Study On Synthesis And Application Of Cysteamine Hydrochloride

Cysteamine hydrochloride is one of the most important medicine intermediates. In this paper, the methods and conditions of synthesis cysteamine hydrochloride (CSH) are investigated. The process route of synthesis CSH, esterification, cyclization, hydrolyzation and ring opening, is established.Sulfuric acid and ethanolamine are employed as raw materials. The synthesis technology of 2-mercaptothiazoline, which is the intermediate of CSH, is studied on. Through the experimental analysis on material rate, mixture temperature, vacuum distillation temperature range, the optimal synthesis conditions are built up: firstly, stirring the mixture solution containing 50% sulfuric acid and 70% ethanolamine solution at room temperature for 30 minutes, then, the solution was distilled at the vacuum 0.095 MP and temperature from 45℃to 145℃, 2-aminoethysulfate was produced after the proceeding. Secondly, reacted 2-aminoethysulfate with carbon disulfide in 20% sodium hydroxide solution, and heated in water bath at 45℃for 2 hours, and then raised the temperature to 55℃until without circumfluence. The second product, 2-mercaptothiazoline, was produced after recrystallization in water. The yield is above 90%, improved more than 20% than before.These methods, such as acid hydrolyzation at atmospheric pressure, alkali hydrolyzation at atmospheric pressure, acid hydrolyzation at high pressure and normal pressure microwave digestion, are employed for the research of ring opening hydrolyzation of 2-mercaptothiazoline. Great deals of comparative experiments are finished. The results present that the velocity of hydrolyzation at high pressure is much faster than the velocity of hydrolyzation at normal pressure, the objected product can be made by acid hydrolyzation or alkali hydrolyzation., the efficiency of microwave digestion is lower than the efficiency of acid hydrolyzation at high pressure. The optimal experimental conditions of acid hydrolyzation are summarized as follows: Mass concentration of hydrochloric acid is 20%, pressure is 0.3MPa, reaction time is 7h, the mole rate of hydrochloric acid to 2-mercaptothiazoline is 5:1. The product purity is 99.0%, the reclamation rate is 95.6%. The optimal conditions of alkali hydrolyzation are as follows: the mole rate of 2-mercaptothiazoline to sodium hydroxide is 1:7; the mass concentration of sodium hydroxide is 30%; distillation time is 3h. The purity of CSH made by alkaline hydrolytic is 98.1%, the reclamation rate is 72.4%. After esterification cyclic reaction, ring opening hydrolyzation, the product was synthesized. The structure of the product was characterized by 1H NMR and IR and the results showed that the product was CSH. The purity rate was determined by Iodometric method. Material balance of the overall synthesis was calculated. The reclamation rate of HCl hydrolyzation at high pressure is 88.7%, the reclamation rate of alkaline hydrolytic at atmospheric pressure is 66.6%. Both of them are made by ethanolamine as benchmark.