3-(N-取代苯基-2-乙酰胺基)硫基-4-N-取代邻羟苯基亚胺基-5-甲基-1,2,4-三唑类化合物的合成及生物活性研究

以对称二氨基硫脲为原料,与冰醋酸反应生成5-甲基-4-氨基-1,2,4-三唑-3-硫酮(1);在弱酸性条件下,1与取代水杨醛反应生成席夫碱中间体5-甲基-4-(N-取代邻羟苯基)亚胺基-1,2,4-三唑-3-硫酮(2a～2c);最后在碱性条件下分别与N-取代苯基-2-氯乙酰胺发生烷基化反应生成15种未见报道的目标化合物3-(N-取代苯基-2-乙酰胺基)硫基-4-(N-取代邻羟苯基)亚胺基-5-甲基-1,2,4-三唑(3a～3o),其结构经IR,1H NMR,13C NMR确证.初步生物测试表明,质量分数为0.01%时,3a～3o对白色念珠菌的抑菌率均达90%以上,具有很强的抑菌活性;对金黄色葡萄球菌、大肠杆菌的抑菌率达80%以上,具有较强的抑菌活性.

Synthesis and Biological Activities of 3-(N-Substituted-phenyl-2- acetamido)-sulfur-4-(N-substituted-2-hydroxyphenyl)i mino5-methyl-1,2,4-triazoles

Firstly,5-methyl-4-amino-1,2,4-triazole(1) was obtained by a cyclization reaction of glacial acetic acid with thio-phenyl-2-acetamide under alkaline conditions.The structures of all compounds have been confirmed by IR,1H NMR and 13C carbohydrazide.In weak acidic conditions,the Schiff base 5-methyl-4-(N-substituted-2-hydroxyphenyl)imino-1,2,4-triazole-3-thione(2a～2c) was obtained by the reaction of compound 1 with substituted salicyladehyde.Finally,the title compounds 3-(N-substitutedphenyl-2-acetamido)sulfur-4-(N-substituted-2-hydroxyphenyl)imino-5-methyl-1,2,4-triazoles(3a～3o) which have never been reported were synthesized by nucleophilic substitution reaction of compound 2 with N-substituted NMR spectra.The results of preliminary bioassay showed that,at the mass concentration of 0.01%,compounds 3a～3o have more than 90% inhibitory rate against Monilia albican,which displayed excellent bacterial activities.Meanwhile,the title compounds also have more than 80% inhibitory ratio against Staphylococcus aureus and Escherichia coli.