Study On The Synthesis Of Thiazolidinedione And Benfotiamine

In this paper, the synthesis of anti-diabetic drug of Benfotiamine,5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzyl]-2,4-thiazolidinedione and its intermediates2.4-thiazolidin-edione were studied.The paper firstly studied the synthesis of2,4-thiazolidinedione.After reviewing the literature, based on the existing process route improvement, came up with a new route, whitch used Easily available, safe operation of ethyl chloroacetate as a starting material, and cyclization with thiourea,then directly hydrolyze into the target product2,4-thiazolidinedione with6N-hydrochloric acid in83.6%yield.Then compared with existing approaches of5-[4-[2-[N-methyl-N-(2-pyridyl)amino] ethoxy]benzyl]-2,4-thiazolidinedione, as a matter of principle to simple operation, excellent yields, lower cost, friendly to environment, eventually, take4steps synthetic route starting from2-chloropyridine. The fist step of the synthesis was the reaction of2-chloropyridine with2-(methylamino)-ethanol. Then the obtained aminopyridine was reacted with4-fluorobenzaldehyde in the presence of aqueous alkali hydroxide solution and phase tansfer catalyst. The later was reacted with2,4-thiazolidinedione.Followed by hydrogenation with20-30%Pd-C. The reaction parameters were optimized. The overall yield was67%, and the amount of Pd on charcoal catalyst substantially lessen. And try novel means of restoring the double bond with1,4-dihydropyridine introducing the fourth step. The yield was very good, and the operation was simple and safe.Finally, the paper was focused on the synthesis of Benfotiamine. The first step was the reaction of thiamine with polyphosphoric acids, then hydrolyze into thiamine monophosphate. Finally, thiamine monophosphate was reacted with benzoylthiosulfate to produce benfotiamine. Through discussing the each step of ratio of reactants, reaction temperature, acidity and other factors, Shorten the reaction time and improve the yield. The overall yield was72%.