N-取代苯甲酰基-N′-4,7-二甲氧基-[1,2,4]三唑并[1,5-c]嘧啶(硫)脲的设计、合成及生物活性研究

Design,Synthesis and Biological Activities Evaluation of N-(Substitutedbenzoyl)-N'-4,7-dimethoxy-[1,2,4]-triazolo[1,5-c]pyrimidine(Thio)ureas

以α-甲氧基乙酸甲酯、甲酸乙酯和取代苯甲酸为起始原料,经过环化、Dimroth重排和亲核加成等反应,合成了一系列结构新颖的N-取代苯甲酰基-N′-4,7-二甲氧基-[1,2,4]三唑并[1,5-c]嘧啶(硫)脲类化合物11a^11q.目标化合物的结构通过IR、1 H NMR、13C NMR和元素分析进行了确认.初步生物活性测试结果表明,在50 mg·L^-1下,大部分化合物具有一定的杀菌活性,其中N-(2-氯苯甲酰基)-N′-4,7-二甲氧基-[1,2,4]三唑并[1,5-c]嘧啶硫脲(11m)对黄瓜灰霉菌的抑制率为67.25%.化合物均对2~3龄库蚊幼虫表现一定的昆虫生长调节活性,7个化合物的校正未羽化率高于70%,其中N-(4-甲基苯甲酰基)-N'-4,7-二甲氧基-[1,2,4]三唑并[1,5-c]嘧啶硫脲(11l)的校正未化蛹率和校正未羽化率均达100%,与对照药剂5%(质量分数)吡丙醚乳液相当.构效关系研究表明,苯环上吸电子基团的引入有利于杀菌活性的提高,而给电子基团的引入则有利于昆虫生长调节活性的提高.苯甲酰基脲类化合物11a^11i的杀菌活性普遍优于苯甲酰基硫脲类化合物11j^11q,而苯甲酰基硫脲类化合物则表现出更好的昆虫生长调节活性.

A series of novel N-(substitutedbenzoyl)-N'-4,7-dimethoxy-[1,2,4]triazolo[1,5-c]pyrimidine(thio)ureas(11a^11q)were synthesized fromα-methoxyl methyl acetate,ethyl formate and substituted benzoic acids by cyclization,Dimroth rearrangement and nucleophilic addition reactions.The structures of products were confirmed by IR,1 H NMR,13C NMR and elemental analysis.The preliminary bioassay showed that most of the compounds displayed positive fungicidal activity at 50 mg·L^-1.Among them,N-(2-chlorobenzoyl)-N'-4,7-dimethoxy-[1,2,4]triazolo[1,5-c]pyrimidinethiourea(11m)exhibited an inhibition rate of 67.25%against B.cinerea.All compounds showed certain insect growth regulation activities against 2~3 instar culex larvae,in which seven compounds exhibited revised uneclosion rate higher than 70%.N-(4-methylbenzoyl)-N'-4,7-dimethoxy-[1,2,4]triazolo[1,5-c]pyrimidinethiourea(11l)showed excellent insecticidal activity,which was equivalent to the control 5%(mass fraction)pyriproxyfen.The preliminary structure-activity relationship analysis showed that compounds with electron-withdrawing group on the phenyl ring showed higher fungicidal activities,while compounds with electron-donating group exhibited higher insect growth regulation activities.Benzoylureas displayed higher fungicidal activities and benzoylthioureas exhibited good insect growth regulation activities.