Synthesis Of 1,5- Benzodiazepines And The Research Of Their Antimicrobial Activities

1,5- benzodiazepines are a kind of seven-membered heterocycle compounds and have both important physiological activities and biological activities. They are commonly used as medication which has the curative effect of treatment nervous system and cardiovascular system diseases. In addition this kind of compounds also has effect of antifungal, antimicrobial, antivirus and antagonist. So far 1,5- benzodiazepines has got a huge applications in medical treatment and the effect is good. Therefore the research of its unique chemical structure and special physiological activity has been getting people's attention.The research showed that the ester and carboxyl which in the different places of seven-membered heterocycle are active groups, also they can effectively increase the antimicrobial activity. In order to find new 1,5- benzodiazepine compounds which have efficient antimicrobial activity, seven 2-alkoxyl carbonyl-4-aryl-1,5- benzodiazepines derivatives and four 4-aryl-1,5-benzodiazepines-2-formic acid derivatives are designed and synthesized in this paper. We have tested the antimicrobial activities of all these 1,5- benzodiazepines and their structure- activity relationship has preliminary researched for the foundation of further research. The reaction was researched exhaustive and the best conditions and surmised mechanism of the reaction was chose.This thesis includes the following parts:Firstly, four 4-aryl-1,5-benzodiazepines-2-formic acid derivatives are synthesized by the Friede-Crafts acylation reaction, aza-Michael addition reaction and cyclo-addition reaction, where different substituted benzene is used for the raw materials, and the structures of these new compounds are determined by IR,1H NMR and MS method. The exhaustive research on the synthesis reaction of the class of compounds was carried out in this paper.Secondly, seven 2-alkoxyl carbonyl-4-aryl-1,5- benzodiazepines derivatives are synthesized by the Friede-Crafts acylation reaction, esterification reaction, Michael addition reaction and cyclo- addition reaction, where different substituted benzene is used for the raw materials, and the structures of these new compounds are determined by IR,1H NMR,13C NMR,and MS method. The reaction mechanism has been unequivocally established in this paper.Thirdly, the reaction condition on the synthesis of 2-alkoxyl carbonyl-4-aryl-1,5-benzodiazepines derivatives and the reaction selectivity are studied exhaustive and the best reaction conditions was obtained.Lastly, antimicrobial activities of these novel compounds are studied in vitro by filter paper method. Based on these results, structure-activity relationship is preliminary established and their antimicrobial activities was compared with 1,5- benzodiazepines which was synthesized by our group.