梁晓天, 秦锡元, 毕六辰. 氮芥型化合物2-甲基-4-双-(2′-氯乙基)-氨甲基噻唑盐酸盐的合成J. 药学学报, 1959, 7(6): 218-221.
引用本文: 梁晓天, 秦锡元, 毕六辰. 氮芥型化合物2-甲基-4-双-(2′-氯乙基)-氨甲基噻唑盐酸盐的合成J. 药学学报, 1959, 7(6): 218-221.
Liang XIAO-TIAN QIN XI-YUAN BI LIU-CHEN, . THE SYNTHESIS OF 2-METHYL-4-BIS-(2'-CHLOROETHYL)-AMINOMETHYL-THIAZOLE HYDROCHLORIDEJ. Acta Pharmaceutica Sinica, 1959, 7(6): 218-221.
Citation: Liang XIAO-TIAN QIN XI-YUAN BI LIU-CHEN, . THE SYNTHESIS OF 2-METHYL-4-BIS-(2'-CHLOROETHYL)-AMINOMETHYL-THIAZOLE HYDROCHLORIDEJ. Acta Pharmaceutica Sinica, 1959, 7(6): 218-221.

氮芥型化合物2-甲基-4-双-(2′-氯乙基)-氨甲基噻唑盐酸盐的合成

THE SYNTHESIS OF 2-METHYL-4-BIS-(2'-CHLOROETHYL)-AMINOMETHYL-THIAZOLE HYDROCHLORIDE

  • 摘要: 本文证实了氰乙酸乙酯与硫化氢作用所得的反应液与1,3-二氯丙酮在无水乙醇中反应后,进行昇华,所得的产物是2-甲基-4-氯甲基噻唑盐酸盐。并由它合成了氮芥型化合物2-甲基-4-双-(2′-氯乙基)氨甲基噻唑盐酸盐,供作抗肿瘤的试验。

     

    Abstract: Ethyl cyanoacetate in ethyl alcohol (triethanolamine catalyst) was treated with hydrogen sulfide gas at 408—50° for 60 hours in order to get ethyl thiocarbamylacetate (Ⅰ). Treatment of the crude reaction mixture with 1, 3-dichloroacetone, however, gave 2-methyl-4-chloromethylthiazole hydrochloride (Ⅲ) instead of the expected ethyl 4-chloromethyl-2-thiazolylacetate (Ⅱ). It has been reported that ethyl thiocarbamylacetate (Ⅰ) reacted normally with α-halocarbonyl compounds to form thiazole derivatives. The method of preparation of Ⅰ in the literature cited consists of treatment of ethyl cyanoacetate in ether (triethylamine catalyst) with hydrogen sulfide at 65—70° for 2 hours. Probably our experimental condition was more strenuous so that Ⅰ suffered further decomposition giving thioacetamide as the result of hydrolysis and decarboxylation. The formation of Ⅲ from thioacetamide is straightforward. As part of a program on the study of physiologically active heterocycles, Ⅲ was treated with diethanolamine and then with thionyl chloride to give the nitrogen mustard, 2-methyl-4-bis-(2'-chloroethyl)-aminomethyl-thiazole hydrochloride (Ⅵ).

     

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