1-对甲苯基-5-取代苯基亚胺基-1,2,3-三唑甲酸/甲酰胺的合成及生物活性研究

Synthesis and Biological Activities of 1-(4-Methyl)phenyl-5-sub-stituted phenylimino-1,2,3-triazole Carboxylic Acid/Caboxylic Acid Amide

以对甲基苯胺为原料,经过重氮化反应生成对甲基叠氮苯(1).在强碱性条件下,1分别与氰基乙酸乙酯、氰基乙酰胺反应,制得中间体1-对甲苯基-5-氨基-1,2,3-三唑甲酸乙酯(2)和1-对甲苯基-5-氨基-1,2,3-三唑甲酰胺(5);中间体2经水解生成1-对甲苯基-5-氨基-1,2,3-三唑甲酸(3),进而在弱酸性条件下与取代苯甲醛反应得到6个未见文献报道的目标化合物1-对甲苯基-5-取代苯基亚胺基-1,2,3-三唑甲酸(4a～4f),5与取代苯甲醛反应得到6个未见文献报道的目标化合物1-对甲苯基-5-取代苯基亚胺基-1,2,3-三唑甲酰胺(6a～6f),化合物的结构均经IR,1H NMR,13C NMR确证.初步生物测试表明,12个化合物均表现出良好的抑菌活性,其中化合物4d～4f和6d～6f对金黄色葡萄球菌、白色念球菌的最小抑菌浓度(MIC)值为2～8μg/mL,抗菌效果优于氟康唑和三氯生.

4-Methylphenylazide （1） was synthesized through diazotization reactions from 4-methylaniline, and then reacted with ethyl cyanoacetate or 2-cyano-acetamide to obtain 1-（4-methyl）phenyl-5-amino-l,2,3-triazole carboxylic ethyl ester （2） and 1-（4-methyl）phenyl-5-amino-l,2,3-triazole carboxylic acid amide （5） in strong alkaline condition. Compound 2 hydro- lyzed into 1-（4-methyl）phenyl-5-amino-l,2,3-triazole carboxylic acid （3）. Then, in weak acidic condition, 1-（4-methyl） phenyl-5-substituted phenylimino-l,2,3-triazole carboxylic acids （4a^4f） were obtained from compound 3 and substituted benzaldehyde. Meanwhile, other 6 novel 1-（4-methyl）phenyl-5-substituted phenylimino-l,2,3-triazole carboxylic acid amides （6a-6f） were synthesized from compound 5 and substituted benzaldehyde. The structures of all compounds have been con- finned by 1H NMR, 13C NMR and IR. The preliminary bioassay showed that, all target compounds possessed efficient anti- bacterial activities. Especially, the mic values of compounds 4d-4f and 6d-6f were 2-8 μg/mL, lower than fluconazole and triclosan.