Novel method for preparing benzimidazole proton pump inhibitors

Abstract

The invention provides a novel method for preparing benzimidazole proton pump inhibitors shown in a general formula II. In the presence of [(R'1R'2R'3R'4N)p][AmBnOr] polyoxometallate catalyst shown in a general formula III, 30 percent peroxide is used as an oxidant to ensure that thioether shown in a general formula I is subjected to selective oxidation. (See chart) in the general formula I and the general formulas II, R1, R2 and R3 are equal to H, C1-C5 alkyl, C1-C5 alkoxyl, C1-C5 haloalkyl, C1-C5 ether alkyl, or any combination thereof, and R4 is equal to the H, the C1-C5 alkyl, the C1-C5 alkoxyl, the C1-C5 haloalkyl, or pyrrol-2-yl; and in the general formula III, R'1, R'2, R'3, and R'4 are equal to the H, the C1-C5 alkyl, or any combination of the H and the C1-C5 alkyl, A is metal Mo and W, B is P and the H, x is an integer between 1 and 10, and n, m, p and r are between 0 and 50 or any combination thereof.

Description

technical field [0001] The invention provides a method for preparing benzimidazole proton pump inhibitors which is environmentally friendly, has mild reaction conditions and is economical and effective in production. The method adopts 30% hydrogen peroxide aqueous solution as an oxygen source, and polyoxometalates as a reaction catalyst to prepare benzimidazole proton pump inhibitors, including omeprazole, lansoprazole, rabeprazole, Toprazole and Ilaprazole etc. Background technique [0002] Pyridylsulfinyl-benzimidazole compounds as gastric Na + / K + Proton pump inhibitors, which can inhibit the acid secretion of parietal cells caused by any stimulation, can effectively protect the gastrointestinal mucosa, and are a class of widely used anti-ulcer drugs. This type of compound includes omeprazole, lansoprazole, pantoprazole, rabeprazole, ilaprazole, etc., which are clinically used to slow down and treat gastritis, gastrointestinal ulcer, gastroesophageal reflux, digestive...

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Problems solved by technology

[0005] Chinese patent CN1919844A has described the method that lansoprazole intermediate thioether is oxidized with 30% peroxide aqueous solution in the aqueous solution of acid or alcohol to generate lansoprazole, but the productive rate that obtains is not high, also needs to carry out simultaneously Further purification to increase the purity of the product

[0007] European patent EP0302720, U.S. patents US5578732, US5502195, US7034038, US5470983, etc. respectively describe the use of vanadium compounds as catalysts and aqueous hydrogen peroxide as oxidants to prepare azole-based proton pump inhibitors, resulting in higher yields and less By-products, but the disadvantage is that the vanadium compound catalyst used in the reaction is highly toxic to the human body, and the loss of the catalyst will also cause certain pollution to the environment

[0011] In the above-mentioned published patents for the preparation of prazole compounds, there are mainly the following problems: one is that the catalyst is expensive, or has great toxic and side effects on the human body, and also pollutes the environment; the other is that the catalyst used in some patents The solvent still contains groups such as cyanide and halogen, which increases the production cost and causes great pollution to the environment; the third is that the post-processing of the methods described in some patents is cumbersome and complicated to operate, which increases the production cost and is not conducive to large-scale industries Production

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