Synthesis Of Omeprazole By Catalytic Oxidation With Hydrogen Peroxide

Omeprazole was the first marketed proton pump inhibitor in USA in1989by AstraZeneca, Swedish. Because of the good effect in pepti culcer, high efficiency, low toxin, and high cure rate, Omeprazole has the largest medical sales in the world for several years. It is popular in the world and the market potential is tremendously huge.The traditional synthetic route contains complex procedures, and the technique is too difficult, which restricts the development of the large-scale industrialization. Aiming at this situation, this paper finds the solution in two aspects. First, improve the reaction conditions of key intermediates in procedure, the main purpose contains optimize the synthesis route, reduce the cost and increase the product yield. Second, to achieve the green production process by taking the new reaction reagent to solve the problems which contains chlorination, reduction and oxidation, especially use the green hydrogen peroxide oxidant to realize the purpose of environmental protection.2-mercapto-5-methoxybenzimidazole was synthesized from4-Methoxybenzeneamine, yield62.4%;2-hydroxymethyl-4-methoxy-3,5-dimethylpyridine was synthesized from2,3,5-trimethylpyridine, yield50.6%which are much better than the methods before; the chlorination reagent POCl3was used directly to the next step without separation. The resolution problem of the sulfide was solved well which is precipitating the solids in the water without extraction. By the catalytic oxidation, the final product was successfully synthesized.Omeprazole is not stable under acid conditions, but most of the oxidation methods nowadays using3-Chloroperbenzoic acid as the oxidation reagent, which is the main problem of the development of Omeprazole. In order to solve the difficulties, we claim the procedure above. The entire synthetic route contains13reaction steps. The catalyst was successfully applied in the oxidation of Omeprazole with30%aqueous hydrogen peroxide as oxidant under alkaline conditions in24.4%yield with over99.5%purity.The structure of Omeprazole and intermediates were confirmed by1H NMR, IR, MS, etc.