1,3,4-噁二唑-2-硫酮衍生物的合成及工艺

噁二唑类化合物是一类具有广泛生物活性的杂环化合物,具有高效,低毒等优点.设计合成了4a~4g 7个1,3,4-噁二唑-2-硫酮衍生物并经过核磁共振氢谱和质谱进行结构表征和确认.以苯甲酸甲酯(1)为起始原料与水合肼加热回流反应得到苯甲酰肼(2),然后与二硫化碳在碱性条件下回流合环生成中间体5-苯基-1,3,4-噁二唑-2-硫酮(3),最后与一系列取代苯胺和甲醛发生曼尼希反应得到目标化合物.实验过程中对反应(a)中反应时间和80%水合肼与苯甲酸甲酯(1)的摩尔比,反应(b)中反应时间和二硫化碳与苯甲酰肼的摩尔比,反应(c)中溶剂的选用等参数进行了工艺优化.以适当溶剂重结晶均得到纯的目标化合物,收率在20%~80%.大部分目标化合物是未见文献报道的新化合物,其作为酪氨酸酶抑制剂的生物活性有待进一步研究.

Synthesis of 1,3,4-oxadiazole-2-thione derivatives

Oxadiazole derivatives as heterocyclic compounds have shown a broad range of biological activities.Seven 1,3,4-oxadiazole-2-thione derivatives were designed and synthesized,and all of them were characterized and confirmed by 1 H NMR and mass spectrometry.Benzoyl hydrazine （2） was obtained by the reaction of benzoate methyl ester （1） and hydrazine hydrate under refluxing,then 5-phenyl-1,3,4-oxadiazole-2-thione （3） was obtained by the reaction of benzoyl hydrazine （2） and CS2 in alkaline condition under reflux.Finally target compounds were obtained by Mannich reaction consisting of （3） condensation with amine in the presence of formaldehyde.In the process,the technology is optimized based on some parameters：reaction time,molar ratio of 80 ％ hydrazine hydrate and benzoate methyl ester （1）,molar ratio of CS2 and benzoyl hydrazine （2） in reaction （a） and （b） respectively,the use of solvent in reaction （c）.Pure target compounds were obtained by recrystallization from suitable solvent,the yields of which were between 20％-80％.Most of the compounds haven＇t been reported yet,and their bioactivities as tyrosinase inhibitors remain further study.