Tvhich, after removal of the exwss tiiazoniethane a ~ i dthe solvetit, was obtained as a light yellow liquid (5 g . ) . The crude ester was allowed to react overnight a t room temperature with chloroacetic anhydride (4.5 g.) in benzene solution. The reaction mixture was warmed on a steam-cone for an hour and then the solvent \vas removed. On pouring the residue into water and stirring, crystals (5.95 g., 83.2%), rn.p. 92-100", separatcd. Ry rccrystallization from a mixture of benzene and ligroin, the amide was obtaincrl as colorless, stout prisms (5.6 g., 94yoj, m.p. 95-98'. After further recrystallization from ligroin, the m.p.was constant L ' t M6.972. .-I~zn/. Calcd. for CIIKI~O.ISCIS: C, 52.09; H , 4.71; S.4 , t j i . Found: C , 52.24; 11, 4.84; S , 4.75.
Both the crystalline and liquid fractions were optically 'ictive, the specific rotations in alcohol, [ a ] 2 5 were ~ -20.7" .ind +28.2 O , respectively. In another experiment using 6 g. of D-penicillamine methyl ester hydrochloride, the undistilled reaction mixture was seeded. After two days in a refrigerator, 3.3 g. (37.3%) of crystalline product, m.p. 43-45', was obtained.
2-Carbethoxy-3-benzoyl-4-carbomethoxy-5,5-dimethyl-
thiazolidim-To it suspension of 2-carbethoxy-4-carbo. tiiethoxy-5,j-diniethylthiazolidiiie (0.5 8.) in 10% sodium hydroxide solution was added benzoyl chloride (0.25 nil. ) v i t h vigorous shaking. After one hour, the reaction misture \vas warinzti on a steam-cone to destroy excess benzoyl chloride and \vas then extracted with ether. The dried !~odiuin sulfate) ethereal solutioti \vas conceiitrated to 311 2-Phenyl-3-chloroacetyl-4-carbomethoxythiazolidinesul-oil which \viis purified by a n evaporative distillatioii ( 1Yll foxide. (a).-A solution of I11 (1.2 g . ) in dioxane (15 ml.! 140° (0.5 inin. ) ) ; a colorless and very viscous oil (0.27 g. was treated with potassium permanganate (0.17 g . ) dis3 8 % ) was obtained, The infrared spectrum has an amid< solved in glacial acetic acid ( 5 in].). After one hour the band a t fj.02 p in atiditioti to the ccirhonyl b m d (:idouble reaction mixture was decolorized by the addition of a few peak at 5 . 2 a ~ i t l5.77p ) . drops of hydrogen peroxide. B y pouring the colorless solud n a l . Calcd. for ClrH?lO&S: C, 58.10; €I, fi.02; S , tion into water 0.54 g. of crystalline material was obtained. 3.99. Found: C , 57.95; H, 6.02; S . 3.86. This was washed with ether to remove the starting material 2-Carbethoxy-3-chloroacetyl-4-carbomethoxy-5,5-dimetharid then crystallized thrice from ethanol and twice fro? ylthiazolidine ( Ij , ~--A mixture of 2-earbethoxy-4-carbochloroform--ether. The m . p . was constant at 211--218 methoxy-3,5-dirnethylthiazolidine(0.8 9 , ) and chloroacetic (tlec. 1. anhydride ( 1 g . i was kept overiiight at 70-7.5". T h r etheril nal. Calcd. for C I ~ H I J O & C eal extract o f the melt was washed successively with water, S,4.44. Found: C,49.:31; H , 4 . dilute hydrochloric acid, water, sodium bicarbonate SOIU( b ).--To a solution of 111 ( 1 . 5 9.) in acetic acid was added tion and water. The tlried ethereal solution gave a reddish 1.5 ml. of 35% hydrogen peroxide. After two weeks the brown oil (0.88 g . ) after concentration. A faintly yellow solution was poured into water, 1.26 g. of crystalline mate:md very viscous oil (0.77 g., 73.6%) rvas obtained by an rial, yield 79.670, m.p. 195-205', was obtained. oRecrys- evaporative distillation (130-140' (0.5 m m . j ) . A colorless tallization from ethanol raised the m.p. to 210-212 . analytical sample was prepared by two more evaporative S o reaction was observed when a solution of the sulfoxide distillations. in dry dioxane was treated with triethylamine. Anal. Calcd. for C12HlxOaNClS: C, 41.52; H , 5 . N ; 2,4-Dicarbethoxythiazolidine(IV).-Cysteine ethyl ester A', 4.33. Found: C, 44.66; H , Z.68; S ,4.13. hydrochloride (4.2 g.) and sodium acetate (2.7 g.) were dissolved in 20 ml. of water. Ethyl glyoxalate alcoholate OF CHEMISTRY DEPARTMEKT (3.35 g . ) in 80 ml. of alcohol was added and the reaction MASSACHUSETTS IXSTITUTE OF TECHNOLOGY mixture was stored for two days. After removal of most CAMBRIDGE 39, h4ASSACHUSETTS of the alcohol by distillation, the oily layer which separated \vas collected in ether. The dried (sodium sulfate) ether extract was concentrated to ii yellow liquid (4.5 g.). By evaporative distillation 2.8 g. (53%) of the thiazolidine was obtained. An analytical sample, n2% 1.4880, d2jr 1.1991, The Reaction of Azomethines with Methylmagw:is prepared by a second evaporative distillation. nesium Iodide' .4nnl. Calcd. for CSHlj04SS: C , 46 B Y PAUL &I. MACINNITY AND THOMAS J. GAIR . Foiind: C, 4fi.57; M K , 56.03. RECEIVEDAPRIL11, 1952
2,4-Dicarbethoxy-3-chloroacetylthiazolidine (VI) .-A
The classical investigations of Busch2 and his coworkers indicated that Schiff bases reacted with the Grignard reagent in a manner analogous to aldehydes, but only one example involving a keto ani1 was reported. Such reactions were used by subsequent workers, notably Moffett and HoehnI3and Campbell and co-workers4 to prepare substituted aromatic secondary amines, but the problem of isolating the intermediate Grignard addition compound and determining its composition was not 2-Carbethoxy-4-carbomethoxy-5,5-dimethylthiazolidinestudied. (V).--To a solution of I)-penicillamine methyl ester hydroSachs and Sachsj attempted the isolation of the chloride ( 8 g . ) a r i d sodium acetate (2 g . ) in 20 inl. of water compounds resulting from the action of phenylrnagw a s added ethyl glyoxalate :rlcoholate (2.8 g , ) in 50 ml. of nesium bromide and ethylmagnesium bromide on alcohol. After two days the alcohol was removed, leaving oily droplpts in a n aqueous suspeiisioii. The oil was col- quinoline in ethyl ether. Their analyses indicated lected with ether, Trashed, and thc dried ethereal solution that one mole of the organomagnesium compound was concentrated to a pale yellow liquid (3.71 6.1.An and one mole of quinoline had reacted, although the mixture of 11. (0.87 g . ) arid chloroacetic anhydride (0.8 g. j x i s allowcd to react overnight at 60--70'. The reaction mixture was then poured into Ivater and extracted with cther. The ether extract was washed successively with sodium bicarbonate solution arid water. Removal of ether dried (sodium sulfate) solution left a slightly yelOLE oil (1.15 g . , 81701. Evaporative distillation O ( 0 . 4 n i n i , ) ) gave a colorless, viscous oil (90% recovery). A secoiitl e\Taporative distillation afforricd 311 :inalytical s:iniple, n% 1.5090. A n d . Calcd. for ClIITlbOhC1NS: C, 42.65; I€,
