202 ELLIOTT :

XXV.-Preparation and Properties of the Benxochloroamides.

By GEORGE ROBERT ELLIOTT.

THE author found that the action of ammonium hydroxide on benzomonochloroamide gives an almost quantitative yield of phenyl- carbamide ; as benzoylhydrazine, which might have been formed, does not undergo intramolecular change to phenylcarbamide, the formation of the latter requires some other explanation.

Blacher (Ber., 1895,28,435), by the action of iodine on sodium benzamide, obtained benzoylphenylcarbamide instead of the substituted hydrazine expected. Titherley (T., 1901, 79, 391) obtained an alkylacyl- carbamide by the action of a sodamide on a bromoamide. Folin (Amer. Chem. J . , 1897, 19, 323) and Swartz (ibid., 1897, 19, 319), by the reaction of substituted bromoamides with sodium ethoxide, obtained substituted urethanes, and not hydroxylamine derivatives.

Each of these results seems to indicate the intermediate formation of a carbimide; and up to this stage, all the reactions are probably identical with that of Hofmann for the preparation of amines from halogenoamides, which, according to Graebe and Rostovzeff (Ber., 1902, 35, 2747), passes through the following phases, where X represents a halogen atom :

R-CO-NHX + NaOH -+ R*CO*NNaX + R-NNa-COX -+

Several related anomalies have been recorded.

R*N:CO + NaX. R*N:CO + H20 + R*NH*CO,H + R*NH2 -b C02.

In the cases cited, however, it would seem that the stages subsc- quent to the formation of the substituted carbimide become modified ; thus, with benzochloroamide and ammonium hydroxide,

R*N:CO + NH, -+ R*NH*CO*NH,;

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PREPARATION AND PROPERTIES OF THE BENZOCHLOROAMIDES. 203

with iodine and the sodamide,

R*N:CO + R*CO*NHNa + R*NH*CO*NNa*COR R*NH*CO*NNa*COR + H,O -+ R*NH*CO*NH-COR + Na0l-i ;

and with sodium ethoxide and a bromoamide,

R*N:CO + EtOH + R*NH*CO,Et.

As phenylcarbimide is probably an intermediate product in all these reactions, and as it also appears to be easily formed from benzomonochloroamide, the study of the latter appeared to be of interest. Whilst attempting its preparation by the action of bleaching powder and acetic acid on benzamide (Bender, Ber., 1886,19,2274), the author found that when the amide was dissolved in moderately concentrated instead of in dilute acetic acid, the product was a heavy, yellow oil which appeared to be benzodi- chloroamide, CBH,*CO*NC1,; as this compound does not appear to have been described, some of its reactions were examined.

The investigation of benzomonochloroamide showed that in all its reactions with alkalis the chloroamide is first converted into phenylcarbimide, which then condenses with a suitable compound present. Experiment has further shown that benzomonochloro- amide can, in many cases, be employed as a source of phenylcarbimide prepared in situ; being easily obtainable and capable of being stored without deterioration, the monochloroamide may bring to more general use the great reactivity of the carbimide.

E X P E R I M E N T A L .

Preparation of Benmmorwchloroamide and of Benzodichloroamide.

Datta and Ghosh (J. Amer. Clem. SOC., 1913, 35, 1044) prepared benzomonochloroamide by chlorination for about four hours, of an aqueous suspension of benzamide, until the suspended solid had thc desired melting point. Working with an aqueous or acetic acid solution, the author obtained a crystalline precipitate of the mono- chloroamide, which on further chlorination changed into a heavy, yellow oil, which proved to be the dichZoroamide, C,H5*CO*NCI,. With a more rapid stream of chlorine, the intermediate mono- chloroamide did not appear. The action of hydrochloric acid on the oil gave the monochloroamide with evolution of chlorine ; consequently, the latter compound only is obtained by chlorination of a hydrochloric acid solution of benzamide. Good results were obtained with a saturated solution in approximately 3N-acid ; the monochloroamide separated almost immediately, and the time required for complete chlorination of 10 grams of benzamide was

H* 2

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204 ELLIOTT :

about forty-five minutes. The benzomonochloroamide thus obtained was almost pure, and after recrystallisation from hot water melted a t 117". The yield was 90 per cent. of the theoretical, exclusive of the material remaining in the mother-liquid. The advantage of this method of preparation is that a well-defined product is obtained automatically, and its purity is independent of the exact duration of the passage of chlorine.

Reactions of Benmmonochloroamide.

The action of sodium hydroxide and of sodium carbonate on benzomonochloroamide has been elucidated by Hofmann (Ber., 1882, 15, 756), Graebe and Rostovzeff (bc. cit.), and Mohr ( J . pr . Chem., 1905 [ii], 71, 133; 72, 297) with reference to the formation of aniline, diphenylcarbamide, and benzoylphenylcarbamide.

The conditions for the preparation of the latter two substances are difficult to define, as the temperature, and more especially the concentrations of alkali and chloroamide, determine the nature of the final product.

According to the author's observations, the formation of diphenylcarbamide requires a dilute solution of the chloroamide (at the most 2 grams per 100 C.C. of total solution) and N/5-sodium hydroxide solution ; whilst benzoylphenylcarbamide requires a more concentrated solution of the chloroamide (at least 2 grams per 40 C.C.

of total solution) and N/Z-sodiurn hydroxide solution. The results of a few experiments a t the ordinary temperature

are appended :

Conc. of alkali. 2N. C.C. of solution'

per gram of I 6 chloroamide 1

Result with Benzoyl-

amide. NaOH. phenylcarb-

Result with 9 )

Na,CO,

2N. 0.0N. 0.2N.

60 20 60

Diphenylcarb- Benzoyl- Diphenylcarb- amide and phenylcarb- amide and

traces of amide. traces of aniline. aniline. - 9 9 Benzoyl-

phenylcarb- amide.

In each case the substituted carbamide separated in needles, the reaction being slower in the case of diphenylcarbamide than in that of benzoylphenylcarbamide, which was produced within a few minutes.

Phenylcarbimide is formed in each case, the divergence being in its subsequent reactions. The transformation into aniline (compare Hofmann's reaction) wil l affect only a part of the phenylmbimide

The yields were almost theoretical.

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PREPARATION AND PROPERTIES OF THE BENZOCHLOROAMIDES. 205

if less concentrated alkali be used, and the aniline formed will then react with the remainder to give diphenylcarbamide. In the forma- tion of benzoylphenylcarbamide the phenylcarbimide does not reach the aniline stage, but, according to Stieglitz and Earle (Amer. Chem. J . , 1908, 30,412), reacts with unchanged benzomonochloro- amide thus :

C,H,*CO~NC1~COoNH~C,H, + NaOH = C6H5*CO*NHC1 $- C,H ,*N:CO = C6H ,*COeNC1*CO *NH*C ,H 6.

C , H 5 * C O ~ ~ H ~ C O ~ ~ H ~ C 6 H , + NaOCl. Benzomonochloroamide dissolves readily in ammonium hydroxide

solution with development of heat, and on cooling, colourless needles of phenylcarbamide separate ; these, after recrystallisation from water, melt a t 147". A 90 per cent. yield of the pure substance (m. p. 147') is obtained after the mother-liquor has been evaporated.

As ammonium hydroxide no doubt first reacts as an alkali to give phenylcarbimide, a stream of dry ammonia was next passed into a warm benzene solution of the chloroamide. This caused the immediate separation of colourless needles (m.p. about 106" with loss of ammonia), which could not be recrystallised from warm solvents owing to decomposition into ammonia and benzomono- chloroamide. This product was the ammonium salt of the chloro- amide, C,H,*CO*NCl*NH4 ; it dissolved completely in cold water, but after some time a white precipitate separated. At room temperature the precipitation required several hours for completion, but at higher temperatures the product was dark in colour. The aqueous solution contained ammonium chloride and was acid to litmus; during the reaction, carbon dioxide was formed, and the presence of a little aniline indicated the intermediate formation of phenylcarbimide. After several recrystallisations from benzene, the precipitate melted at 208" (Found : N = 16.65 per cent.); it was hydrolysed by sodium hydroxide solution giving ammonia, aniline, and carbon dioxide, but no benzoic acid.

These facts show the compound to be s-diphenylbiuret, NH(CO*NHPh), (m. p. 208-210".

The above reaction is not influenced by the presence of a large excess of ammonium chloride, and therefore the intermediate formation of phenylcarbamide from phenylcarbimide and ionised ammonium chloride is improbable, since excess of the latter would then give phenylcarbamide as the final product.

The reactions which occur are possibly those indicated below :

Calc., N = 16-45 per cent.).

C6H~°CO'NC1'~4 --j. C6H,*N:CO + NHdC1. C,H,*CO*NC1*NH4 + C,H,*N:CO +

C,H 5*CO*NC1*NH,*C0 *NH C6H5.

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206 ELLIOTT :

The product, undergoing the usual Beckmarin transformation, may give the biuret with or without fission to, and subsequent condensation of , phenylcarbimide and phenylcarbamide hydro- chloride :

C6H5*13; *O*NH,*CO*NH*C,H, C1-g *O*NH3*CO*NH*C,H,

--+ C,H,*NH*CO*NH*CO*NH*C,H5 + HC1.

Swartz (Eoc. cit.) founcl that) sodiiini ethoxide in alcoholic solution reacts with benzobrornoamide to give a mixture of benzamide, phenylurethane, and benzoylphenylcarbamide, the principal reaction in concentrated solution being reduction of the bromoarnide, and, in dilute solution, the formation of the urethane.

The author's experiments show that this reaction is slightly modified in the case of benzochloroamide owing to its greater stability. No reduction to benzamide was discovered, and the nature of the product was determined, not I,y the concentration, but by the amount of alkali used.

Experiment I.-When equivalent quantities of sodium ethoxide and the chloroamide were employed, sodium chloride separated and phenylurethane remained in solution.

Experiment 1 I . W h e n two equivalents of sodium ethoxide were employed, sodium chloride separated first, and then a magma of needles consisting of the sodium compound of phenylurethane, C,H,*"a*CO,~t (phenylurethane separated immediately on addition of water to this compound).

Experiment III.--With half an equivalent of sodium ethoxide, benzoylphenylcarbamide was obtained, the phenylcarbimide having condensed with unchanged benzochloroamide even in presence of excess of alcohol.

By adding sodium hydroxide solution drop by drop to a mixture of the chloroamide and a slight excess of phenol suspended in a little water, with constant shaking in the cold, a magma of needle- shaped crystals was obtained ; this compound, on recrystallisation from benzene, melted a t 126", and proved to be phenyl phenyl- carbamate, C,H,-NH*CO*O*C,H,.

An attempt to prepare the hydrazine, ~ 6 ~ , < ~ ~ > ~ * ~ ~ ~ ~ ~ ~ ~ , ~ 5 ,

was made by treating the chloroamide with potassium phthalimide in alcoholic solution ; but the precipitate which was rapidly formed crystallised from alcohol in colourless needles melting a t 140°, and

C1 N C,H,*N

proved to be phthalylphenylcarbamide, C,H,<CO>NoCO*NH.C6H5, co which has not previously been described.

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PREPARATION AND PROPERTIES OF THE BENZOCHLOROAMIDES. 207

The action on the chloroamide of ethyl sodiomalonate suspended in benzene was examined in order to discover if the phenylcarbimide produced would react with the enolic form of ethyl malonate; but even in absence of sodium ethoxide, benzoylphenylcarbamide was obtained. The reaction was evidently :

and the phcnylcarbimidc then formed through the usual scries of reactions, combined with iinchanged chloroamide.

Equivalent quantities of sodium and benzochloroaruicte were heated together under reflux for two hours in dry benzene solution. Sodium chloride separated, and on cooling, benzoylphenylcarbamide was deposited; no evidence of the presence of a hydrazine was obtained. As no alkali was present, the equations for the formation of benzoylphenylcarbamide by the action of sodium hydroxide require modification; and to conform with the facts discovered by Stieglitz and Earle (Zoc. cit .) , that phenylcarbimide will not condensc with acid amides, although it does so readily with acid halogeno- amides, the simplest representation of the reaction seems to be :

C,H,*CO*NHCI + Na -+ C,H,*CO*NNaCl + H +

C,H,*CO*NHCl + C,H,*N:CO -+ C,H,*CO*NCl*CO*N~*C,H,. C,H,*CO*NCl*CO*NH*C,H, + H, +

C,H,*N:co -+ ILaCl+ H.

C,H,*CO*NH*CO*NH*C,H, + HC1.

Benzochloroamide was heated under reflux with excess of dry benzene in the presence of anhydrous aluminium chloride for several hours, in an attempt to obtain benzanilide. Hydrogen chloride was evolved, but the main product proved to be benzamide; in absence of aluminium chloride, the chloroamide remained unchanged.

The main product of the action of aniline on benzochloroamide proved t o be benzanilide, and no substituted hydrazine was formed. When dimethylaniline was employed, the mixture passed through shades of green and blue, to give, finally, a violet solution which, on cooling, deposited crystals. This compound, purified by dis- tillation, proved t o be benzamide. The violet coloration was due t o the formation of traces of methyl-violet, which according to Brunner and Brandenburg (Ber., 1877, 11, 697), is produced by the action of bromine on dimethylaniline.

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208 ELLIOTT :

The Use of Benxochloroamide as a Substitute for Phenylcarbimide.

The experiments on the action of sodium ethoxide and of sodium phenoxide on benzochloroamide have indicated the procedure necessary to bring about the condensation of the phenylcarbimide formed, with a compound containing an alcoholic or a phenolic hydroxyl group. The preferential condensation of the phenyl- carbimide with excess of the chloroamide in presence of alcohol further indicated that alcohol could be used as an indifferent solvent, and sodium ethoxide as alkali, provided that the compound with which it was desired to bring about condensation were an amino- compound present in slight excess.

In an attempt to prepare phenyl-p-tolylcarbamide from p- toluidine and benzochloroamide, the use of sodium hydroxide with an aqueous or dilute alcoholic solution of the mixed compounds was unsuccessful ; but by dissolving the mixture in alcohol and then adding an alcoholic solution of sodium ethoxide, a crystalline mass was obtained which proved to be phenyl-p-tolylcarbamide (m. p.

Combination with aniline was found to take place in aqueous solution. Thus diphenylcarbamide was most simply prepared by warming a dilute sodium hydroxide solution of the chloroamide in presence of an equivalent quantity of aniline; the yield was almost quantitative.

These results seem to indicate that although preliminary experi- ment is necessary to ascertain the best conditions for the condensation to take place, benzomonochloroamide can be used, in many cases, as a source of phenylcarbimide prepared in situ.

212").

Reactions of Benmdichloroamide, C ,H ,-CO*NCl,.

This compound, which is a heavy, yellow oil, proved to be very unstable, and on exposure to air for several days lost chlorine continuously, giving benzomonochloroamide. It readily converted benzamide or acetamide to the monochloroamide. With hydro- chloric acid and with sulphurous acid it gave the monochloroamide, a vigorous evolution of chlorine taking place in the former case. It gradually dissolved, apparently unchanged, in concentrated sulphuric acid, but on dilution with water, chlorine was evolved and the monochloroamide separated.

The dichloroamide dissolved in cold sodium carbonate solution, slowly and with evolution of carbon dioxide and nitrogen. On acidifying the solution, a precipitate of benzoic acid was obtained. On boiling the sodium carbonate solution with sodium hydroxide,

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PREPARATION AND PROPERTIES OF THE BENZOCHLOROAMIDES. 209

no aniline was formed ; the possibility of the formation of sodiobenzo- chloroamide as an intermediate compound was thus excluded, since Hofmann’s reaction would then have progressed. The oil dissolved much more quickly in dilute sodium hydroxide solution, with development of heat and evolution of nitrogen. In the early stages of the reaction an odour of benzonitrile was noticeable, but this was soon masked by an overwhelming odour of the carbylamine. A little aniline was obtained by distilling the alkaline solution in steam, indicating the formation of phenylcarbimide at some stage. By acidifying, benzoic acid was obtained at all stages, even before the odour of the carbylamine became evident.

Assuming the oil to be benzodichloroamide, its action with alkalis is readily explained. Displacement of chlorine atoms by hydroxyl groups probably first occurs, and the unstable compound C6H5*CO*N(OH), can then decompose in the three ways yielding

(1) C6H,*CN + 0, + H,O, (2) C,H,*NC + 0, + H,O, and (3) C,H,*N:CO + 0 + H,O,

the phenylcarbimide in (3) being formed either directly or by oxidation of the carbylamine. The reaction with sodium carbonate solution appears to be confined to reaction (1) ; but sodium hydroxide solution gives all three products. The formation of nitrogen is explained by the oxidation of the ammonia liberated in the hydrolysis of benzonitrile to benzoic acid.

The action of ammonium hydroxide on the oil gave phenyl- carbamide with development of heat ; the formation of nitrogen trichloride, indicated by a flash in the tube, confirmed the preliminary reduction of the dichloroamide to the monochloroamide requisite for the production of the phenylcarbamide.

The evidence of a chlorine estimation cannot be taken as conclusive evidence of the chlorine content of the oil, owing to the continuous loss of chlorine making impossible the choice of a sample free from dissolved chlorine, yet undecomposed. A sample which had been exposed to the air for two days gave C1= 35 per cent. (Calc., C1= 37.3 per cent.).

In conclusion, the author wishes to express his indebtedness to

THE CHEMISTRY DEPARTMENT,

Professor F. S. Kipping, F.R.S., for his interest in this work.

UNIVERSITY COLLEGE, NOTTINGEAM. [Received, June 23rd, 1921. J

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