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No. 68 FRIDAY, JANUARY 3, 1873.



SYNTHESIS OF AROMATIC MONAMINES BY | phenylamine or dimethyl toluidine; this, in a second INTRAMOLECULAR ATOMIC INTERCHANGE.*

By A. W. HOFMANN, M.D., LL.D., F.R.S.

phase of the reaction, becomes iodhydrate of monomethylated dimethylophenylamine or xylidine, which in its turn is ultimately converted into iodhydrate of trimethylophenylamine, i.c., of cumidine. The essential character of the reaction is thus seen to be an intermolecular change in the position of the methyl groups. According to the duration of the process, there are incorporated in the benzol nucleus, first the methyl group of the alcohol iodide, and then successively the two methylic groups which are stationed in the ammonia fragments. The action of heat on the quartary ammonium compound thus places at our disposal a simple means of rising from the benzol series itself to the toluol-, xylol, and cumol series, or, generally (for the reaction may probably be utilised in many other cases), of passing from a less carbonated to a more carbonated series of compounds.


In a paper submitted to the German Chemical Society about a year ago, we proved (Dr. Martius and myself) that the action of methylic alcohol on aniline chlorhydrate at a high temperature and under pressure, far from yielding exclusively methyl- and dimethylaniline, as has been formerly believed, is capable of causing methylation of the phenyl group, and thus producing quite a series of higher homologues of dimethylaniline.

If we endeavour to gain an insight into the mechanism of this reaction, we are led to assume that in the first instance the chlorhydric acid of the aniline salt gives rise to the formation of methylic chloride, which in its turn induces substitution, first in the ammonia fragment, and ultimately in the phenyl group itself. If, on the other hand, we remember that a tertiary monamine, such as must be formed by the final methylation of the ammonia frag

ment in aniline when submitted to the action of an alcohol chloride, is invariably converted into


ammonium compound, it must appear rather strange that in the process above alluded to only tertiary, and never any quartary bases are observed.

Under these circumstances the idea very naturally suggested itself of submitting the behaviour of quartary compounds at a high temperature under pressure to an experimental investigation.

The simplest compound that could be detected for such an inquiry appeared to be trimethylphenylammonium iodide, C6H5.CH3.CH3.CH3NI.

Reserving for a future communication the experimental details of this inquiry, I will limit myself for the present to a brief statement of the principal result obtained.

Leaving secondary reactions out of consideration, the transformation of the trimethylated phenylammonium iodide is represented by the following equations :

Transformation of quartary into tertiary compound. C6H5.CH3.CH3.CH3.NI=(C6H4.CH3)CH3.CH3N.HI. Transformation of tertiary into secondary compound. (C6H4.CH3)CH3.CH3.N.HI=

= C6H3(CH3(CH3)2] CH3.HN.HI.

Transformation of secondary into primary compound. [C6H3(CH3)2] CH3.HN.HI= [C6H2(CH3)3] HHN.HI. Accordingly trimethylated phenylammonium iodide, when submitted to the action of heat, is transformed in the first place into iodhydrate of dimethylated methylo


* A paper read before the Royal Society.
↑ Hofmann and Martius, Bericht, 1871, p. 742.

In carrying out the researches, the general results of which are sketched in the preceding paragraphs, rather considerable quantities of trimethylated phenylammonium iodide were consumed. This I obtained partly by methylating pure aniline with methyl iodine, partly by starting from commercial dimethylaniline, which was most liberally supplied to me by my friends Dr. D. Martius and Mendelssohn Bartholdy, having been specially purified for this purpose by Mr. G. Krell, by fractional distillation in the laboratory of the factory. This purified material was found to boil between 192° and 200°; and only few rectifications were necessary in order to obtain from it dimethyaniline in a state of perfect purity, identical in every respect with the base prepared distillation. Pure dimethylaniline is a liquid of o9553 by submitting trimethylated phenylammonium hydrate to V.W., solidifying to a crystalline mass at +0.5°, and boiling at 192°. The boiling-point was repeatedly determined, since it had been erroneously stated by M. Louth* to be 202°. The nature of the compound was ascertained by the analysis of the beautiful platinum-salt 2[C6H5(CH3)2N.HCI].PtC14, crystallising in well-formed tables of considerable solubility.

In the early experiments trimethylated phenylammonium iodide was employed in the pure state, such as is obtained by crystallisation; subsequently, however, it was found to be quite sufficient if I mol. of dimethylaniline was mixed with 1 mol. of methyl iodide, and the compound thus produced at once submitted to the action of heat.

The quartary iodides may be exposed to a temperature of 200 for a considerable time without undergoing any alteration; but when heated for a day to from 220° to 230°, the salt is changed, the whole crystalline compound

*Louth, Bull. Soc. Chim. (2) vol. vii., page 448.

being transformed into an amber-yellow viscid mass, | quartary iodides; but, together with these compounds, exhibiting no longer a trace of crystalline structure. If there is formed a tertiary iodhydrate, the base of which the temperature be then raised to the melting-point of is readily separated by distillation of the product with an lead (335) a further change is manifested by the amor- alkali. The base thus liberated has the V.W. o'9293, and phous resinous substances having solidified again to a boils at 196. Analyses of the platinum-salt proved it to hard mass of large radiated, generally rather coloured be dimethylated xylidine, crystals. On opening the digestion-tubes, appreciable quantities of uninflammable gas are evolved.


The products formed at moderate and temperatures essentially differ from one another. This is seen at once when the iodhydrates produced in both cases are decomposed by alkali, and the bases thus liberated are submitted to distillation in a current of steam. The

volatility of these bases shows the absence of quartary compounds; but whilst the monamines formed at moderate temperatures unite with acids to an extremely soluble salt, which are scarcely to be crystallised, those which are produced at high temperatures are found to solidify to rather difficultly soluble (readily crystallisable) salts with acids. The former bases exhibit the characters of tertiary and secondary, the latter ones those of primary monamines. Under these circumstances, it appeared desirable separately to examine the products formed in different conditions of temperature.

On submitting the iodhydrates formed at 220°-230° to distillation with alkali, a basic oil is obtained, which, when rectified after drying over hydrate of potassium, boils between 200 and 280°. By repeated distillation, the boiling-point is considerably lowered, small quantities of substances boiling beyond the range of the thermometer being separated. Finally, by far the greater portion of the bases is found to pass between 186 and 220°. This liquid consists of two varieties of dimethyltoluidine, of methylxylidine, and small quantities of dimethylxylidine. Of the two dimethyltoluidines, the one has the V.W. 09324, and boils constantly at 186°: the other has the V.W. o'9368, and boils at 205°, i.e. 19° higher than the former one. The nature of these two bases was fixed by the analysis of their platinum-salts,

2[C6H4.CH3) (CH3)2N.HCI].PtC14,

and also of the quartary iodide, (C6H4.CH3) (CH3)3NI, into which they were converted by the action of methyl iodides, and the platinum-salts corresponding to these iodide, 2[(C6H4.CH3) (CH3)3NCI].PtC14. The two dimethylated toluidines here described obviously correspond to two of the three modifications of toluidine, and very probably to the two liquid modifications. Dimethyltoluidine, obtained by converting solid toluidine into the trimethylated toluyl ammonium iodide, and then submitting the corresponding hydrate to distillation, has a V.W. o'988, and boils at 210°. The substance thus obtained, the composition of which was also established by analyses of the platinum-salt, essentially differs from the isomeric base boiling at 186°; it is less easily distinguished from the base boiling at 205°, with which more particularly it much agrees in odour; in fact these two compounds exhibit only the slight difference of 5o in their boiling-point. Still I believe them to be isomeric, not identical.

The presence of methylxylidine being only indirectly proved by analysis of the dimethylated base, it appeared desirable to establish the nature of the latter by addimine was converted, by means of methyl iodide, into the tional experiments. For this purpose the tertiary monaquartary compound, the characters of which could not be mistaken, its composition being, moreover, established by analysis of the beautiful platinum-salts.

2 [C6H3(CH3)2)] (CH3)3NCI] .PtC14.

In performing these experiments I was astonished to observe how difficultly dimethylxylidine combined with methyl iodide. Digestion at 100° produced no effect, and only heating the mixture for many hours to a temperaExamination of the Monamines formed at moderately ture of 150° combination took place, but even then only High Temperatures. to a very small extent.

It was this indifference of dimethylxylidine towards methyl iodide which enabled me to discover that small quantities of this compound are always formed, together with the monomethylated xylidine, when trimethylated phenylammoninm iodide is submitted to the action of heat. On treating the liquid, chiefly consisting of the two dimethylated toluidines and of monomethylated xylidine, with methyl iodide, these bases, as I have pointed out, are converted into iodine compounds; the small quantity of dimethylxylidine, which as such exists in the liquid, remains behind with the excess of methylic iodide, from which it may easily be separated by means of hydrochloric acid.

It deserves to be noticed that while the boiling-point of solid toluidine (202°), by the introduction of two methyl groups, is raised by 8°, the boiling temperature of one of the liquid modifications (198) is lowered by not less than Phenomena of this kind have been observed repeatedly in the course of this inquiry.


It was mentioned already that, in addition to the two dimethylated toluidines, the products of the action of heat on trimethylated phenylammonium iodide contains methylxylidine. I have not been able to isolate this compound; but it was not difficult to prove its presence by the action of methyl iodide on the mixed bases. The two dimethylated toluidines are thus converted into

C10H15N [C6H3(CH3)2] (CH3)2N,

which previous to methylation must have obviously
existed in the form of monomethylated xylidine,
C9H13N. [C6H3(CH3)2] CH3.HN.

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The formation of dimethylated toluidines and of monomethylated xylidine, requires no special explanation; it is due to intramolecular atomic interchange.

C6H5(CH3)3NI (C6H4. CH3) (CH3)2 N.HI. = [C6H4 · (CH3)2] CH3HN.HI.

For the generation of dimethylxylidine it is necessary to supply a methyl group from without. I have, however, already pointed out that, along with the principal transformation, several secondary reactions are taking place; those I hope to examine more minutely by-and-bye. Dimethylxylidine, which occurs in comparatively small quantity, obviously belongs to such a secondary change. The complementary product is probably monomethyltoluidine,

[C6H5(CH3)3NI] = (C6H4.CH3)CH3HN.HI, +[C6H4.(CH3)2] (CH3)2N.HI, which I have not, however, as yet been able to trace.

Whilst engaged with these experiments, I have, for the sake of comparison, converted a specimen of xylidine obtained from aniline-oil of high boiling-point into dimethylxylidine. The xylidine employed had constant boiling at 216°. The tertiary base procured from it was observed to boil at 203°, i.e., 7° higher than the compound derived from trimethylated phenylammonium iodide; from this last derivative it differed, moreover, by combining much more readily with methyl iodide. The quartary compound thus formed often remains liquid for days, and then suddenly solidifies into a beautiful mass of crystals.

Examination of the Monamines formed at High

It has been already stated that the bases into which trimethylated phenylammonium iodide is converted at

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New Method for Producing Amides and Nitriles.

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very high temperatures (melting-point of lead), unmistakably exhibit the character of primary monamines. The only primary base which can arise from trimethylated phenylammonium iodide by intramolecular atomic interch ange is a trimethylophenylated monamine, i.e., a cumidine, C6H5(CH3)3NI= [C6H2(CH3)3]H2N.HI. This, I may at once observe, is indeed the principal product of the reaction. It cannot, however, be wondered at that, under the influence of such extreme temperatures, many collateral changes must take place. The presence of dye-products is at once perceived, when the crystalline contents of the digestion tubes are submitted to distillation in a current of steam. Together with the vapour of water, a colourless oil is volatilised, consisting of hydrocarbons partly solid, partly liquid, the examination of which will form the subject of a future communication. Addition of an alkali to the liquid in the retort liberates considerable quantities of monamines, which, when dried over iodiamhydrate, are observed to boil between 225° and 260°. By repeated distillation this range of boiling is still considerably expanded; at the same time, by far the largest portion of the liquid is found to pass between 217 and 230°. The primary nature of this main fraction not only, but also of the bases, having both a lower and higher boiling-point, is at once manifested by the crystallising power and insolubility of the salts which they produce. At whatever stage of the distillation a drop of the liquid passing be mixed with dilute hydrochloric or nitric acid (invariably splendid), needles of chorhydrate or nitrates are formed, the solutions of which, even when considerably diluted, solidify with platinum perchloride double salts generally well crystallised. Another experiment rapidly indicating the primary character of these monamines may here be mentioned. On adding benzoyl chloride to the several basic fractions, much heat is evolved, and after cooling crystalline masses are produced, which are separated by water into soluble chlorhydrates and insoluble benzol compounds remaining behind, which may be crystallised from alcohol. None of the many secondary and tertiary monamines which have passed through my hands in the course of this inquiry exhibit this deportment, and accordingly benzoyl chloride may be recommended as a valuable reagent, readily applicable for primary bases. The method of recognising primary monamines which I have pointed out some time ago, and which consists in converting them, by means of alcoholic potash and chloroform, into the powerfully smelling isonitrites, may also with advan

tage be resorted to.

The liquid boiling between 217° and 230° was separated by distillation into four fractions, each of which was then converted into a magnificently crystalline chlorhydrate. These several salts, after re-crystallisation, were all found to contain [C6H2(CH3)3]H2N.HCl, and to yield platinum-salt of the composition


Taking into consideration the general observations recorded in the preceding paragraphs, the compound here designated as cumidine was naturally assumed to be a primary monamine. Little doubt as this conception appeared to present, it had nevertheless to be proved by experiment; for this purpose the base was submitted to methylation. Cumidine is readily acted upon by methylic iodide at the common temperature. Since it was only necessary to establish the degree of substitution the first product of methylation was at once submitted to a second treatment; this second methylation likewise commenced at the common temperature, but had to be finished in the water-bath. The dimethylated base thus obtained has the V.W. 09076; it boiled between 213° and 214°; hence, in this case also, the insertion of two methyl groups had lowered the boiling-point. Dimethyl cumidine may be cooled to -10° without solidifying; like all tertiary monamines, it forms very soluble salts, but gives a very beautiful platinum salt, containing

trace of red colouring-matter, whilst a splendid crimson aniline, when heated with corrosive sublimate, yields no is at once produced if a mixture of this base with pure aniline be treated. I reserve for a future communication the study of the colouring-matter thus obtained.

* Hofmann, D. Chem. Berichte, 1870, p. 767.

2 [[C6H2(CH3)3] (CH3)2N.HC1] .PtCl. Remarkably enough, dimethylated cumidine exhibits the same reluctance to form a quartary compound with methyliodide that has already been pointed out as a peculiarity of the tertiary xylidine. But whilst in the case of dimethylxylidine, though difficultly and sparingly, combination after all took place, all attempts with dimethylated cumidine have hitherto failed. The base was heated with methylic iodide for days in the water-bath, and ultimately even to 150° without any result. This inability of forming quartary compounds must in one way within the molecule. At all events, it deserves to be or another depend upon the arrangements of the material noticed that there are dimethylated xylidines and cumidines which readily combine with methyl iodide. The dimethylated bases existing in the less volatile fractions of commercial dimethylaniline, all form quartary compounds without difficulty, and must therefore correspond to xylidines and cumidines,which differ from those derived from trimethylated phenylammonium iodide.

In what relation stands the cumidine above described

to the cumidines already known? Of the several purely methylic cumidines which are possible, two only are somewhat accurately known; these are the two bases, which are derived, the one from so-called pseudocumol (obtained by treating xylilic bromide and methylic iodide with sodium), the other from mesitilol. The former cumidine is a solid, fusing at 62°, and need not therefore be further considered here. Most probably the cumidine above described will prove identical with the primary monamine corresponding to mesitilol. Unfortunately, mesitylamine has been hitherto so little studied, that even its boiling-point is not known. I hope next winter to examine more minutely this group of compounds.

In conclusion, I have great pleasure in expressing my best thanks to Mr. E. Mylius, assistant in the Berlin Laboratory, for the zeal and care with which he has

2 [[C6H2(CH3)3] H2.N.HCI] .PtC14.


was thus led to believe that the fraction boiling furthered the progress of these researches.

between 217° and 230° consisted of several isomeric cumidines; but on separating the bases from the several chlorhydrates, it was found that they all contributed very

nearly the same boiling-points. The liquid thus obtained NEW METHOD FOR PRODUCING AMIDES AND

boiled between 225° and 227°, and had the V.W. 0·9633;

it did

not solidify when exposed to a temperature of -10°. I am therefore inclined to assume that only one cumidine is formed by the action of heat on trimethylated phenylammonium iodide, and that the irregularities in the

SOME time since Professor Hofmannt has shown that

boiling-point of the original fraction must be due to the phenyl mustard-oil, when acted on with acetic acid under presence of small quantities of impurities.

pressure, is converted into phenyl-diacetamide, carbonic obtained from anhydride and sulphuretted hydrogen being separated

CS N + 2(C2H3O-OH)
N+ CO2 + H2S.
Bearing this reaction in mind, the question arose as to



By E. A. LETTS, Berlin University Laboratory.


* A Paper read before the Royal Society.

+ Hofmann, Beriche. d. Deutch. Chem. Gessell., 1870.

how the metallic sulphocyanates would behave under similar circumstances; at Professor Hofmann's suggestion I have submitted this question to an experimental investigation.

Action of Acetic Acid on Potassium Sulphocyanate. Supposing the potassium salt of sulphocyanic acid to undergo a change analogous to that observed with the phenyl mustard-oil, it was to be expected that I molecule of this body would react with 3 molecules of acetic acid to produce i molecule of potassium acetate and I molecule of diacetamide, carbonic anhydride and sulphuretted hydrogen being evolved--


The reaction, however, takes a different course.

In my first experiments the acetic acid was allowed to react on the sulphocyanate under pressure; but it soon became evident that this was unnecessary, simple digestion of the two bodies in a flask provided with an upright condenser being amply sufficient.

The powdered salt dissolves readily in the boiling acid, and an immediate and copious disengagement of gases ensues, in which carbonic anhydride and sulphuretted hydrogen may be readily recognised. Considerable time, however, elapses before the sulphocyanide is completely decomposed, some three or four days being required for a mixture of 100 grms. potassium sulphocyanate and 180 grms. acetic acid. At the end of this time the products

of the reaction were submitted to distillation and com-
menced boiling at 170°-180°; the thermometer, however,
rose rapidly to 216; and between this temperature and
220° the distillate solidified in the receiver to a radiating
crystalline mass, which analysis showed to be pure aceta-
midet. Above 220 nothing further distilled, the residue
in the retort consisting wholly of potassium acetamate.
In what manner had acetamide been formed, instead of
diacetamide expected in the reaction? It appeared not
unlikely that the acetic acid employed contained some
water, and that the diacetamide produced in the first
instance was thus converted into the mono-compound-
(C2H3O) 2

}}} N+H2O=C2H2O-OH + C2H3O .N.


To remove any water which might possibly have been present, the acetic acid was treated with phosphoric anhydride, and the experiment with the sulphocyanate repeated; but even now acetamide was exclusively obtained.

On submitting, however, the gases evolved during the reaction to a closer examination, the formation of acetamide became at once intelligible. It was found that a large proportion of these gases consisted of carbonic oxysulphide (COS). To prove the presence of this compound, it was only necessary to pass the evolved gases through a bottle containing a slightly acid solution of lead, by which the sulphuretted hydrogen was retained : thus purified, they produced no further precipitate when passed through a second bottle containing the same solution; but precipitation at once took place if this solution were rendered alkaline by soda or ammonia.

This is the characteristic behaviour of carbon oxysulphide, which was further identified by its odour, great density, and inflammability.

The principal reaction that takes place when acetic acid is treated with potassium sulphocyanate is accordingly as follows:


The liquid products passing over before 216° yield considerable quantities of the amide on fractionation; this remark applies to the other experiments with the fatty acids to be presently described.

The sulphuretted hydrogen and carbonic anhydride, produced simultaneously with the carbonic oxysulphide, are the complements of a second reaction; the principal product of which I have not the least doubt is acetonitrile.



I must remark, however, that I have not actually proved the formation of this body by experiment. My investigations in the acetic series were completed before this phase of the reaction was thoroughly understood, and thus, probably owing to its low boiling-point (77°), the acetontrile had been carried off with the stream of disengaged gases, and had escaped detection. I have not repeated the experiment, because in other series it has been easy to demonstrate the formation of the nitrile.

Action of Isobutyric Acid on Potassium Sulphocyanate. If potassium sulphocyanate be heated with isobutyric acid (which may now be readily obtained in a state of purity by oxidation of the isobutyric alcohol separated from fusel oil), the salt melts under the acid to an oily layer, from the surface of which bubbles of gas are plen tifully disengaged, consisting, as in the preceding case, of carbonic oxysulphide, carbonic anhydride, and sulphuretted hydrogen. In consequence of higher boilingpoint of isobutyric acid (154), the reaction proceeds more rapidly than with acetic acid. If the mixture be submitted to distillation when all disengagement of gas has ceased, it begins boiling a few degrees above 100°, the thermometer rapidly rising to 216; during this time an aromatic liquid passes over, possessing the odour of butyric acid.

Between 216° and 220° the thermometer remains tolerably constant, the distillate solidifying in the receiver to a white crystalline mass. On fractionating the liquid portion passing over before 200°, no product can be obtained showing a constant boiling-point; but on treating it with a solution of caustic soda, an oily aromatic liquid of characteristic odour floats on the surface, which, separated by a large funnel and dried over calcium chloride, boils constantly between 107° and 108°. Its composition and reactions characterise this substance as isobutyronitrile. H-C-(CH3)2 CN Theory.



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69 Boiled for some time with an alkali, this nitrile is converted into isobutyric acid and ammonia. The complementary products attending the production of this body are carbonic anhydride and sulphuretted hydrogen, whose copious evolution have already been mentioned.



Experiment. 68'93


Isobutyronitrile has been prepared by Merkownikoff.* potassium, but probably not in a state of purity, as he He obtains it by treating isopropyl iodide with cyanide of gives 80° as its boiling-point; whereas 107° to 1080, the number obtained by myself, approaches more closely that observed for the normal butyronitrile (114). The crystalline substance before described as passing over between 216° and 220° is the amide of isobutyric acid


H-C = (CH3)2

* Merkownikoff, Jahresb., xviii., 318.

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