292XXXI .- TheCHATTAWAY AND CHANEY :Action of Chlorine on Phen y 1 car bamide.By FREDERICK DANIEL CHATTAWAY and NEWCOMB KINNEY CHANEY.THE action of chlorine on phenylcarbamide is of necessity a com-plicated one, since each of the three hydrogen atoms attached t onitrogen in the compound can be exchanged for halogen, which can alsopass into the nucleus by intramolecular rearrangement when thehydrogen of the imino-group connecting the carbonyl and phenylgroups is replaced.The isolation of the various compounds produced is rendereddifficult and in eome cases impracticable by the circumstance that thegroup *CO.NHCI, which is comparatively stable in presence of hydro-chloric acid, a t once breaks down with liberation of nitrogen iTHE ACTION OF CHLORINE ON PHENYLCARBAMIDE.293presence of alkali carbonates, whilst the group *CO*NCl*C,H,, which i jcomparatively stable in presence of the latter, undergoes isomericchange under the influence of hydrochloric acid.Hence, since chlorination has to be effected in acid solution, deriv-atives containing the unsubstituted phenyl residue, although un-doubtedly formed, have not been isolated in a pure state; indeed, onlywhen the phenyl group contains chlorine in all available positions canany considerable number of the N-halogen compounds theoreticallypossible be obtained.The action of chlorine on phenylcarbamide is interesting, as thehalogen passes with great ease at the ordinary temperature, not onlyinto the para- but into both ortho-positions, whilst with acyl anilidesthe final transformation, in which the halogen enters the second ortho-position, is only effected with some difficulty a t a comparatively hightemperature.The N-halogen derivatives obtained are also of more than ordinaryinterest on account of their unexpectedly great stability, for examp:e,2 : 4 : 6-trichlorophenyltrichlorocarbamide can be heated to a tempera-ture approaching 130° without decomposition.A consideration of the properties of the N-chloro-derivativesobtained leads to the conclusion that chlorine enters preferably theamino-group, the hydrogen of the *NH*G,H, group being nextreplaced thus :NH,*CO-NHPh -+ NHCl-CO*NHPh -+NHCl*CO*NClPh -+ NCl,*CO*NClPPh.The entrance of halogen into the nucleus follows the regular coursethe para- and ortho-positions being taken up, until finallyall three areoccupied by halogen.EXPERIMENTAL.Action of Chlorine and of Hypochlorous Acid on Phsnylcarbamide.The N-chloro-derivatives derivable from unsubstituted phenyl-carbamide are undoubtedly formed when chlorine is passed into asolution of phenylcarbamide in glacial acetic acid containing an excehsof sodium acetate, but halogen enters the phenyl group with S U C ~ Areadiness that they have not been isolated.The considerable evolutionof heat which takes place in this action is caused by the entrance ofhalogen into the ring, since only a very slight development of heat iscaused by the replacement of hydrogen in carbamide by halogen.If to a strongly-cooled solution of phenylcarbamide in alcohol thecalculated quantity of N/10 aqueous hypochlorous acid is added, aN-chloro-derivative separates in the form of a somewhat viscid solidThis dissolves easily in chloroform, and is left on evaporation of th294 CHATTAWAY AND CHANEY :solvent as a slightly brown, viscid mass, which, without doubt, consistsmainly of the compound NCl,*CO*NClPh, as it contains almost thotheoretical amount of chlorine attached to nitrogen and is transformedinto a mixture of substituted phenylcarbamides on keeping a solutionin glacial acetic acid for some hours, We have not, however,succeeded in bringing it in to a crystalline condition.SubstitutedN-chloro-derivatives, although crystallising well from chloroform orpetroleum when perfectly pure, can only with great difficulty be madeto crystallise when they contain even slight amounts of impurity,especially when, as in the case of those containing unsubstitutedphenyl groups, they are of low melting point.A similar result was obtained when phenylcarbamide suspended inwater was chlorinated in presence of excem of calcium carbonate.p- Chlorophen ylcl~lorocccrbamide, N HCl* GO* N H C,H,CI,This compound can be prepared by thecareful chlorination of phenyl-carbamide or of p-chlorophenylcarbamide dissolved in glacial aceticacid in presence of excess of sodium acetate.Five grams of p-chloro-plienylcarbamide were dissolved in 250 grams of glacial acetic acid, andfinely powdered, crystalline sodium acetate was added so long as it wasdissolved.This liquid was cooled i n ice to as low a temperature aspossible without crystallisation of the glacial acetic acid, and a slowstream of chlorine passed in. p-Chlorophenylchlorocarbamide separatedin small, colourless needles. The stream of chlorine was stoppedbefore the whole of the p-chlorophenylcarbamide had been cmvertedinto the N-chloro-derivative, and the latter was collected, washed wellwith water and finally with chloroform, and dried in a vacuum overphosphoric oxide. It crystallises from warm chloroform, in which it issparingly soluble, in colourless, fine needles. When heated it remainsapparently quite unchanged until 122O, when it suddenly decomposeswithout previously melting. When treated with hydriodic acid, iodineis quantitatively liberated, and p-chlorophenylcarbamide, identical withthat obtained from potassium cyanate and p-chloroaniline, is formed.It and the other N-chloro-derivatives described in this paper wereanalysed by the method generally applicable to nitrogen chlorides, byadding known quantities to solutions of potassium iodide containingglacial acetic acid and titrating the iodine liberated with N/lO-sodiumt hiosulphat e :0,1083 liberated iodine = 10.4 C.C.N/10 I. C1 as :N@l= 17.02.C7H,0N,CI, requires Cl as :NCI = 1'7.29 per centTHE ACTION OF CHLORINE ON PHENYLCARBAMTDE. 295p-Chlorophertyldichlo~~~r~a~~de, NCla.CO*NH*C,H,CI.This compound separates as a pale yellow solid when the calculatedamount of an aqueous solution of hypochlorous acid i s rapidly addedt o a solution of phenylcarbamide in glacial aoetic acid.It crystallisesfrom warm acetic acid, in which it is readily soluble, in pale yellowneedles, which soften a t about 85' and melt and decompose a tabout 90° :0.1804 liberated iodine = 30.3 C.C. N/10 I.The yellow colour of the compound indicates that in it two chlorineC1 as :NCI= 29.77.C7H,0N,C13 requires C1 as :NCI = 29.6 per cent.atoms are attached to the same nitrogen atom.p-Chlorophenylt~&chZorocarbam~d~, NCl, G0.N C!1* C,H,CI.This compound is formed when chlorine in excess is passed into acooled solution of p-chlorophenyloarbamide in glacial acetic acid inpresence of excess of sodium acetate. The insoluble N-monochloro-derivative first formed slowly dissolves as the passage of the chlorineis continued, and the N-trichloro-derivative is obtained as a paleyellow, viscid liquid by diluting with water, extracting with chloroform,and removing the solvent in a ourrent of dry air.This liquid always gave on analysis a somewhat too low peroentageof chlorine as :NCI, and itlhas never been brought into a orysta.llinecondition.This is probably due to it never having been obtainedperfectly pure, but always mixed with a small amount of the corre-sponding N- trichloro-derivative of 2 : 4-dichlorophenylcarbamide, thepassage of the chlorine having to be continued so long to effect thesolution of the N-monochloro-derivative that transfer of chlorine intothe phenyl group in the ortho-position always takes place to a smallextent.2 : 4-Dichlorophenylrnonochlorocarbamide, NHC1-CO*NH*C,H3CI,.This compound is formed when equivalent amounts of 2 : 4-dichloro-phenylcarbamide and of its N-dichloro-derivative are dissolved in assmall a quantity as possible of warm glacial acetic acid.On cooling,2 : 4-dichlorophenylmonochlorocarbamide separates in needle-shapedcrystals. It crystallises from hot chloroform, in which it is sparinglysoluble, in long, colourless, silky needles. When heated it decomposes at132", giving off bubbles of gas and fusing to a brown mass :0.2215 liberated iodine = 18.7 C.C. N/10 I. C1 as :NCI= 14.96.C7H,0N,C13 requires C1 as :NC1= 14.8 per cent296 CHATTAWAY AND CHANEY :2 : 4-DichZorop~eny~dic~lorocarbanzide, NCI,-CO*NH*C,H 3C12.2 : 4-Dichlorophenyldichlorocarbamide can be prepared either fromphenylcarbamide or from p-chlorophenylcarbamide, and as i t is easilysoluble in chloroform and crystallises well, it can be separated withoutdifficulty from any small admixture of other products which may beformed together with it.It is most readily prepared by dissolving phenylcarbamide in fromtwelve to fifteen times its weight of glacial acetic acid, adding twoequivalents of powdered sodium acetate, and passing chlorine until theliquid is saturated.'J'he liquid should be cooled as far as possibleduring the passage of the gas so that it never becomes even slightlywarm. After filtering off, if necessary, a small quantity of 2 : 4 : 6-tri-chlorophenylmonochlorocarbamide, which is occasionally formed ifthe chlorination has been continued too long, cooled chlorine-wateris added in excess, when the N-dichloro-derivative separates as a yellowsolid or as a yellow liquid which quickly crystallises. To obtain i tdry and free from adhering acid, it is best to add sufficient chloroformt o dissolve it, shaking vigorously, then, after washing repeatedly withchlorine-water, separating, and drying the chloroform solution overfused calcium chloride, to drive off the solvenl in a current of warmdry air, A yellow, crystalline solid separates as the chloroformvolatilises, or if crystallisation does not a t once take place, this can bebrought about by stirring the deep yellowish-coloured oil with a littlepetroleum of very low boiling point.It can be similarly easilyprepared from p-chlorophenylcarbamide or 2 : 4-dichlorophenyl-carbamide, but as these are somewhat difficult to procure it is best t oproceed as described above.It crystnllises well from hot chlcroform, in which it is readily soluble,in pale yellow, four-sided, rhombic prisms. It melts at 7 6 O ; whenheated above this temperature, it remains apparently unchanged upt o 100-105", when it begins to give off gas; the gas evolution is a tfirst veiny slight, but it increases in amount as the temperature risesuntil the neighbourhood of 120" is reached, when slight cracklingexplosions generally occur, due to the evolution and explosion ofvapour of nitrogen chloride :0.3897 liberated iodine= 56.8 C.C.N/10 I-,C7H,0N2C1, requires C1 as :NCI = 25.68 per cent.As this compound shows a yellow colour as intense as that ofnitrogen chloride, it seems probable that both the chlorine atoms notin the nucleus are attached to the same nitrogen atom, since phenyl-carbamide derivatives, which contain only one chlorine atom attachedt o nitrogen, and the dichloro-derivative of carbamide itself, whichCl as :NCl= 25-84THE ACTION OF CHLORINE ON PHENYLCARBAMIDE. 297contains two *NHCl groups, are without appreciable colour. It seemslikely that this and the similarly-constituted derivative of p-chloro-phenylcarbamide are formed by the intramolecular rearrangementof phenyltrichlorocarbamide and p-chlorophenyltrichlorocarbamiderespectively, thus :NCl,*CO*NClPh -+ NCl,~CO*NH*C,H,Cl andNCl,* COD N C1*C6H,Cl -+ NC12* CO NH.C,H,CI 3.2 : 4-Dichloropheny?-s-dichZorocarbc~mide, NHCl*CO*~C1*C,H,C12.If 2 : 4-dichlorophenyldichlorocarbamide is dissolved in chloroformand the solvent allowed slowly to evaporate, tufts of slender, colour-less prisms are deposited. These can be recrystallised from chloro-form, but have never been obtained perfectly pure, as they readilychange into 2 : 4 : 6-trichlorophenylmonochlorocarbamide, from whichthey cannot b completely freed. Different specimens were found tomelt not very sharply about 80-85O, and t o contain amounts ofchlorine as :NCl varying from about 23.5 to 24.5 per cent., thisbeing from 1 to 2 per cent. too low for the pure substance. Thus thecoloured, unsymmetrical N-dichloro-derivative when in solutionappears slowly to become converted into the colourless, symmetricalderivative, which very easily undergoes transformation into 2 : 4 : 6-trichlorophenylmonochlorocarbamide :NC12*CO*NH*C6H3CI, -+ NHC1*CO*NC1*C6H3C1, --tNHCl*CO*NH* C6H2C13.2 : 4 : 6- Trich Zorophe~zyZmonochZo~ocarbamide, NHC1.CO *NH* C6H2C1,.This, on account of its stability and very sparing solubility in glacialacetic acid, is the most easily prepared of all the N-chloro-derivativesof phenylcarbamide. It is formed when ,either phenylcarbamide,p-chlorophenylcarbamide, or 2 : 4-dichlorophenylcarbamide is dissolvedin acetic acid and chlorine passed into the liquid for any considerableperiod. It may be conveniently obtained as follows : Five grams ofphenylcarbamide are dissolved in about 25 grams of glacial acetic acid,and a rapid stream of chlorine is passed into the solution, cooling bywater SO that the temperature does not rise above ZOO.After thechlorine has been passing for an hour or thereabouts, fine colourlesscrystals of 2 : 4 : 6-trichlorophenylmonochlorocarbamide make theirappearance in the liquid, and slowly increase in quantity as thepassage of the gas is continued. When the separated solid no longerappears t o increase in amount, it is collected and washed well withcold glacial acetic acid and afterwards with chloroform. A furtherquantity of a somewhat impure product can be obtained by adding a littl298 THE ACTION OF CHLORINE ON PHENYLCARBAMIDE.water to the filtrate.It crystallises from warm glacial acetic acid, inwhich it is sparingly soluble, in small, very slender, hair-like crystals.When heated it turns brown, and begins to decompose at about 150°,and, if rapidly heated, further melts and decomposes at about155-156O. When dry, it can be kept for a long period at theordinary temperature without decomposition :0.2682 liberated iodine=30.1 C.C. N/10 I. C1 as :NC1= 13.28.C7H,0N,C14 requires C1 as X C l = 12.94 per cent.2 : 4 : 6-TrichlorophenyZcarbamide, NH,*CO~NH*C6H2Cl,.This compound is most easily obtained by replacing the N-halogenatom in 2 : 4 : 6-trichlorophenyimonochlorocarbamide by hydrogen.Five grams of 2 : 4 : 6-trichlorophenylmonochlorocarbamide weresuspended in 20 C.C. of glacial acetic acid, and 2 grams of powderedpotassium iodide added.The iodine liberated was removed as fast asit was formed by adding an aqueous solution of sodium sulphite,When iodine was no longer liberated, a slight excess of sulphitesolution was added, the liquid was warmed for some time on a water-bath, and kept for twenty-four hours. The 2 : 4 : 6-trichlorophenyl-carbamide thus formed was then collected and recrystallised fromalcohol. It separates from boiling alcohol, in which it is moderatelyeasily soluble, in colourless, long, hair-li ke crystals, When heatedrapidly it melts at 250°, and decomposes and evolves gas at a slightlyhigher temperature :C1= 44-24, 0.1422 gave 0.2545 AgCl.C7H,0N,CI, requires GI = 44-42 per cent.2 : 4 : 6-TrichEorophenyZdichZoroca~bam~de, NHCI*CO*NCI* C,H,CI,.This and the N-trichloro-derivative are best obtained from pure 2 : 4 : 6-trichlorophenylcarbamide.Five grams of 2 : 4 : 6-trichlorophenyl-carbamide were dissolved in 500 grams of cold glacial acetic acid, anda rapid stream of chlorine passed in for about ten minutes until thechlorine escaped freely. The clear yellow liquid thus produced wasdiluted with an equal bulk of water and extracted with chloroform.The chloroform solution was thoroughly washed with water, driedover fused calcium chloride, and the solvent driven off by a current ofwarm dry air. A very pale yellowish-coloured oily liquid was thusobtained, which on stirring with a little light petroleum deposited awhite solid in fine granular crystals.This was recrystallised from hotchloroform, in which it is sparingly soluble, and separates in colourless,probably orthorhombic prisms terminated by dome or pyramidal faces.On being beated it remains apparently unchanged up to 128O, when it;begins to decompose with crackling explosions without previouslHARDING AND WEIZMANN : LV-NONYLENIC ACID. 299melting. A t this point chlorine is evolved, and it seems probable thatthe explosions are due to the liberation of the vapour of nitrogenchloride, which explodes as soon as it is formed, setting free chlorine :0.2111 liberated iodine= 27.5 C.C. N/10 I.C7H,0N2Cl, requires C1 as :NC1= 22.99 per cent.The circumstance that this compound is colourless leads to theconclusion that the two chlorine atoms attached to nitrogen are notattached to the same nitrogen atom, as does also its relatively highmelting point.C1 as :NCl=22-93.2 : 4 : 6- TrichloroZ.henyEtri~o~~ocarbccmide, NC12*CO*NC1*C6H2CI,.Four grams of 2 : 4 : 6-trichlorophenplcarbamide were mixed withabout 8 grams of finely powdered sodium acetate and suspended in50 grams of glacial acetic acid. The liquid was kept cool, and a slowstream of chlorine was passsd in for an hour. The solution was thenfiltered, diluted with chlorine water, and extracted with chloroform.The chloroform extract was then repeatedly shaken with a cooledsolution of chlorine water containing a little sodium acetate. Onseparating, drying with fused calcium chlcride,and driving off the chloro-form in a current of warm dry air, a deep yellowish-coloured, viscidliquid was obtained. On dissolving this in warm petroleum of lowboiling point and keeping the solution for some hours, 2 : 4 : 6-tri-chlorophonyltrichlorocarbamide separated in bright yellow, short,glistening prisms.It melts a t 58", and can be heated to 130° without, apparent changeWhen heated above this temperature, bubbles of gas are liberated, andin the neighbourhood of 155O it darkens and completely decomposes :C7H20N,CI, requires C1 as :NCl= 31.02 per cent,0.2209 liberated iodine = 38-55 C.C. N/10 I. C1 as :NCl= 30.90.UNIVERSITY CHEMICAL LABORATORY,OXFORD