1，2，4-三唑类化合物的合成及其活性预报

【作者】 舒绪刚；

【导师】 黄慧民； 李大光；

【作者基本信息】 广东工业大学 ， 化学工艺， 2002， 硕士

【摘要】 探索杂环化合物的合成及生物活性是有机化学中最具生命力的研究课题之一。在现有众多杂环化合物中，1，2，4-三唑类衍生物由于其广谱的生物活性及其广阔的应用前景一直颇受人们的青睐。 本文在总结前人研究的基础上，合成了化合物3—氨基—1，2，4—三唑、3-硫醇-5-氨基-(1H)-1，2，4-三唑、均三溴甲基苯和1，3，5—三(5-氨基-(1H)-1，2，4-三唑-3琉基甲基)甲苯等三唑类化合物，对其中每一种化合物的合成路线做了对比，选择其中较优工艺进行研究，并对部分工艺作了改进研究，最后用分子连接性指数对所合成的化合物的生物活性做了预报。 1．在前人合成3—氨基—1，2，4—三唑路线的基础上，笔者运用化学平衡原理，对工艺进行改进，大大提高了产物的得率。同时产物纯度也得到提高。另外，对改进后的工艺作了一些研究，得到最优化条件为：氨基胍盐:甲酸=1:1.04，带水剂用二甲苯，反应后期加二甲基苯胺调节PH值12左右，反应时间5—6小时，产率可达97％。 2．总结了3-巯基-5-氨基-(1H)-1，2，4-三唑的五种合成方法，通过对比找其中最有工业化前景的方法，随后用正交优化方法进行了工艺研究，得到最佳工艺为：1:1.25mol比的氨基胍(盐)与二硫化碳原料，在无水乙醇—乙酸溶液中，并在三乙胺存在下，回流反应7h，可得68％以上的ATZ。并用氨基胍盐和硫脲作原料用微波合成，该法缩短了反应时间短，产率高，温度低。 3 合成了1，3，5—三(5-氨基-(1H)-1，2，4-三唑-3巯基甲基)甲苯，并对其中间体1，3，5-三溴甲基苯的合成做了研究，得到优化条件。 4．引用实例对比了两种分子连接指数在含预报氮杂环化合物中的应用，并用朱龙观等提出的分子连接性指数对所合成的几个化合物进行了活性预报。更多还原

【Abstract】 Studying the synthesis of heterocyclic compounds and their biologic activity is one of most spirited items in organic chemisty. 1,2,4-triazole is fascinating in multitudinous heterocyclic by virtue of their activity and excellent potentialThis thesis was on basis of former research work .several compounds was synthesized which comprise 3-amino-l,2,4-triazole,3-mercapto-5-amino-1,2,4-trizaole, 1,3,5-tri(brommethyl)benzol, 1,3,5-tri(5-amino-1,2,4-triazo le-3-mercaptomethyl)benzene.the synthesized process of each compounds was reviewed and and study some of them in order to attain a better process. Finally.the activity of the synthesis compounds was forescasted by molar connective index1.A improve synthesis process which applied chemistry balance principle and employed entraining agents was brought out on basis of the former research work.the method was noticeable increase yield and the pure degree. What’s more ,effects on the synthesis was done ,attaining the optimum conditions that molar ratio of aminoguanidine bicarbonate to formic acid is 1:1.04, the overall reaction time is 5~6h, xylene was used as entraining agents.Under the optimum condition,the yield of 3-amnio-l,2,4-triazole is 97%(calculated on the basis of pure aminoguanidine bicarbonate2.review the five synthesis methods for 3-mercapto-5-amino-(lH)-l,2,4-triazole.then we study the most applied promising method making use of crossing experimentunder the fitting condition ,the yield is 68%,which is higher than values reported by national periodicals.besides,we synthesized the object product by microwave radiation which has higher yield and shorter reaction time and less pollution3.the synthesized of l,3,5-tri(5-amino-3-mercaptomethyl)benzene and 1,3,5-tribrommethylbenzene was studied.the effect of reaction time,reaction temperature,and molar ratio of starting materials on the yield for the 1,3,5-tribrommethylbenzene was-II-discussed,under the conditions of molar ratio l,3,5-trimethyibenzene:NBS=l:3.15,temperature 60,reaction time 1 Oh, initiator 0.1 g.the yield was 25%.4.correlations have been derived for prediction of toxicity to ciliate.indicated in logBR for heterocompound from molecular connectivity index.the index can be easily caculated solely from molecular structure of the chemicals.the correlation contains two variables and predicts the activity for these heterocompounds,we made use of it predict three compounds which we synthesized.更多还原