Novel Synthesis of 2-(5-Amino-1, 2, 4-thiadiazol-3-yl)-2-(Z)-methoxyiminoacetic Acid 2-Benzothiazolyl Thioester
2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-(Z)- methoxyiminoacetic acid 2-benzothiazolyl thioester (Ⅲ), an important intermediate of the fourth generation cephalosporins, was efficiently synthesized by thioesterification of 2-(5-amino- 1,2,4-thiadiazol-3-yl)-2-(Z)-methoxyiminoacetic amide (Ⅰ) with 2-mercaptobenzothiazole (Ⅱ) in the presence of triethylamine. Effects of reaction time, temperature, and feeding molar ratio on the yield and quality of the product were investigated, and an improved procedure suitable for industrial production was established. Using piperidine as solvent and triethylamine as catalyst, n(I): n (II)=1.0:1.2, the product was obtained after reflux for 6.0h and identified by FTIR, H NMR and 13C NMR methods. The yield was 76.4％ (Calcd. based on Compound Ⅰ) after recrystallization from THF. The purity of the product is 98.1％ determined by HPLC method. This procedure avoids the use of reducers such as triphenylphosphine and triethylphosphite in the traditional synthesis of the title compound with a satisfactory yield and can serve as an alternative of the traditional procedure due to easy handling, high yield and low cost.
pharmaceutical engineering 2-(5-amino-1, 2, 4-thiadiazol-3-y1)-2-(Z)-methoxyiminoacetic acid 2-benzothiazolyl thioester cephalosporin synthesis
GAO Shihao ZHAO Xinqi
School of Material Science and Technology, Beijing Institute of Technology, Beijing 100081, China
国际会议
第五届科协博士年度科技会议(The 5th Annual Science Conference for Ph.D)
长春
英文
7-10
2007-08-29（万方平台首次上网日期，不代表论文的发表时间）