The Process For Preparation Of Folic Acid

Folic acid,also known as vitamin M and vitamin B9,which can prevent fetal neural tube defects,cleft lip and other congenital diseases.In addition to lack of folic acid in the body can lead to growth retardation,systemic disease and megaloblastic anemia and other diseases.In this paper,the synthesis process of 2,4,5-trimethyl-amino-6-hydroxy-pyrimidine sulfate has been investigated,and as a raw material for the synthesis of folic acid were studied.In this paper,the characteristics of the two synthetic methods of 2,4,5-triamino-6-hydroxypyrimidine sulfate were compared.Method 1:ethyl cyanoacetate and guanidine hydrochloride as the raw materials reacted under the catalyst of inorganic base,then the 2,4-diamino-6-hydroxypyrimidine was obtained.The 2,4-diamino-6-hydroxypyrimidine was carried out nitrosation reaction and the 2,4-diamino-5-nitrosamines-6-hydroxypyrimidine was produced.The product 2,4-diamino-5-nitrosamines-6-hydroxypyrimidine was hydrogenated and acidized by sulfuric acid,the 2,4,5-triamino-6-hydroxypyrimidine sulfate was obtained.Method 2:the raw material ethyl cyanoacetate was carried out nitrosation reaction then 2-hydroxyimino cyanoacetate was obtained.The 2-hydroxyimino cyanoacetate and guanidine hydrochloride reacted under the catalyst of inorganic base,and 2,4-diamino-5-nitroso-6-hydroxypyrimidine was produced.The 2,4-diamino-5-nitrosamines-6-hydroxypyrimidine was hydrogenated and acidized by sulfuric acid,the 2,4,5-triamino-6-hydroxypyrimidine sulfate was obtained.By comparing the above two methods,it was found that the method 1 is easy to produce 2,4,5-triamino-6-hydroxypyrimidine sulfate in one pot process and the product can be continuously operated,the amount of sodium nitrite consumed less in this step of nitrosation.The nitrosation reaction of method 2 requires more sodium nitrite,but the subsequent steps can reduce the use of acid and alkali.Comprehensive consideration,the method 1 is more advantageous than the method 2 in the synthesis of 2,4,5-triamino-6-hydroxypyrimidine sulfate.1,1,3-trichloroacetone was produced by acetone chlorination in industry,with the purity about 60%,using it as raw material in preparation of folic acid produced a large number of by-products.Based on 1,1,3-trichloroacetone and water can form crystal hydrate and purified by crystallization.GC test showed that 1,1,3-trichloroacetone hydrate purity was about 94.67%.So,the 1,1,3-trichloroacetone as the raw material for the synthesis of folic acid,the yield and purity have been significantly improved.In this paper,folic acid was synthesized with 1,1,3-trichloroacetone,2,4,5-triamino-6-hydroxy pyrimidine sulfate and p-aminobenzoyl-L-glutamic acid.The pH of reaction solution was adjusted by 10%sodium carbonate solution to 3.5.The yield of crude product was 98.69%,with the purity of 75.63%.The crude folic acid was acid refined by 30%sulfuric acid to remove the major impurities such as pterin,and obtained acid purified folic acid with the purity of 92.65%.Then the folic acid was dissolved in sodium hydroxide solution,with hydrochloric acid to adjust the pH to 3.5,folic acid was precipitated.The yield of folic acid was 64.21%and the purity was 97.56%,the yield of folic acid was greatly improved compared with the original process(54%).