br />
1-135<br />
1-138<br />
1-141<br />
1-144<br />
1-147<br />
1-150<br />
1-153<br />
1-156<br />
1-159<br />
1-162<br />
1-165<br />
1-169<br />
23°<br />
12-9<br />
1-119<br />
1-122<br />
1-125<br />
1-128<br />
1-131<br />
1134<br />
1-137<br />
1-140<br />
1143<br />
1-146<br />
1-149<br />
1-152<br />
1-156<br />
1-159<br />
1-162<br />
1-165<br />
24°<br />
13-7<br />
1-115<br />
1-118<br />
1-121<br />
1-124<br />
1-128<br />
1-131<br />
1-134<br />
1-137<br />
1-140<br />
1-143<br />
1-146<br />
1-149<br />
1-152<br />
1-155<br />
1-158<br />
1-161<br />
25°<br />
14-6<br />
740<br />
742<br />
744<br />
746<br />
748<br />
750<br />
752<br />
754<br />
756<br />
758<br />
760<br />
762<br />
764<br />
766<br />
768<br />
770<br />
P<br />
f (mm.)<br />
If the confining liquid is 30 per cent potassium hydroxide, solution, the pressure <strong>of</strong> water vapour over this solution at the<br />
temperature concerned (f mm., see above) must be subtracted from the observed barometric pressure after reduction to 0°.<br />
o<br />
"si<br />
I—I<br />
H<br />
O Q<br />
U<br />
H<br />
W<br />
O<br />
u
SUBJECT INDEX<br />
(The page numbers which refer to the experiments <strong>of</strong> the practical course are<br />
printed in heavy type.)<br />
Absolute ether 91<br />
Accidents, prevention <strong>of</strong>, 26, 30-31, 71,<br />
88-89, 91, 148, 153, 159-160<br />
Acetaldehyde 205, 209<br />
Acetala 140<br />
Acetamide 129<br />
Acetanilide 128<br />
Acetic acid 220<br />
Acetic anhydride 126<br />
Acetic fermentation 212<br />
Acetoacetic eater 251<br />
Acetoacetic ester synthesis, mechanism<br />
<strong>of</strong>, 257, 258, 260<br />
Acetobromoglucose 390<br />
Acetonitrile 137<br />
Acetophenone 338, 346<br />
Acetyl, determination <strong>of</strong>, 82<br />
Acetylacetone 252<br />
Acetyl chloride 121<br />
Acetylene 209, 211<br />
Acrolein 110, 368<br />
a-Acrose 218<br />
Acrylic acid 120<br />
Acyloin condensation 222<br />
Adipic aldehyde 384<br />
Adsorption indicators 73<br />
Aetioporphyrin 408<br />
Alanine 229<br />
Alcoholic fermentation 403<br />
Alcoholic potash 99<br />
Aldehyde ammonia 207-208, 215<br />
Aldehyde resin 219<br />
Aldehydes, properties and reactions <strong>of</strong>,<br />
210-220<br />
Aldol condensation 219<br />
Aldoxime-N-ether 178<br />
Alizarin 334<br />
Alizarin blue 368<br />
Alizarin bordeaux 335<br />
Alkaloids, precipitants for, 406<br />
Alkyl disulphid.es 202<br />
Alkylene dihalides 110<br />
427<br />
Alkylene oxides 111, 126<br />
Alkylidene-6is-acetoacetic ester 362<br />
AHocinnamic acid 234<br />
Allyl derivatives <strong>of</strong> phenols 245<br />
Aluminium chloride 342<br />
Amide chlorides 131<br />
Amines, primary (Mendius' reaction), 138<br />
Amino acids, syntheses, 276<br />
properties <strong>of</strong>, 276<br />
determination, 277<br />
2>-Aminoazobenzene 303<br />
o-Aminobenzaldehyde 172<br />
a-Aminocarboxylic acids, esters <strong>of</strong>, 270<br />
o-Aminocinnamic acid 172<br />
y-Aininodimethylaniline 317<br />
a-Aminoketones 270<br />
y-Aminophenol 176<br />
a-Aminopyridine 365<br />
Amygdalin 231<br />
Androsterone 415<br />
Angeli-Rimini test for aldehydes 214<br />
Anhydrous ether 91<br />
Anhydrous sodium acetate 127<br />
Aniline 165<br />
alkylation <strong>of</strong>, 168<br />
bleaching powder test for, 167<br />
Aniline black 311<br />
Anilinoquinol 310<br />
Anilinoquinone 311<br />
Anisaldehyde 223<br />
Anisidine 245<br />
Anisoin 223<br />
Anisole 244<br />
Anschiitz tube 7, 39<br />
Anschutz and Thiele's adapter 22<br />
Anthocyanins 268<br />
Anthracene 334<br />
Anthracene blue 335<br />
Anthragallol 352<br />
Anthranilic acid 371<br />
Anthranol 335<br />
Anthraquinol 335
428 INDEX<br />
Anthraquinone 334<br />
Anthrone 335<br />
Antipyrine 297<br />
Apparatus for beginners 90-91<br />
Apparatus with standard ground joints 2<br />
Araban 386<br />
Arabinose 386<br />
Arginine hydrochloride 404<br />
Arsanilic acid 293, 294<br />
Arsenobenzene 295<br />
/8-Arylacrylic acids 233<br />
Aryl disulphides 202<br />
Arylpropionic acids 233<br />
Ascorbic acid 400<br />
Atophan 368<br />
Atoxyl 295<br />
Autocatalysis 148<br />
Autoxidation <strong>of</strong> aldehydes 212<br />
Auxochromic groups 180, 304<br />
Avertin 222<br />
Azibenzil 227<br />
Azides 289<br />
Azobenzene 181, 184, 312<br />
Azo-components 305<br />
Azo-dyes, analysis <strong>of</strong>, 301<br />
Azomethane 275<br />
Azomethines 167, 181<br />
Azoxybenzene 182, 189<br />
Babo's air bath 17<br />
Baeyer's test 112<br />
Bakelite 220, 243<br />
Baking process 198<br />
Bart's reaction 293, 295<br />
Bases, tertiary, degradation with cyanogen<br />
bromide, 364<br />
Bathychromic effect 248, 314<br />
Beckmann rearrangement 344<br />
Beer's law 354<br />
Beilstein's test 45<br />
Benzacetoin 223<br />
Benzaldehyde 209<br />
Benzamide 130<br />
Benzanilide 344<br />
Benzaurin 328<br />
Benzene from aniline 285<br />
from phenylhydrazine 299<br />
Benzene hexachloride 106<br />
Benzene ring, substitution in, 106, 163,<br />
164, 173, 197-199, 237<br />
Benzenesulphinic acid 193, 201<br />
Benzene sulphohydroxamic acid 192<br />
Benzenesulphonamide 192<br />
Benzenesulphonic acid 191<br />
Benzenesulphonyl chloride 192<br />
Benzhydrazide 153<br />
Benzidine 186<br />
Benzidine dyes 302<br />
Benzidine rearrangement 187<br />
Benzil 222<br />
Benzil dioximes 346<br />
Benzil monoximes 346<br />
Benzil osazone 223<br />
Benzilic acid 225<br />
rearrangement 225<br />
Benzohydrol 337<br />
Benzoic acid 220<br />
Benzoic anhydride 126<br />
Benzoin 222<br />
Benzonitrile 292<br />
Benzophenone 227, 343<br />
Benzophenone oxime 344<br />
Benzopyranole 268<br />
Benz<strong>of</strong>Hchloride 102<br />
Benzoylacetone 253<br />
Benzoylacetylacetone 263<br />
Benzoylacetyl peroxide 213<br />
Benzoyl azide 153<br />
o-Benzoylbenzoic acid 351<br />
Benzoyl chloride 121<br />
Benzoyl, determination <strong>of</strong>, 82<br />
Benzoyl peroxide 125<br />
Benzyl alcohol 220<br />
Benzylamine 102<br />
Benzyl chloride 100<br />
Benzyl cyanide 137<br />
Benzylideneacetone 181<br />
Benzylideneaniline 167<br />
Benzylidene chloride 102<br />
Benzylidene phenylhydrazone 297-298<br />
Bindschedler's green 321<br />
Bioses, constitution <strong>of</strong>, 397-398<br />
Biphenyleneglycollic acid 225<br />
Bis-diazoacetic acid 279<br />
Bis-y-dimethylaminodiphenyl-nitrogen<br />
359<br />
Bismarck brown 172<br />
Bitter almond oil 211<br />
Bixin 233 -<br />
Boric acid, increasing its conductivity<br />
with sugars, 396<br />
Borneol 226<br />
Bredt's rule 226<br />
Bromination 106, 119, 257, 261<br />
Bromine titration <strong>of</strong> enols 261<br />
Bromobenzene 103<br />
/3-Bromopropionic acid 120<br />
Bromotoluenes (o-, m-, p) 293<br />
Biichner funnel 9, 10<br />
Butadiene 113, 306<br />
Butyric acid 255<br />
Caffeine 405<br />
Camphene 87, 226
Cannizzaro's reaction 220<br />
Carbimide 139<br />
Carbodiphenylimide 170<br />
Carbohydrates 395-400<br />
Carboligase 223<br />
Carbonium salts 330, 355<br />
Carbon suboxide 227<br />
Carbyl sulphate 197<br />
Cardiac poisons 416<br />
Caro's acid, oxidation with, 179<br />
Carotene 233<br />
Carotenoids 233<br />
Casein 391<br />
hydrolysis <strong>of</strong>, 392<br />
Catalytic hydrogenation 376-383, 385<br />
Catechin 268<br />
Cellobiose 395<br />
Centrifuge 14<br />
Cetyl iodide 98<br />
Chlorauric acid 406<br />
Chlorine, determination <strong>of</strong>, 69, 73, 103<br />
carriers 119<br />
Chloroacetic acid 118<br />
o-Chlorobenzoic acid 106<br />
Chloroiodoethylene 285<br />
Chlorophyll 410, 411<br />
Chloroplatinic acid 406<br />
Cholanic acid 413, 415<br />
Cholatrienic acid 413<br />
Choleic acid 414<br />
Cholesterol 415<br />
Cholic acid 412<br />
Choline 116<br />
Chromanol 268<br />
Chromatographic adsorption 14-15,<br />
410.411<br />
Chromophoric groups 304<br />
Cinnamic acid 232<br />
hydrogenation <strong>of</strong>, 234, 377-378<br />
Citral 220<br />
Claisen flask 20, 31<br />
Clemmensen'a method <strong>of</strong> reduction<br />
383<br />
" Cold finger " 7<br />
Collidine 362<br />
Collidine dicarboxylic acid, ethyl ester,<br />
360<br />
Collidine dicarboxylic acid, potassium<br />
salt <strong>of</strong>, 362<br />
Compressed gases 35-37<br />
Concentration <strong>of</strong> reactants 3<br />
Congo red 302<br />
Conjugated double bonds 106, 113, 242<br />
Cooling methods 2<br />
Coproporphyrin 408<br />
Cost <strong>of</strong> materials 94-95<br />
Coumarin 238<br />
INDEX 429<br />
Coupling <strong>of</strong> diazonium compounds<br />
305-308<br />
Crocetin 233<br />
Croconic acid 225<br />
Crotonaldehyde 219<br />
Crotonic acid 233<br />
Cryptopyrrole 407<br />
Cryptopyrrole carboxylic acid 408<br />
Crystallisation 4-12<br />
Crystal violet 328<br />
Cupferron 177<br />
Cuprous cyanide 291<br />
Curtius reaction 153<br />
Cyanidin 268<br />
Cyanogen bromide and cyclic bases 364<br />
Cyanohydrin synthesis 230<br />
Cyclobutane dicarboxylic acid, ester <strong>of</strong>,<br />
266<br />
Cycloheptatriene carboxylic acid, ester<br />
<strong>of</strong>, 281<br />
Cyclohexane 107, 381, 382<br />
Cyclohexanol 379<br />
Cyclo-octatetraene 114<br />
Cyclopentadiene 113<br />
Cyclopentanone carboxylic acid, ester<br />
<strong>of</strong>, 259<br />
Cyclopropane derivatives 280<br />
Cysteine 202<br />
Cystine 202<br />
Decalin 381<br />
Dehydracetic acid 252, 267<br />
Dehydrocholic acid 413<br />
Dehydrogenation with selenium 416<br />
Dehydroindigo 367<br />
Delphinidin 268<br />
Desmotropism 262<br />
Desoxycholic acid 413<br />
Deuteroporphyrin 409<br />
Diacetyl 224<br />
Diacetylsuccinic acid ester 267<br />
Diacyl oxides 128<br />
Dialkyl oxides 128<br />
Dianisidine 187<br />
y-Dianisylnitrogen 358<br />
Diazoaminobenzene 282, 303<br />
Diazobenzeneamide 289<br />
Diazobenzeneimide 289<br />
Diazo-components 305<br />
Diazo-compounds, aliphatic, 271<br />
aromatic, 281<br />
Diazohydroxide 288<br />
Diazomethane 271<br />
determination <strong>of</strong>, 273<br />
Diazonium hydroxide type 288<br />
Diazonium salt solution 281<br />
Diazophenol ether 307
430 INDEX<br />
Diazotates 288<br />
Diazotising 283<br />
Dibenzoylacetone 262<br />
Dibenzyl from benzil 383<br />
£>-Dibromobenzene 105<br />
6 : 6'-Dibromoindigo 372<br />
Dichlorohydrin 97<br />
1 : 5-Dichloropentane 365<br />
Diela' diene synthesis 113<br />
Diethyl benzylmalonate 255<br />
Diethyl ethylmalonate 254<br />
Diethyl malonate 254<br />
syntheses with, 264-266<br />
Dihydrocollidine dicarboxylate, ethyl,<br />
361<br />
Dihydromuconic acid 112, 364<br />
Dihydroquinoline 368<br />
2 : 4-Dihydroxyacetophenone 347<br />
Dihydroxyalkyl peroxides 111<br />
Dihydroxymethyl peroxide 205<br />
/3-Diketones, constitution <strong>of</strong>, 260-264<br />
Dimethylamine 316<br />
y-Dimethylaminoazobenzene 305<br />
Dimethylaniline 168<br />
Dimethylmethanedisulphonic acid 216<br />
Dimethylpyrone 267<br />
Dimroth's condenser 1<br />
Dimroth-van't H<strong>of</strong>f constants 261<br />
Dinitroanthraquinones 335<br />
m-Dinitrobenzene 162<br />
Dinitroethanes 111<br />
Dinitronaphthalenes 336<br />
2 : 4-Dinitro-a-naphtholsulphonic acid<br />
195, 404, 405, 406<br />
Diphenyl 99, 338<br />
Diphenylamine test for nitric acid 357<br />
Diphenyldiphenoquinonediimonium sulphate<br />
357<br />
as-Diphenylethylene 342<br />
Diphenylhydroxylamine 182, 341<br />
Diphenyliodonium iodide 284<br />
Diphenylketene 227<br />
Diphenylmethyl carbinol 342<br />
Diphenylnitrogen 358, 359<br />
Diphenylnitrogen oxide 182<br />
Diphenylnitrosamine 358<br />
Diphenylsulphone 191<br />
Diphenylurea 154<br />
Diphenylthiourea 169<br />
Dismutation <strong>of</strong> hydrazobenzene 185<br />
Distillation 15 £E.<br />
high vacuum, 26<br />
Dithiocarbamic acids, ammonium salts,<br />
169<br />
Doebner's violet 320<br />
Drying oils 151<br />
Drying " pistol "14<br />
Dulcine 246<br />
Dulcitol 399<br />
Dyes, theory <strong>of</strong>, 304<br />
Electrolytic separation <strong>of</strong> tin 317<br />
Elementary analysis 46 fi.<br />
Emeraldine 312<br />
Emulsin 397<br />
Enol reactions 253, 261<br />
Eosin 326<br />
ammonium salt <strong>of</strong>, 327<br />
sodium salt <strong>of</strong>, 327<br />
Equilibrium, chemical, 142-145<br />
Equipment for beginners 90<br />
Ergosterol 416<br />
Erlenmeyer's rule 257<br />
Erythritol 97<br />
Esterification, theory <strong>of</strong>, 142-145<br />
Ether, purification <strong>of</strong>, 91-92<br />
peroxides in, 92<br />
Ethyl acetate 141<br />
Ethyl acetoacetate 251<br />
Ethyl alcohol 401<br />
Ethyl benzene 99<br />
from acetophenone 383<br />
Ethyl benzoate 141<br />
Ethyl benzylmalonate 255<br />
Ethyl bromide 93<br />
Ethyl diazoacetate 277<br />
Ethyl hydraziacetate 279<br />
Ethyl iodide 95<br />
Ethyl malonate 254<br />
Ethylmalonic acid 255<br />
Ethyl nitrate 148<br />
Ethyl nitrite 147<br />
Ethyl orth<strong>of</strong>ormate 139, 140<br />
Ethylsulphuric acid 109, 110<br />
Ethylene 107<br />
Ethylene bromohydrin 96<br />
Ethylene chlorohydrin 110, 111<br />
Ethylene dibromide 107<br />
Ethylene iodohydrin 98<br />
Ethylene oxide 116<br />
Eugenole 364<br />
" Exhaustive methylation " 364<br />
Extraction 32-35<br />
Faraday's law <strong>of</strong> electrochemical equivalents<br />
317-318<br />
Fat, hydrolysis <strong>of</strong>, 149<br />
Fats, hardening <strong>of</strong>, 381<br />
Fatty acids, higher, 149, 414<br />
Fermentation, alcoholic, 403<br />
Filtration 8-11<br />
<strong>of</strong> small quantities 10<br />
Fittig's reaction 99<br />
Flavianic acid 195, 404, 405, 406
Fluorene 260<br />
Fluorescein 326<br />
Formaldehyde 203<br />
determination <strong>of</strong>, 204-205<br />
Formhydroxamic acid chloride 350-351<br />
Formiminoether 13D<br />
Formyl chloride 350<br />
Friedel-Crafts synthesis 342 ff.<br />
d-Fructose 396<br />
Fuchsine 330<br />
Fuchsine-sulphurous acid test for aldehydes<br />
214<br />
Fuchsone 332<br />
Fuchsonimine 331<br />
Fulminates 159-160<br />
Fulminic acid 149<br />
Furane 113<br />
Furane-a:a'-dicarboxylic acid 400<br />
Furanoses 396<br />
Furfural 386<br />
reactions <strong>of</strong>, 387-388<br />
Furoin 223, 387<br />
d-Galactose 393<br />
Gallein 333<br />
Gattermann-Koch aldehyde synthesis<br />
213<br />
Gentiobiose 398<br />
Geranic acid 342<br />
Glucal 399<br />
d-Glucosazone 298<br />
d-Glucose 388<br />
Glucosides 268, 397<br />
Glutaconic acid 387<br />
Glutamic acid 202, 392<br />
Glutathione 202<br />
Glyceraldehyde 212, 218<br />
Glycerol 97, 150, 396<br />
Glycine 415<br />
Glycine ester hydrochloride 275<br />
Glycocholic acid 415<br />
Glycol 114-116<br />
Glycol diacetate 114-115<br />
GlycolHc acid 221<br />
Glycollic aldehyde 218<br />
Glycylalanine 276<br />
Glyoxal111<br />
Glyoxylic acid 221<br />
Gooch crucible 77<br />
Grignard reaction 337-342<br />
Guaiacol 238<br />
Haematinic acid 408<br />
Haemin 407, 408<br />
Haemoglobin 407<br />
Haemopyrrole 407<br />
Haemopyrrole carboxylic acid 408<br />
INDEX 431<br />
Halochromism 355<br />
Halogen, determination <strong>of</strong>, 69, 73, 76<br />
Hantzsch's collidine synthesis 360-363<br />
Heart poisons 416<br />
Helianthine 300<br />
Hell-Volhard-Zelinsky process 120<br />
Hexabromocyclohexane 106<br />
Hexachlorocyclohexane 106<br />
Hexachloroplatinic acid 406<br />
Hexamethylenetetramine 215<br />
Hexaphenylethane 352<br />
High vacuum distillation 26<br />
Hippuric acid 233, 277<br />
Hoesch ketone synthesis 347<br />
H<strong>of</strong>mann degradation <strong>of</strong> tertiary bases<br />
364<br />
H<strong>of</strong>mann degradation <strong>of</strong> amides 152<br />
Holoquinonoid salts 320<br />
Homolka'a base 331<br />
Hydrazine 279<br />
Hydrazobenzene 183<br />
Hydrazodicarbonamide 134<br />
Hydrazyls 359<br />
a-Hydrindone 350<br />
Hydrobenzamide 215<br />
Hydrobromic acid 105, 390<br />
Hydrocinnamic acid 234, 377<br />
Hydrocyanic acid 139<br />
Hydr<strong>of</strong>errocyanic acid 406<br />
Hydrogen bromide 105, 390<br />
Hydrogen, determination <strong>of</strong> active, 84<br />
Hydrogen ion determination with ethyl<br />
diazoacetate 280<br />
Hydrogenation with nickel 379<br />
with palladium 376<br />
Hydrogen peroxide, spontaneous decomposition,<br />
185-186<br />
Hydroquinone, see Quinol<br />
Hydroxamic acids 215<br />
y-Hydroxyazobenzene 183<br />
y-Hydroxybenzaldehyde 236<br />
y-Hydroxybenzyl alcohol 243<br />
a-Hydroxyisopropylsulphonic acid 216<br />
4-Hydroxypyrazole 281<br />
/3-Hydroxypyridinium salts 387<br />
a-Hydroxysulphonic acids 216<br />
Hydroxythionaphthene 375<br />
Imide chlorides 131<br />
Iminoethers 139<br />
Indamines 312, 321<br />
Indanthrene 373<br />
Indigo 369<br />
vat 373<br />
white 374<br />
Indole 299<br />
Indolone 371
432 INDEX<br />
Inversion <strong>of</strong> cane sugar 388<br />
Invertase 388<br />
Iodine value 151<br />
Iodine, volumetric determination <strong>of</strong>, 76<br />
Iodobenzene 283<br />
Iodo compounds from chloro- and<br />
bromo- compounds 98<br />
Iodonium salts 285<br />
Iodoaobenzene 284<br />
Iodoxybenzene 284<br />
Isatin 375<br />
Isatinic acid 375<br />
Isoamyl ether 117<br />
Isoamyl mtnte 146<br />
Isodiazotates 288<br />
Isoeugenole 364<br />
Isomtramines 177<br />
Isomtnle reaction 152, 167<br />
Isonitnles 139<br />
Isonitroso-ethyl acetoacetate 308<br />
Isonitroso-compounds, 147, 259<br />
Isoprene 113<br />
Isopropyl iodide 97<br />
bromide 266<br />
Isovaleric acid 266<br />
Keratin 202<br />
Ketenes 128, 227<br />
/3-Ketocarboxyhc esters, constitution <strong>of</strong>,<br />
259<br />
Keto-enol tautomensm 257 fi.<br />
Ketonic hydrolysis 266<br />
Ketyls 354<br />
Kishner-Wolff method <strong>of</strong> reduction 384<br />
Knoevenagel ring closure 363<br />
Kojic acid 267<br />
Kolbe's reaction 249<br />
Lactose 391, 392, 393<br />
Laevoglucosan 398<br />
Laevulinic acid 266<br />
Lead dioxide 325<br />
assay <strong>of</strong>, 325<br />
Lead tetra-acetate 117, 227<br />
Leucine 392<br />
Leuco-base <strong>of</strong> malachite green 324<br />
Leuco-compounds 333<br />
Liebermann reaction 317, 417<br />
Linolenic acid 151<br />
Linolic acid 151<br />
Lithium, organic compounds <strong>of</strong>, 340<br />
Lipochromes 233<br />
Luteobn 268<br />
Lycopene 233<br />
Malachite green 325<br />
Maleic anhydride 113<br />
Malt extract 401<br />
Maltose 397<br />
Maltose, determination <strong>of</strong>, 401<br />
Mandehc acid 228<br />
Mandelonitrile 227<br />
Mannitol 97<br />
Mannose 399<br />
Martms' yellow 199<br />
Mass action law 143 fi.<br />
Meerwein's reaction 221, 222<br />
Melting point, determination <strong>of</strong>, 40<br />
Mercaptans 201<br />
Menquinonoid dyes 319<br />
Mesidine 168<br />
Metaldehyde 217, 218<br />
Methazonic acid 161<br />
Methoxyl, determination <strong>of</strong>, 80<br />
Methyl alcohol, isolation as y-nitrobenzoate<br />
124<br />
Methylamine 152, 155, 158, 271<br />
/}-Methylanthraqmnone 352<br />
Methylation <strong>of</strong> phenols 244<br />
y-Methylazobenzene 181<br />
Methyl bromide 95<br />
a-Methylbutadiene 364<br />
Methylene-blue 219, 322<br />
3 • 4-Methylethylpyrrole 408<br />
Methylglyoxal 384<br />
Methylheptenone 342<br />
Methylhydroxylamine 158<br />
a-Methylindole 299<br />
Methyl iodide 96<br />
Methylnitrolic acid 160<br />
Methyl orange 300<br />
|8-Methylpyrrolidine 364<br />
Methyl red 300<br />
Michler's ketone 328<br />
Millon's reagent 393<br />
Molecular compounds 319<br />
Molecular weight determination 86<br />
Monopersulphuric acid 179<br />
Mordants 335<br />
Mucic acid 393, 399<br />
Muconic acid 112<br />
Murexide reaction 136<br />
Mutarotation 389, 395<br />
Naphthalene-/3-3ulphonic acid 194<br />
Naphthazarin 336<br />
Naphthionic acid 199<br />
Naphthols 238, 242<br />
|8-Naphthol orange 303<br />
Naphthol yellow S 195, 404, 405, 406<br />
Naphthoquinones 313<br />
Naphthylamine 199, 240<br />
|8-Naphthyl benzoate 242<br />
/?-Naphthyl methyl ether 244
Nerolin 244<br />
New fuchsine 329<br />
Nickel catalyst 379<br />
Nicotine 406<br />
m-Nitraniline 171<br />
Nitranilines, basicity <strong>of</strong>, 173-174<br />
Nitric oxide 357<br />
Nitric oxide-potassium sulphite compound<br />
177<br />
Nitriles, use in the Houben-Hoesch<br />
ketone synthesis, 347<br />
Nitroacetic acid 161<br />
Nitroacetonitrile 161<br />
j8-Nitroalizarin 368<br />
o-Nitrobenzaldehyde 371<br />
Nitrobenzene 161<br />
mechanism <strong>of</strong> reduction <strong>of</strong>, 188-190<br />
y-Nitrobenzoyl chloride 124<br />
aei-Nitr<strong>of</strong>luorene 260<br />
Nitrogen determination 47 ; table, 424<br />
Nitrogen peroxide 111<br />
Nitrogen-phenyl 312<br />
Nitrolic acids 160<br />
Nitromethane 156<br />
Nitrones 178<br />
m-Nitrophenol 247<br />
o- and y-Nitrophenols 246<br />
y-Nitrophenylarsinic acid 393<br />
Nitrosamines 269, 315, 359<br />
Nitrosobenzene 179, 188<br />
from aniline 179<br />
Nitroso-compounds, properties <strong>of</strong>,<br />
180 fE.<br />
y-Nitrosodimethylaniline 314<br />
y-Nitrosodiphenylamine 315<br />
Nitrosoisobutane 180<br />
Nitrosomethylurea 271<br />
Nitrosomethylurethane 274<br />
y-Nitrosophenol 316<br />
Nitrosophenylhydroxylamine 177<br />
m-Nitrotoluene 286<br />
o-Nitrotoluene 371<br />
Nitrous acid, preparation <strong>of</strong>, 357<br />
Nitroxyl 193, 214, 215<br />
Norcaradiene carboxylic ester 281<br />
Octa-acetylcellobiose 394<br />
Olefines 110<br />
Ornithine 277<br />
Ornithuric acid 277<br />
Osazones 223-224, 298<br />
Osones 298<br />
Oxanthrone 335<br />
Oximes, stereoiaomerio, 344-346<br />
Oxonium salts 267<br />
Ozonides 385<br />
Ozonisation 384<br />
INDEX 433<br />
Palladium on charcoal 378<br />
Paraformaldehyde 216<br />
Parafuchsine 329<br />
Paraldehyde 217<br />
Para red 288<br />
Partial valency 114<br />
Partition coefficient 32, 33<br />
Pelargonidin 268<br />
Peligot tube 104<br />
Penta-acetyl glucose 390<br />
Pentosans 386<br />
Peracetic acid 212<br />
Perbenzoic acid 111, 126, 151<br />
Perchloric acid 406<br />
Perkin's synthesis 232<br />
Persulphuric acid 179<br />
Pfungst tube 38<br />
Phenacetin 246<br />
Phenanthraquinone 225<br />
Phenetidine 245<br />
Phenol ethers 245<br />
Phenol from aniline 282<br />
Phenolphthalein 332<br />
Phenols, properties <strong>of</strong>, 240, 241<br />
Phenolsulphonic acids 199<br />
Phenylacetaldehyde 220<br />
Phenylacetaldoxime 178<br />
Phenylacetamide 141<br />
Phenylacetic acid 140<br />
Phenylacetic ester 281<br />
Phenylacetone 339<br />
Phenyl azide 289, 299<br />
Phenyl benzoate 241<br />
Phenyl cyanate 133, 153, 171<br />
Phenyldiazonium chloride, solid, 286<br />
Phenyldiazonium nitrate 287<br />
Phenyldiazonium perbromide 289<br />
Phenyldiimine 286<br />
Phenyl disulphide 202<br />
ro-Phenylenediamine 172<br />
Phenylglycine 369<br />
Phenylglycine-o-carboxylic acid 372<br />
Phenylhydrazine 223-224, 296, 298<br />
Phenylhydroxylamine 174, 176, 177<br />
Phenyliodochloride 284<br />
Phenylisothiocyanate 169, 171<br />
Phenyl magnesium bromide 337, 338<br />
Phenylnitroethylene 160, 178<br />
Phenylnitromethane 256<br />
Phenylquinonediimine 312<br />
Phenylsulphaminic acid 186, 198<br />
Phenyl sulphur chloride 202<br />
Phenyltriazene 289<br />
Phenylure thane 154<br />
Phloxin 333<br />
Phosphoric esters 98<br />
Phosphorus halides 97-98
434 INDEX<br />
Phosphotungstic acid 406<br />
Phthaleins 331<br />
Phthakdeins 333<br />
Phthalophenone 349<br />
Phyllopyrrole 407<br />
Phyllopyrrole carboxyho acid 408<br />
Physahen 233<br />
Phytol 410<br />
Picric acid 199, 247, 406<br />
Picryl chloride 249<br />
Punekc acid 250<br />
Pinacoline 225<br />
Pinacoline rearrangement 225<br />
Pinacolyl acohol 226<br />
Pinacone 225<br />
Pnie wood reaction 299, 394<br />
Pipendine 364<br />
Piperonal 220<br />
Piperylene 364<br />
Platinum oxide 379<br />
Polyenes 233<br />
Polymerisation 216<br />
Porphynns 408<br />
Potassium-benzil radicle 224<br />
Potassium cyanate 131<br />
Prileschaiev's reaction 111,.126, 151<br />
Propionamide 130<br />
Propionic acid 130<br />
Protoporphynn 409<br />
Pseudocholestane 415<br />
Pseudonitrols 158<br />
Pseudonitrosites 111<br />
Pseudophenyl&cetic ester 281<br />
PurpurogaHui 225<br />
Pyrainidone 297<br />
Pyranoses 396<br />
Pyrazoline tricarboxyhc esters 280<br />
Pyromucic acid 400<br />
Pyrones 267<br />
Pyroxonium salts 268<br />
Pyrrole 393, 394<br />
Pyrroles from haemin 407<br />
Pyruvic acid 110, 212, 403<br />
Quercetin 268<br />
Quinaldine 367<br />
Quinhydrone 314<br />
Quuiitol, stereoisomerism <strong>of</strong>, 107<br />
Quinizarin 335, 348<br />
Quinol 177, 212, 311<br />
Quinolimine 177<br />
Quinoline 366<br />
Quinone 113, 176,212,309<br />
determination <strong>of</strong>, 313<br />
Quinonedumines 319<br />
Quinone monoxime 316<br />
Quinophthalone 369<br />
Quinoxahne 224<br />
R acid 302<br />
Radicles, organic, 352<br />
Rast's method 86<br />
Reductive splitting <strong>of</strong> azo-dyes 301<br />
Reimer-Tiemann synthesis 235<br />
Reinecke's acid 406<br />
Resacetophenone 347<br />
Resolution <strong>of</strong> mandelic acid 228<br />
Retropinacoline rearrangement 226<br />
Rhodamines 333<br />
Rose bengale 333<br />
Runge's reaction 167<br />
Saccharase 388<br />
Saccharin 200, 201<br />
Sahcin 251<br />
Sahcylaldehyde 235<br />
Salicylic acid 250<br />
Salicylic acid by Kolbe's method 249<br />
Sahgenin 251<br />
Salol 251<br />
Salvarsan 295<br />
Sandmeyer's reaction 293<br />
Saponification value 151<br />
" Sausage " flask 17<br />
Schardinger's reaction 219<br />
Schiff's bases 167, 181<br />
Schmidlin's experiment 352, 353<br />
Schotten-Baumann reaction 124<br />
Schott's niters 69<br />
.Sealed tubes 69-71<br />
Selenium 416<br />
Selenium dioxide 384<br />
Semicarbazide 134<br />
Semidine transformation 187<br />
Silver fulminate 159<br />
Skraup's quinoline synthesis 366-368<br />
Soap 149, 150, 416<br />
Sodium acetate, anhydrous, 127<br />
Sodium amalgam 234<br />
Sodium azide 147<br />
Sodium hydroxide fusion 239<br />
Sodium y-mtrophenyl-amh-diazolate 290<br />
Sodium ac»-phenylnitroacetonitrile 256<br />
Sodium ac«-phenylnitromethane 256<br />
Sodium triphenylmethyl 353<br />
" Solid methylated spirits "218<br />
Starch, saocharification <strong>of</strong>, 401<br />
Steam distillation 27<br />
Steam distillation under reduced pressure<br />
278<br />
Sterols 416<br />
Stilbenediol, potassium derivative <strong>of</strong>,<br />
224<br />
Stirrers 39
Sublimation 26, 27<br />
Substitution, rules for, in benzene ring,<br />
164<br />
Succinio acid 267<br />
Succinylsuccmic acid, esters, 259<br />
Sucrose, inversion <strong>of</strong>, 388<br />
Sulphaminic acid 198<br />
Sulphinic acids 201<br />
Sulphonal 200<br />
Sulphonamides 200<br />
Sulphonation 191 fi.<br />
Sulphones 200<br />
Sulphonyl chlorides 200<br />
Sulphoxylates 220<br />
Sulphur, determniation <strong>of</strong>, 77, 78, 79<br />
Taunne 415<br />
Taurochohc acid 415<br />
Tautomerism <strong>of</strong> aldehydes and ketones<br />
257 fi.<br />
<strong>of</strong> aliphatic nitro-compounds 263<br />
Teichmann crystals 407<br />
Terephthalic acid 292<br />
y-Tetra-anisylhydrazine 358<br />
Tetrahydrophthahc acid 113<br />
Tetralin 381<br />
Tetramethylethylene 226<br />
Tetraphenylethylene 112<br />
Tetraphenylhydrazine 355, 358<br />
Tetrazanes 359<br />
Theobromme 405<br />
Thiele's theory 113<br />
Thioamides 139, 141<br />
Thioacetamide 139<br />
Thiocarbanilide 169<br />
Thionidigo 372<br />
Thioindigo scarlet 375<br />
Thionyl chloride 97<br />
Thiophenol 201<br />
Thiosahcyhc acid 372<br />
Tin, electrolytic separation <strong>of</strong>, 317<br />
granulation <strong>of</strong>, 165<br />
Toad poisons 416<br />
Tohdine 187<br />
Toluene-f>-sulphomc acid 193<br />
^-Toluic acid 292<br />
y-Tolunitrile 291<br />
y-Tolylaldehyde 350<br />
y-Tolylhydroxylamine 176, 177<br />
Trans-esterification 115<br />
Tnazenes 290<br />
Triazolone derivatives 290<br />
INDEX 435<br />
Tribromoethyl alcohol 222<br />
Tribromophenol 242, 243<br />
Tnbromophenol bromide 243<br />
Tridiphenylmethyl 354<br />
Triketopentane 181<br />
Trimethylamnie 116, 272<br />
Trinitrobenzene 164<br />
Triphenylcarbniol 338<br />
Triphenylchloromethane 346, 352, 353<br />
Triphenylguanidnie 170<br />
Tnphenylmethane 351, 353<br />
Triphenylmethane dyes, theoretical considerations,<br />
327<br />
Triphenylmethyl 352<br />
Tnphenylmethyl peroxide 353<br />
Turkey red 335<br />
Tyrian purple 372<br />
Z-Tyrosine 392<br />
Urea 132, 135<br />
Urethanes 134<br />
Uric acid 135<br />
Uroporphyrin 408<br />
Urotropine 215<br />
Vacuum desiccators 12, 13<br />
Vacuum distillation 23-26, 30-31<br />
Vanillin 211, 220, 238<br />
Vat dyes 373<br />
Vesuvine 172<br />
Vinyl bromide 106<br />
Vitamin-4 233<br />
Vitamin- O 400<br />
Vitamin-2? 416<br />
Volmer pump 26<br />
Witt filter plate 10<br />
Wohler's synthesis 133<br />
Wurster's red 319<br />
Wurtz synthesis 99<br />
Xanthophyll 233, 411<br />
Xylan 386<br />
f>-Xyloqurnone 224<br />
Z-Xylose 386<br />
Zeaxanthin 233<br />
Zeisel's method 80<br />
Zerevitin<strong>of</strong>Ts method 84<br />
Zinc amalgam 383<br />
Zinc alkyls 340<br />
Pjmieti m Great Britain by K & K Cl ARK, T IMUED, Edinburg,