Synthesis And Process Optimization Of Levamisole Derivatives

Levamisole,a derivative of imidazo[2,1-b]thiazole,is commonly used as a broad-spectrum deinsect agent.It was found to have immunomodulatory properties in mammals,and had a wide range of pharmacological activities as an adjunct agent in the treatment of colon cancer and melanoma.Therefore,in the thesis,the existing research on levamisole and its derivatives is summarized.Nine levamisole derivatives are designed based on the principles of electron equiarrangement and chemical modification to improve water solubility,the synthesis routes of levamisole derivatives are selected,the synthesis and separation process are optimized,and all target products are characterized..In the synthesis of levamisole,levamisole hydrochloride was determined to be the raw material,which was reacted with strong base to get free levamisole base,and then filtered and extracted to get pure levamisole base.Finally,1.4 equivalent of NaOH was selected as the neutralizing agent,and dichloromethane was used as the extraction agent,with the highest yield reaching 96.84%.In the synthesis and separation of levamisole derivatives,levamisole derivatives were prepared by the reaction of levamisole and bromide.The effects of solvent,molar ratio of reactants,reaction temperature and reaction time on the yield were analyzed by optimizing the process conditions.A relatively reasonable synthesis process was obtained:ethanol was used as the reaction solvent,molar ratio of levamisole to bromide was 1:2,reaction temperature was 60-78℃,reaction time was 12-36 h.The main separation scheme was evaporation,concentration and crystallization,and the secondary separation method was column chromatography.Thus,a synthetic separation method with high yield and purity was obtained,and each target product was characterized by ~1H-NMR.Finally,nine levamisole derivatives which have not been reported were successfully synthesized,which could be further studied..