Novel Synthesis of 2-(5-Amino-l,2,4-thiadiazol-3-yl)-2-(Z)-methoxyiminoacetic Acid 2-Benzothiazolyl Thioester

摘要

2-(5-Amino-l ,2,4-thiadiazoI-3-yl)-2-(Z)-methoxyiminoacetic acid 2-benzothiazolyl thioester (III), an important intermediate of the fourth generation cephaiosporins, was efficiently synthesized by thioesterification of 2-(5-amino-l,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, "( I ):"(II)= 1.0:1.2, the product was obtained after reflux for 6.0 h and identified by FTIR, 'H NMR and 13C NMR methods. The yield was 76.4% (Calcd. based on Compound I) after reciystallization from TUT, The purity of the product is 98 1% determined by HPLC method. This procedure avoids the use of reducers such as tr iphenylphosphine and tr iethylphosphite 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.