Synthetic Process Research Of Propranolol Hydrochloride

Propranolol Hydrochloride,named 1-Isopropylamino-3-(1-naphthyl oxy)-2- propanol hydrochloride,was the representative ofβ-receptor block medicament,has been applied in clinical already more than 20 years.It was applied for arrhythmia,hypertension,angina and so on.Along with the clinical research continuously thorough,some new use was found.By comparison of the merits and demerits of the processes of the preparation of Propranolol Hydrochloride,on the objective of being friendly to environment,employing less time,being suitable for industrial scale up and so on,chose the better experiment route.In this paper,Propranolol Hydrochloride was synthesized fromα-naphtol and Epichlorohydrin via etherification,amination,acidification research and recrystallization.The optimal synthesis processes of the product and its intermediates are obtained through orthogonal experiments.(1)The optimal synthesis process of 3-(α-Naphthoxyl)-1,2-Epo-xypr opane is as follows:the quality ration 1-naphthol,Epichlorohy-drin is 1: 1;the quality ration triethylamine,1- naphthol is 0.5mL:14.4g;the reacti on temperature is 80～85℃and reaction time is 6h.With this process, the yield is 96.8%and the purity is 91%.(2)The optimal synthesis process of 1-Isopropylamino-3-(1-napht-hy oxyl)-2-propanol is as follows:the quality ration 3-(α-Naphthoxyl)-1,2-E poxypropane,Isopropylamine is 1:3;the reaction temperature is 40～50℃,reaction time is 8h;the quality ration xylene,3-(α-Naphthoxyl)-1,2-E poxypropane is 5:19.9.With this process,the yield is 86.7%and the pu rity is 95%.(3)The optimal synthesis process of 1-Isopropylamino-3-(1-nap-hth yloxy)-2-propanol hydrochloride is as follows:the quality ration hydro chloric acid,1-Isopropylamino-3-(1-naphthyloxy)-2-propanol is 1:1;hydro chloric acid concentration is 12mol/L;the reaction time is 0.5h.With thi s process,the yield is 87.1%and the purity is 96%.Recrystallized the product,the yield is 78%and the purity is 99.5%.The finally yield is 79.3%Through optimal conditions,the synthesis process was improved an d developed,and the goals of yield improveing and process simplificati on were achieved.The yields of each step were reached or surpassed t he yields of the concerned documents,the qualities of the product was met the require.The stru-ctures were confirmend by melting point/IR/¹ HNMR/¹³CNMR.This synthesis process of 1-Isopropylamino-3-(1-naphth yloxy)-2-propanol hydrochloride has had the value of being industrialize d.