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 7α-Methoxy-7β-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 7β-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.