N-[(1-芳基-3-苯基-吡唑-4-基)次甲基]-2-羟基苯甲酰肼类衍生物的合成、表征及抑菌活性

Synthesis,Characterization and Antibacterial Activities of N-[(1-Aryl-3-phenyl-pyrazol-4-yl)methylene]-2- hydroxybenzohydrazide Derivatives

依据生物活性叠加原理,以邻羟苯基和苯基吡唑为分子核心,构建了6种未见报道的N-[(1-芳基-3-苯基-吡唑-4-基)次甲基]-2-羟基苯甲酰肼衍生物.以芳胺为原料,经重氮化、还原、与苯乙酮缩合及Vilsmeier-Haack反应制得1-芳基-3-苯基-4-甲酰基吡唑,再与水杨酰肼反应制得目标化合物,其结构经IR,1HNMR和元素分析等验证.探讨了制备中间体(3a～3f)的反应机理,结果表明,1位芳环上取代基对关环反应有显著影响,供电基有利于关环反应的进行,吸电基则恰恰相反.抗菌活性测试表明,质量分数为0.01%的化合物对大肠杆菌和白色念珠菌的抑菌率高达100%,有极强的抑菌活性,对金黄色葡萄球菌的抑菌率达70%以上,有一定的抑菌活性,是一类极具潜力的抗真菌和抗革兰氏阴性菌的化合物.构效分析结果表明,1位芳基中引入Cl和Br等卤原子,能显著增强化合物的抑菌活性,而引入NO2和CH3基团,则会降低其抑菌活性.

A series of novel N-[（1-aryl-3-phenyl-pyrazol-4-yl）methylene]-2-hydroxybenzohydrazide derivatives were designed and synthesized by combining o-hydroxyl phenyl and phenyl pyrazole with hydrazone bond,according to the superposition principle of biological activities.Six compounds are all novel.Substituted aniline was diazotized and subsequently reduced to give substituted phenylhydrazine,acetophenone arylhydrazone were obtained by the condensation of acetophenone with substituted phenylhydrazine.1-Aryl-3-phenyl-4-formylpyrazoles were obtained with N,N-dimethylformamide and phosphorus oxychloride,which was reacted with salicylic hydrazide to get the title compounds.The structures of all title compounds were confirmed by ^1H NMR,IR and elemental analysis.The reaction mechanism of acquiring 3a—3f show that catalytic reaction activity is enhanced by electron-donating groups of the first phenyl ring,but reduced by electron-withdrawing groups of the first phenyl rings.The result of preliminary bioassay show that the inhibitory rate against Monilia albican and Escherichia coli of the title compounds can be high to 100% at 0.01% mass fraction,inhibitory rate against Staphlococcus aureus is over 70%.They will be a series of potential antibacterial compounds against fungi and gram-negative bacteria.The analysis of structure-activity relationship show that the antibacterial activities of title compounds are enhanced by the halogen groups of the phenyl ring,but reduced by electron-donating and electron-withdrawing groups of the phenyl ring,such as NO2 and CH3.