Synthesis Of Cephalosporin Intermediates And Research Of Their Complexes

2-(2-amino-4-thiazolyl)-2-(Z)-methoxyiminoacetic acid ( HL1 ) and its derivative 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyiminoacetic acid 2-benzth iazolyl thioester ( AE ) and 2-mercapto-4-methyl-1,3-thiazol-5-yl-acetic acid ( H2L2 ) are important intermediates of many third generation Cephalosporins, and their demands are increased constantly with the development of new Cephalosporins. So it is deserved to work on their synthesis methods.The synthesis methods of intermediates metioned above are researched. The paper is divided into four parts to discuss.1. The novel synthesis method of HL1. The compound is synthesized by using ethyl acetoacetate as raw material followed by steps of oximation, methylination, bromination, cyclocondensation and hydrolyzation. The method focuses on the oximation result in the presense of C2H5NO2 as reaction reagent, the TLC method to detect the bromination process,and the optimized condition of cyclocondensation through orthogonal design experiment. Its total yield is up to 45.7 %, and the structure is confirmed by IR spectrum and melt point of the product.2. The novel synthesis method of AE . The compound is synthesized by using HL1 and 2-(1,3-benzothiazol-2-yldithio)-1, 3-benz othiazole (DM) as raw material , dichloromethane / acetonitrile (volume ratio 1/1) mixture as reaction solvent, and triethyl phosphate replaces the expensive triphenyphosphine. Through orthogonal design experiment the optimized condition is obtained.the material mol ratio of HL1 /DM/ triethylamine /triethyl phosphate is 1/1.05/1.1/1, the reaction temp.is 10¹5℃, and the drop time of triethyl phosphate is 3h, under such condition the yield is up to 86.7 %. The solvents are recycled by distillation in the presence of desiccant.3. The novel synthesis method of H₂L².The compound is synthesized from ethyl...