3214
Vol. i(i
NOTES
1-Nethylhydantoin,' which had been synthesized 50 cc. of absolute methanol was cooled iii i t i i ice-bath aiit1 from sarcosine (M-methylglycine) a n d potassium saturated w i t h hydrogen- chloride. The mixture w a s Alowed to-remain- a t room temperature- whereupon the acid cyanate, was condensed with indole-3-aldehyde2to slowly dissolved. By slow evaporation of the solvent from forni 1-inethyl-5-(3'-indolal) -hydantoin.' This hy- the solution, under reduced pressure in a desiccator which dantoin had been heated with ammonium sulfide in contained calcium chloride, a crystalline residue \vas obtained. It was covered with methanol aut1 the solvent \v:t\ a sealed tube a t 100" for 3 days, by Miller and Rob- removed in t h e manner just described. If necessary, this son,l in order to reduce it to l-methyl-5-(3'-indo- process was repeated in order t o remove the odor of hydrolylinethyl] -hyd-antoin. ne found- that this reduc- gen chloride. The hydrochloride, which was slightly contion could be carried out a t 40-50" by the use of taminated by a light violet impurity, nielted a t 185-188". ilnal. Calcd. for C13Hii02XZCl: N, 10.42: CI, 13.20. Raney nickel, and could be completed in 5-6 hours. &h'en the last-mentioned hydantoin was refluxed Found: N, 10.41; C1, 13.56. The finely powdered hydrochloride was suspeiitletl in abwith barium hydroxide, according to the directions solute ether, t h e mixture was cooled and saturated with dry, in the literature, a-methylamino-/3-(3-indolyl)-pro-gaseous ammonia. After 10 minutes, thc mixture 1va5 pionic acid was obtained. We converted this acid filtered through a sintered glass funnel and the solvent 1va5 into the methyl ester hydrochloride, in quantita- removed from the filtrate in the manner described above; tive- yield; by the use of methanol and hydrogen the residue, t h e ester base, melted a t 70-72"; yield 2.3 g. chloride. T h e ester base was formed when the (45%). Anal. Calcd. for CljH:;OeX~: C, 67.21; 11, (!.%; S, salt was treated with ammonia. 12.06. Found: C, 67.34; H, 6.84; N, 12.28. I t was discovered that sarcosine could be preThe picrate was obtained when the cstcr was treatctl w i t h p a r d by a much simpler method than t h a t which an alcoholic solution of picric acid; m.p. 180-182O. The hydrobrornide precipitated when a n ethereal solutioil has been dcscribedl3namely, by interaction of chloof the ester was treated with hydrogen broinidc; m . p . 163roacetic acid and methylamine. 165" after recrystallization from absolutc ethanol-ether. Experimental COLLEGEOF PHARMACY CSIVERSITY O F %CIIIGAX Sarcosine.-Two liters of 30% aqueous methylaniine \vas stirred and 47.5 g. of chloroacetic acid, dissolved in 30 cc. of Asx ARBOR,hIICIlIG.4S water, was added slowly. After 24 huurs, t h e swlutim- w a concentrated under reduced pressure t o a thick sirup which \vas diluted with absolute ethanol until the volume was The Preparation of 2-Disubstituted Amino-5,5-diabout 210 cc. The alcoholic solutio11 was then kept a t phenyl-4(5H)-imidazolonesI about -10" for 13 hours, the crystalline precipitate wa5 removed by filtration and the filtrate was diluted with abBY C. E;. CAINAYD SARAI(. SAEGELE solute ethanol until the volume mas about 225 cc. h;hen RECEIVED DECEMBER 4, 19% the solution was cooled t o -lo", and maintained at t h a t temperature, more crystalline material deposited. The In spite of the large number of 5,3-disubstitutetl combined precipitates were recrystallized twice from 95% hydantoiris which have been prepared and studied ethanol; m.p. 212-215°,4 yield 18.0 g. (40.5%). l-Methy1-5-(3'-indolylmethyl)-hydantoin.-Five grains pharmacologically, the corresponding 2-imino coliiof activated Raney nickel5 was added t o a mixture of 5.0 g. pounds (glycocyaniidines) have received little of l-metliyl-5-(3'-indolal)-hpdantoin1 and 100 cc. of 1 A: attention. Recently Hoffniann2reported the prepsotliuin hydroxide solution. The mixture was hydrogenated aration of 3,3-diphenyl-2-iminohydantoin(5,sa t 10-50° under :in initial pressure of 40 pounds. After coiiii~letetlrctluctioii (5-6 hours), the catalyst was removed diphenylglycocyainidine) (formula I) aiid Deliwala !>y filtratioii aiic! :he filtrate :va.;at(!jus,tcd t o a pE of 6.5 ~ v i t ! ~ and iiajagopaiari' described the synrhesis of- a few 1 : I hytlrochloric acid. T h e product, which separnted related compounds. No examples could be found froiii the cooled mixture, \veighecl 4.5 g. (90%); m.1). 2132113O.6
~Methylamino-~-(3-indolyl)-propionic Acid.7-This suhstance was obtained by treatment of l-methyl-5-(3'i n t l o l ~ - l i n e t h ~ - l ) - l i ~ - d a ~with ~ t o i barium n hydroxide solution by the procedure of Miller and Robson'in 8070 yield; m . p . 272-375" ~ I e c . ~ A d . C d c d . for CI2HlaO2S2:C, 65.53; H, 6.46. Fuund: C, 65.19; H, 6.63. T h e hydrochloride, prepared according t o t h e directioiis ill the literature,' melted at 220-222D.9 Thc picrate, prepared by a described method,'O melted a t 185-186O dec." Methyl ~-Methylamino-~-(3-indolyl)-propionate and Hydrochloride.--A mixture of 5.0 g. of the propionic acid and _.
E. J . l f i l l e r and W. R o b a o n , J . Cheirz. S O L . 1910 , (1938). J Elks, D. IT, Elliot and B. A . Hems, ibid., 029.(191.1). U'. Cocker, i b i i l . . 1693 (1937). Reference 3, m . p . 211-212°. A. A , Pavlic and H. Adkins, THIS J O U R N A L , 68, 1171 (19.16). ( 6 ) Reference 1, m.p. 211-212'. fl) (2j (B) (-I) (31
(T) The name N-methyltryptophan, which has been used for this compound, is an unsatisfactory one as has been pointed out by hliller and Rson.' ( 8 ) Relerence 1, m 1). 2-13'; \V. G. Gordon and l < , \V Jncksrln (.I 14iol. C h e ~ z . 110, , 1.74 (1935)), in 1). 2 ! ! 7 O rlrc. (9) Itefcrence 1, m.p. 192-193'; N. Ghatak (Buil Actrd SCi C'iziled Pvouinces.Agrn O z l d k , India, 3, 295 (1934); C . A . , 29, 33-11 (1933)), m.p. 221-222'. f l n ) \\'. If.Cahill and R. W.Jackson, J Gir~lCiicibi , 126, 20 (1938). 1 1 I i?Lr,.r,,,lcc, li!, ~n 11 lS.i-lRI;o d c r
in the literature of compounds containing a disubstituted amino group attached to the carbo11 atom between the two nitrogen atoins of the ring (formula 11). Such a structure is of interest since the existence of the tautomeric forni involving a double bond between carbon atom 2 and the cxocyclic atom attached to it is not possible, at lcast in neutral or basic medium. H O=C-- --SH
I
o=c-..-
h-
I1
Several 2-disubstituted aiiiino-5,3-dipheiiyl-~(5~~ j iiiiidazolones have been prepared in good yields by the reaction of 2-rnethylinercapto-5,3-diphenq.l4(5H)-imidazolone with an excess of R secondary amine (Table I ) . Diisopropylalnilic failed to give any detectable reaction under thc coiitlitions tried. ( 1 ) I'resentetl lieiiire t h e l)ivisi
