LEVY: THE ACTION OF AMINO-ACID ESTERS, ETC. 27111.-The Action o,f Amino-acid Esters on EthylDicarboxyglutaconate.By STANLEY ISAAC LEVY.WHEN ethyl dicarboxyglutaconate, CH(CO,Et),*CH:C(CO,Et),, ofwhich the sodium derivative is obtained by the action of chloroformon ethyl sodiomalonate (Conrad and Guthzeit, Annalen, 1883, 222,256), is allowed to remain for some days with concentrated aqueousammonia, i t decomposes, with elimination of ethyl malonate, form-ing ethyl aminomethylenemalonate, NH2*CH:C(C0,Et), (Ruhemannand Morrell, T., 1891, 59, 744). The mechanism of this change,and the actions of various ammonia derivatives on ethyldicarboxyglutaconate, have been studied by Ruhemann and hispupils, and it has been found that the reaction is one of verygeneral application ; thus analogous derivatives have been obtainedby the action of aniline and aromatic diamines, primary andsecondary aliphatic amines and diamines, hydroxylamine, hydr-azine, phenylhydrazine, piperidine, etc. (compare Ruhemann andMorrell, T., 1892, 61, 791; Ber., 1894, 27, 2743; Ruhemann andMiss Sedgwick, Ber., 1895, 28, 822; Ruhemann, Ber., 1897, 30,821, 1083; Ruhemann and Hemmy, Ber., 1897, 30, 2022).Thereaction has now been extended to amino-acid esters, and it isfound to apply generally to a-amiuo-compounds of this class.The change takes place very readily when a solution of ethylsodiodicarboxyglutaconate in boiling alcohol is treated with thecalculated quantity of the ester hydrochloride in the same solvent;the yellow colour of the sodium compound is rapidly discharged,with separation of sodium chloride.In the case of ethyl glycinehydrochloride, for example, the reaction is expressed by theequation :CO,Et.CH,*NH,,HCl + CNa(CO,Ef),*CH:C(CO,Et), =CO,Et*CH2*NH*CH:C((3'O,Et), + Cs(COaEt), + NaC128 LEVY: THE ACTION O F AMINO-ACIDethyl glycylmethylenemalonate, together with ethyl malonate, beingobtained. Analogous derivatives have been prepared, by the samemethod, from the ester hydrochlorides of alanine, aminobutyric,and aminoisobutyric acids, and leucine ; but whereas the glycinecompound is a colourless, odourless, crystalline solid, melting at98-99O, the homologues hitherto obtained are yellow, viscous oils,which show no tendency to solidify, and possess de'finite odoursrecalling that of mustard oil.The reaction has been shown to takeplace also with the ester hydrochlorides of tyrosine, aspartic acid,and o-aminobenzoic acid; the products in these cases also areyellow oils, but since they decompose when distilled in a vacuumit has been impossible to obtain them in the pure state.I n chemical behaviour the new derivatives very closely resembleethyl aminomethylenemalonate, of which a further examinationhas been made in an effort to prepare from i t some saturatedderivatives. Several attempts have been made to reduce this sub-stance, with the view of establishing a more convenient synthesisof B-alanine, according to the scheme :NH,*C'H:C(CO,Et), + NH,*CH,*CH(CO,Et), +NH,*CH,*CH(CO,H), -+ NH2*CH,*CH,*C02H,but none has been successful.On account of the ease with whichthe compound decomposes in acid or alkaline solutions, neutralreducing agents have been employed; but zinc aiid magnesium, inthe presence of neutral salts, the zinc-copper couple, aiid finallyhydrogen in the presence of colloidal palladium, are all withouteffect. Bromine in glacial acetic acid in the cold causes hydrolysis,according to the equation:NH,-CH:C(CO,Et), + Br, + 2H,O =NH,Br -1- H*CO,H + CHBr(CO,Et), ;it similar decomposition occurs when dry hydrogen chloride ispassed into the benzene solution. The ester is equally sensitive tothe action of alkaline reagents ; when treated with sodium ethoxidein absolute alcohol solutioii it decomposes, with evolution ofammoniz, and separation of ethyl sodiomalonate.Ethyl glycylmetliylenemalonate and its homologues show a closeparallel with this behaviour.They dissolve readily in cold concen-trated sulphuric and hydrochloric acids, giving solutions fromwhich the various products of hydrolysis are obtained on dilution ;they are not attacked by neutral reducing agents, and are decom-posed by alkalis and by bromine in the cold. When heated withaniline they decompose according to the equation (for the glycinecompound) :COaEt*CH,*NH*CH:C(C0,Et)2 i- 2C6H5*NH2 =CO,E t*CB,*NH2 + C6H,-NH*CH: Cf C0,E t) *GO -NH*CbH, + E t OHESTERS ON ETHYL DICARBOXYGCUTACONATE. 29yielding the amino-acid ester and the monoanilide of ethyl anilino-methylenemalonate in precisely the same way as ethyl amino-methylenemalonate, when heated with aniline, gives ammonia andthe monoanilide (Ruhemann and Rtorrell, Ber., 1894, 27, 2743).EXPERIMENTAL.Ethyl GlycylnieIJL?/Zen?.alonate, CO,Et*CH,*NH*CH:C(CO,Et),.A solution of ethyl sodiodicarboxyglutaconate (7.1 grams) inboiling alcohol is treated with ethyl glycine hydrochloride (3 grams,1 mol.), dissolved in the same medium.Sodium chloride begins toseparate a t once, and the yellow colour of the solution is rapidlydischarged. The mixture is heated on the water-bath until thealcohol Bas been almost completely removed; on addition of waterthe sodium chloride dissolves, leaving an oil, which sets almost a tonc0 to a mass of crystals. The solid is collected by the aid of thepump, ethyl ma-lonate passing through with the filtrate; the solidis then dissolved in hot dilute alcohol, from which it separates oncooling in colourless prisms melting a t 97-98O:0.2027 gave 0.3900 CO, and 0.1272 H,O.C,,H,,O,N requires c? = 52-76 ; H = 6-96 per cent.The ester is very readily soluble in ether or alcohol; on dilutingthe alcoholic solution with water, it separates as an emulsion, whichsolidifies on keeping.The amide, NH,*CO*C€12*NH*CH:C(@0,Et),, is obtained ondissolving the ester in concentrated aqueous ammonia; after keep-ing for a short time, the solution sets t o a semi-solid.The amideis collected and crystallised from boiling water, in which it isreadily soluble; on cooling it separates in colourless needles, whichsoften a t 178O and melt and decompose a t 180-181°:C=52*47; H=6*97.0.2053 gave 0.3705 CO, and 0.1205 H,O.C'= 49.21 ; H = 6-52.0.1970 ,, 19.8 C.C. N, at 2 3 O and 771 mm. N=11*50.C,oH,60,N, requires C=49.18; H=6*55 ; N = 11.47 per cent.The amide dissolves a t once in cold concentrated sulphuric acid,forming a greenish-yellow, fluorescent solution ; on pouring on iceafter two days, it is deposited unchanged, but if the solution iswarmed, it darkens rapidly, and decompoeition occurs.E: t h y 1 A lan ylme tlhyl ertemal onat e, CO,Et* CHMe*NH*CH : C(C0,E t)z.When ethyl sodiodicarboxyglutaconate (7.0 grams), dissolved inboiling alcohol, is treated with ethyl a-alanine hydrochloride(3.2 grams, 1 mi.) thg colour is discharged, and sodium chlorideis precipitated; after the removal of alcohol on the water-bath30 LEVY: THE ACTION OF AXINO-ACIbaddition of water causes the separation of an oil, which does notsolidify, even when cooled in a freezing mixture.The oil isextracted with ether, the ethereal solution dried, and the brownoil left after removal of the solvent fractionated under diminishedpressure. Ethyl maloiiate distils at 90-95O/ 12 mm. ; the tempera-ture then rises sharply, and a t 206-212O/12 mm. a yellow oildistils, a slight tarry residue remaining in the distilling flask. Onredistillation the oil passes over completely a t 206-207O/ 10 mm.,and is then obtained as a pale yellow, viscous liquid; the yield isalmost theoretical :0.2370 gave 0.4720 COB and 0.1550 H20.C=54*32; H=7.27.C1,H,,O,N requires C = 54.35 ; H = 7-32 per cent.The oil dissolves readily in cold concentrated sulphuric acid.When after keeping for a day the cold solution is poured on asmall quantity of ice, a white solid separates; from the ease withwhich this dissolves in water, and the reddish colour observed whenferric chloride is added to the aqueous solution, this was identifiedas the salt of the amino-acid; on diluting the filtrate, a yellow oilis precipitated. A clear solution is also obtained when ethyl alanyl-methylenemalonate is treated with cold concentrated hydrochloricacid; on diluting after one day, an oil separates, which has thed o u r of ethyl malonate. Decomposition also occurs when the esteris treated with three equivalents of cold alcoholic potassiumhydroxide, or with bromine in glacial acetic acid.Attempts were made to reduce the ester with the zinc-coppercouple. A solution in 95 per cent.alcohol was heated with thisreagent for two hours on the water-bath. After filtering, thealcohol wm removed by evaporation; the residue on addition ofwater formed an oil, which was extracted with ether, and found bydistillation to be the unchanged ester.Ethyl alanylmethylenemalonate does not react when treated withaniline in glacial acetic acid solution at the ordinary temperature;if the mixture is heated on the water-bath, decomposition occurs.No reaction occurs if a mixture of the ester with aniline alone isheated on the water-bath for two hours; but if this mixture is keptat 150° for the same time, a dark, oily product is obtained, whichsolidifies on cooling.The solid dissolves readily in warm alcohol;after boiling with animal charcoal, the filtered and concentratedsolution deposits on cooling a pale yellow solid, which is obtainedon crystallisation from dilute alcohol in elongated needles, meltinga t 118-119O:0.1910 gave 15.0 C.C. N, at 21° and 772 mm. N=9*08.This analysis and the melting point show the substance to be@lsH,80sNz requires N=9.03 per centESTERS ON ETHYL DICARBOXYGLUTACOWATE. 31the monoanilide of ethyl anilinomethylenemaZamte. The motherliquor on concentration yields a small quantity of malondianilide,arising, as in the action of aniline on ethyl aminomethylenemalon-ate (Ruhemann and Morrell, Eoc.cit.), from the further action ofaniline on the first substance.The monoanilide has also been recognised in the products of theaction of aniline on ethyl glycylmethylenemalonate and on ethyldimethylglycylmethylenemalonate (see below), and there can be nodoubt that the reaction is a general one for this series of compounds.Eth yE Dimet hylglyc ylmethylememalonat e,C0,Et. CMe,*NH*CH :C( C0,E t)2'This compound is obtained by the action of ethyl a-aminkso-butyrate hydrochloride on ethyl sodiodicarboxyglutaconate, themethod being the mme as that employed in the preparation of thealanyl derivative. The reaction in this case proceeds more slowly,however, and the yield is not quite so good. The oil distils a t220-222*/ 18 mm., with slight decomposition :0.1930 gave 0.3940 CO, and 0.1270 H,O. C =55*67; H= 7-31.C14HB06N requires C = 55-81 ; H= 7.64 per cent.E thtyl Ethylgl ycylmethylenemdonate,CO& t CEI E t -NH*CB: C( C0,E t)2.This compound, isomeric with the above, is prepared, in the sax138way, from ethyl a-aminobutyrate hydrochloride. It is a pale yellowoil, boiling at 214--215O/12 mm.:0.1820 gave 0.3720 CO, and 0.1240 H,O. C=55*74; H=7'57.C14H,,0,N requires C = 55.81 ; H'= 7.64 per cent.Bth yl Leuc ylmet h yl enemalonate,CHM%* CH( C 0,E t ) NH- CH C ( C02E t)*This substance, obtained from ethyl leucine hydrochloride bythe same method as the above, is a yellow oil distilling with slightdecomposition a t 233-234O/ 12 mm. :0.1680 gave 0.3590 COB and 0.1220 H,O. C=58*28; H=8*21.C,,H,,O,N requires C = 58-36 ; H= 8.21 per cent.In conclusim, I wish t o express my sincerest thanks t o Dr. 8.Ruhemann, who suggeeted to me this investigation, and has helpedme throughout by his kind advice.CAMBRIDGE.UNIVERSITY CHEMIUAL LABORATORY