甲氧头孢中间体7-mac的合成工艺分析-analysis of synthesis technology of methoxycef intermediate 7 - mac.docxVIP

三峡大学硕士学位论文 三 峡 大 学 硕 士 学 位 论 文 PAGE PAGE VI Abstract 7α-methoxy cephalosporins cefoxitin, cefmetazole, cefotetan, cefbuperazone and cefminox have a strong antibacterial effect to Gram-negative bacteria and have a high degree nature of anti- β-lactamase. Mainly used of clinical treatment of pneumonia, bronchitis, biliary tract infections, peritonitis, endocarditis, pyelonephritis and other various types of inflammation. These drugs have broad market prospects, and 7-MAC(7β-amino-7α-methoxy-3-(1-methyl-1H-tetrazol-5-methylthio)-3-cephalospor inallyl-4-diphenyl methyl carboxylate ester) is the important intermediate to prepare cefmetazole, cefotetan, cefbuperazone and cefminox. But there are some defects of the methods whether domestic or foreign, so exploring an environmental and economic synthetic method is particularly important. A synthetic route to prepare 7-MAC of five-step reaction with 7-ACA as starting material was explored in this article based on the analysis of a number of references. 7-TMCA was prepared by the reaction of 7-ACA(cephalosporanic acid) and 1-methyl-5-mercapto-1,2,3,4-tetrazole; then 7-TMCA reacted with diphenyl diazo- methane to get 7-ATCA; Schiff base was gained by the reaction of 7-ATCA and 3,5-ditertbutyl-4-hydroxybenzaldehyde; oxidizing Schiff base with homemade oxidizer to prepare quinone and followed reacting with methanol to get methoxy compound; finally the compound 7-MAC was synthesized by reacting methoxy compound with Girard T reagent. The synthetic route has the advantages of raw materials, mild reaction conditions, fewer reaction steps, short reaction time, less pollution and higher total yield. The overall yield of the route is 61.9% and the liquid purity is 99.21%. The structure of the product was determined by 1H NMR and MS. The synthetic process optimization is as follows: 7-TMCA was synthesized by the reaction of the raw material 7-ACA and 1-methyl-5- mercapto-1,2,3,4-tetrazole with concentrated sulfuric acid as a catalys