The Synthesis Study Of Benzothiazole Thioester

Benzothiazole thioester, one of the side chains of the fourth generationcephalosporin antibiotic, was studied in this paper. Using hydrogen chloride,malononitrile and methanol as the raw materials, benzothiazole thioester wassynthesized with the methods of addition reaction, vacuum distillation, eliminationreaction, cyclization and recrystallization. This synthetic procedure has theadvantages of inexpensive raw materials, mild reaction conditions, simple operationprocess and higher product purity.Temperature, pressure, water content of the reagent, reactants amount andreaction time were important factors of the first four steps. These four factors werefully discussed.3-amino-5-methoxyisoxazole was synthesized; the existed syntheticmethods and conditions of the following steps were summarized. The results areshown as follows:The best conditions of synthesizing methyl cyanoacetimidate hydrochloridewere that, solvent as Ether, materials ratio of malononitrile: methanol: HCl=1:1:1.28,stirring time of normal temperature as7h. The yield of product was97%.The best conditions of synthesizing3,3,3-trimethoxypropionitrile were that,reaction temperature as35℃, reaction time as32h, the by-product ammoniumchloride removed after10hours’ reaction, vacuum degree of concentrating productas0.9MPa, The yield of product was69%.The best conditions of synthesizing3,3-dimethoxyacrylonitrile were that,methanol removed by7～9minutes stirring under222～225℃. The yield of productwas75%and the purity was98.59%.The best conditions of synthesizing3-Amino-5-methoxyisoxazole were that, thestirring time of45℃as3h and stirring time of60℃as3.5h, the best stirring speed of product crystallization as210r/min. The yield of product was74.66%and the puritywas98.91%.