苯酚取代基4-氨基-1,2,4-三氮唑-3-硫醚的合成及其抑菌活性

Synthesis and Anti-Bacterial Activities of Phenol Substituted 4-Amino-1,2,4-Triazole Thioethers

摘要: 以5-(2-苯酚)-4-氨基-1,2,4-三氮唑-3-硫醇为原料，室温下在碱性水溶液中与卤代烃进行醚化反应得到3个苯酚取代基4-氨基-1,2,4-三氮唑-3-硫醚化合物，其结构通过¹H NMR、¹³C NMR、MS、IR、元素分析及单晶X-射线衍射等进行表征，采用倍比稀释法来测定中间体及3个目标产物化合物对金黄葡萄球菌、白色念珠菌、枯草芽孢杆菌、大肠杆菌的抑制活性。晶体结构测试结果表明：化合物1和2a均存在分子内氢键，相邻分子之间主要通过氢键发生相互作用，硫醇结构变为硫醚结构后1,2,4-三氮唑五元环会发生翻转。抑菌活性测试结果表明：化合物1和2c在测试浓度范围内对白色念珠菌均有较好的抑菌活性，化合物1对金黄葡萄球菌的MIC值为500 μg/mL，化合物2c对大肠杆菌的MIC值为500μg/mL，而化合物2a和2b对供试菌种均无抑菌活性。

Abstract: Three phenol substituted 4-amino-1,2,4-triazole-3-thioethers were synthesized by etherification reaction of 2-(4-amino-5-mercapto-4H-1,2,4-triazol-3-yl)phenol with halohydrocarbon in alkaline aqueous solution under room temperature, and characterized by ¹H NMR, ¹³C NMR, IR, elemental analysis, and single-crystal X-ray diffraction, and then the inhibitory activity of compound 1 and 2a~2c against Escherichia coli, Candida albican, Staphyloccocus aureus and Bacillus subtilis were achieved by dilution doubling method. The experiment result of single-crystal X-ray diffraction revealed that both compound 1 and 2a have intramolecular hydrogen bonds, the neighbouring molecules interact mainly through hydrogen bonds, and the 1,2,4-triazole five-membered ring reverses when the thiol structure changes to a thioether structure. The result of anti-bacterial ac-tivities showed that both compounds 1 and 2c had good bacteriostatic activity against Candida al-bican within the test concentration rage, the MIC value of compound 1 for Staphyloccocus aureus was 500 μg/mL, and the MIC value of compound 2c on Escherichia coli was 500 μg/mL, while Compounds 2a and 2b had no antibacterial activity on the four tested strains.