Synthesis Of Cefotaxime Acid And Cefmenoxime Acid And Exploration Of The Methoxy Cephalosporins Key Intermediate 7-MAC

The development of antibiotics agengts of 7-Amino cephalosporanic acid?7-ACA? as the basic structure was described in this paper.The synthetic routes of the third generation cephalosporins of cefotaxime acid ?CTX? and cefmenoxime acid?CMX-H? and the key intermediate 7?-Methoxy-7?-Amino-3-[?1-methyl-1H-tetrazo-5-yl?thiomethyl]-3-Cephe m-4-carboxylic acid diphenylmethyl ester?7-MAC? were introduced.In addition,the preparation methods of key raw material 7-Amino-3-[[?1-meth -yl-1-H-tetrazo-5-yl?thio]methyl]--3-cephem-4-carboxylic acid?7-AMCA?, intermediates of diphenylmet-hyl 7?-Amino-3-[-?1-methyl-1-H-tetrazo-5 -yl?thiomethyl]-3-cephem-4-carboxylate?7-DAMC? and diphenylmethyl 7-?4-tolysulfenyl-imino?-3-[?1-Methyl-1-H-tetrazo-5-yl?thiomethyl]-3-ceph -em-4-carboxyl-ate?7-DTMC? were introduced and summarized systematically.During the course of exploration about the synthetic technics,the operation parameters of CTX and CMX-H by using 7-ACA or 7-AMCA and AE active ester MAEM as the materials were studied,and the recovery of the by-product benzothiazolyl mercaptan was also explored.Throgh orthogonal optimizing experiments,7-AMCA was synthesized by using 7-ACA and 5-mercapto-1-methyl-1,2,3,4-tetrazole?5-MMT? as the materials.Based on completed experiments,the synthetic conditions of 7-DAMC were optimized,and using 4-tolysulfenyl chloride?TSC? as the amino protection reagent 7-DTMC was synthesized.The 7-MAC synthetic feasibility from 7-DTMC was explored by using non-mercury salt instead of Hg?OAc?₂ as the catalyst.The experimental results showed:?1? By orthogonal optimizing experiments,CTX was obtained at the yield of 86.9%,the purity of 97.96%, and the recovery rate of by-product was 84.7%;?2? Through the optimization of the conditions,the yield of CMX-H was 68.2%,and the purity was 89.61%,that the refinery purity was 92.62%with iso-propanol; ?3? The yield of 7-AMCA was 74.5%and the purity was 95.15%through orthogonal regression experiments;?4? The yield of 7-DAMC was 71.2% and the purity was 96.38%;The yield of 7-DTMC was 77.62%and the purity was 97.10%;?5? It is feasible to prepare 7-MAC by using AgNO₃ or anhydrous AlCl₃ as catalyst instead of mercury acetate.Through the experimental research,CTX and CMX-H were successfully synthesized and the experimental reaction conditions of key material 7-AMCA and some important intermediates 7-DAMC and 7-DTMC were optimized.The synthesis route of 7-MAC from 7-DAMC was got through,and it was identified exactly at last.Through this research projects,it had provided the suitable conditions for the industrial production.