科研之友
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摘要
Tuberculosis is a serious bacterial infection in developing countries, especially in areas with drug resistance. The development of the anti-tuberculosis drug ethionamide (ETA) is therefore particularly important. We have designed a new route for ETA synthesis and considered the drug's amenability to large-scale manufacture. We evaluated different routes for the synthesis of ETA and selected the most suitable process for the industrial production of this material, which involved the Minisci reaction of 4-cyanopyridine with propionic acid using a AgNO3/(NH4)(2)S2O8 catalyst system under acidic conditions. The effects of different parameters on the reaction were studied, and the production of the intermediate of 2-ethyl-4-cyanopyridine was twice recrystallized from methanol to obtain pure ETA. In the Minisci reaction, the system was stirred for an additional 20min at 80 degrees C after the addition of ammonium persulphate solution. The subsequent formation of thioamide was conducted at 40 degrees C to 60 degrees C for 1.5h with a 1:5:2 molar ratio of 4-cyanopyridine, propionic acid, and ammonium sulphide. The purity of the crude ETA reached 98.77 % after two recrystallization steps. This process could be scaled up on a much larger scale (1kg), leading to the yield of alkylation reaction and overall yield of the production process as 44.06% and 31.26%, respectively.
- 出版日期2018-3
- 单位北京化工大学
