Research On Synthesis Of Antiparastic Drug Nitazoxanide

Nitazoxanide, as first member of thiazolides, is a traditionally broad-spectrum high-efficiency antiparasitic and antibacterial drug. Recently, its antiviral research has become a hot spot, of which anti-HBV clinical Ⅱ trails and anti-HCV clinical Ⅲ trails are in progress, anti-Influenza virus clinical Ⅲ trails are also initiated. With its broad market prospects, research on synthetic routes would have potential both on economic and social benefits.There are two mainly synthetic routes, acyl chloride method and direct condensation method in the references, while both of which weren’t ideal ones. Dicyclohexylcarbodiimide (DCC) and N-Hydroxybenzotriazole (HOBT) were usually used as condensation agents in the direct condensation method, which were of high prices, easily solubility in water and difficult wastewater treatment.Moreover, the reaction yield was moderate; thionyl chloride was usually used as acyl chloride agent in the acyl chloride method, so the reaction was always in high temperature, during which acetyl group was easy to fall off and it was prone to esterification, the reaction yield was also moderate.Referring to these synthesized from aspirin to nitazoxanide, traditional acyl chloride was adopted in our experiment. Different from traditional thionyl chloride method, oxalyl chloride, used as acyl chloride agent, would have following advantages:(1) the reaction basically undergo in R.T., so the requirements for devices are low;(2) less side reactions during reaction process, so the reaction yield is high and product is easy to purification;(3) less air pollution, such as SO2during reaction process;(4) oxalyl chloride has a relatively low b.p., so it is easy to evaporate excessive raw material. The optimization of processing conditions has been finished, posttreatment process and recrystallization process are also studied, the final product was more than99.5%purification in HPLC detection, and the product yield was74.9%.A new preparation route, mixed anhydride method, was put forward in our thesis, the advantages of which were high product yield, stable and easily separated intermediate and relatively low requirement for anhydrous condition during process, therefore it was a prospect and promising method. Reaction conditions, like solvent, temperature and material ratio and so on have been optimized, the final product was84.2%purification in HPLC detection, and the product yield was79.2%.Lastly, other synthetic routes, such as symmetric anhydrides method, transesterification method and so on, have also been tested and the results are not satisfied as anticipated.