硝唑尼特的合成研究

Research on the synthesis of nitazoxanide

目的优化硝唑尼特的合成工艺。方法以乙酰水杨酸为原料,氯化亚砜为酰氯化试剂,反应生成乙酰水杨酰氯,再与2-氨基-5-硝基噻唑反应得到目标化合物。粗产品采用乙酸乙酯和水的混合溶液初步纯化,然后使用活性炭脱色处理。结果目标化合物的结构经过MS、1H NMR、13C NMR确证。总收率为53.9%,HPLC纯度为99.83%(>文献值92.8%~99.5%),其中2个杂质的含量分别为0.09%和0.08%。结论优化后的工艺成本低廉,后处理操作简便,终产品的质量符合药物生产要求,适合工业化生产。

ObjectiveTo optimize the synthesis process of nitazoxanide.MethodsAcetylsalicylic acid was used as raw material and thionyl chloride as acyl chloride reagent to produce acetylsalicylic chloride. Then the prepared intermediate was reacted with2-amino-5-nitrothiazole to obtain the target compound. The crude product was initially purified by a mixed solution of ethyl acetate and water,and then decolorized by activated carbon.ResultsThe structure of target compound was confirmed by MS,1 H NMR and13 C NMR. The total yield was 53.9%. The purity by HPLC was 99.83%,higher than the values of 92.8% to 99.5% in the literature,and the contents of two impurities were 0.09% and 0.08%,respectively.ConclusionThe optimized process is of low cost and simple postprocessing operation,and the quality of the final product meets the requirements of pharmaceutical production. Therefore it is suitable for industrial production.