Study On The New Synthesis Process Of Benfotiamine

Benfotiamine is a fat-soluble derivative of Vitamin B1, applicable to the prevention of Vitamin Bi deficiency, it absorbed more easily than water-soluble Vitamin B1 in the body and more lasting effect, and has many unique medicinal function. Existing reports of Benfotiamine synthesis process has many disadvantages such as harsh reaction conditions, high production cost, high energy consumption and long production cycle. This paper studies a new route for improvement and innovation based on the existing synthesis methods.First, the key intermediate Vitamin Bi phosphate ester was synthesized, with Vitamin Bi as the starting material. Using phosphoric acid after removing water with phosphorus pentoxide to produce poly phosphoric acid as a phosphated reagent, reaction with Vitamin B1, obtain a mixture of Vitamin Bi esters, add alkali metal salts to remove excess phosphoric acid after hydrolysis, the filtrate is concentrated and frozen by the alcohol, yield more than 65%.Second, Benfotiamine is prepared by the acylation reaction of Vitamin Bi phosphate ester and benzoyl chloride. Vitamin Bi phosphate monoester open loop under alkaline conditions, directly adding benzoyl chloride by controlling the pH value in the reaction process, adjusting the pH value to acid obtain benfotiamine crude, crude dissolved under alkaline conditions, decoloration, adjusting the pH value to acid obtain target product, yield 72%.Third, the "one-step" preparation of benfotiamine. After neutralization by alkali metal salt, the filtrate of Vitamin B1 esters directly open loop under alkaline conditions, and then acylation with benzoyl chloride, a step get benfotiamine, no need to extract intermediates phosphate monoester, the yield is up to above 65%.The synthetic route of this paper, using phosphoric acid after removing water with phosphorus pentoxide to produce poly phosphoric acid as a phosphated reagent in esterification, get rid of the present process of high temperature reaction; add alkali metal salts to remove excess phosphoric acid after hydrolysis, the filtrate is concentrated and frozen by the alcohol, avoid the use of expensive solvent and ion exchange column to separation products; In the choice of acylating agent, directly adding benzoyl chloride in aqueous alkaline solution, and the ratio of raw materials, temperature, reaction time, pH value and other parameters on the reaction steps were discussed, to achieve easy operation, reduce the consumption of energy and raw material costs by optimizing the process conditions of each step.