Preparation method for 4-methoxy-1,3-phthalic acid

Abstract

The invention provides a preparation method for 4-methoxy-1,3-phthalic acid. 4-methoxy-1,3-phthalic acid is key intermediate for preparation of an anti-platelet aggregation drug picotamide (with a trade name of plactidil). According to the preparation method, 4-methoxy-1,3-phthalic acid is prepared from the starting raw material p-methylphenol or o-methylphenol through esterification, Fries rearrangement, methylation, oxidation and acidification. Compared with traditional preparation methods, the preparation method provided by the invention has the advantages of low equipment investment, simple operation, quick reaction, high yield, low synthesis cost, greatly reduced environmental pollution and the like, and is particularly suitable for large-scale industrial production.

Description

technical field [0001] The invention relates to a new method for preparing 4-methoxy-1,3-benzenedicarboxylic acid, which is especially suitable for large-scale production of 4-methoxy-1,3-benzenedicarboxylic acid, and has not been reported in literature so far. Background technique [0002] 4-Methoxy-1,3-benzenedicarboxylic acid is a key intermediate in the preparation of the anti-platelet aggregation drug Picotamide (Picotamide, trade name: Plactidil). At present, the relevant literature reports on the synthesis method of 4-methoxyl-1,3-benzenedicarboxylic acid, involving many different raw materials, such as 2,4-dimethylphenol, anisole and o-methyl anisole, etc. The most used method is anisole or 4-methyl anisole as a raw material, which is subjected to chloromethylation by Blanc (Frank) reaction to obtain 2,4-dichloromethyl anisole or 2-chloromethyl 4-Methylanisole is oxidized to obtain the intermediate 4-methoxy-1,3-benzenedicarboxylic acid (Route 1). When this method ...

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Problems solved by technology

This process encountered difficulties in the synthesis of enlarged doses, especially not suitable for large-scale industrial production

There are three main reasons for this. One is that in the Blanc chloromethylation process, large doses of concentrated sulfuric acid and concentrated hydrochloric acid will be used, which will inevitably bring harm to the environment and cause serious corrosion to the equipment, especially the large volume of hydrochloric acid left after the reaction. The problem of storage of waste sulfuric acid and waste hydrochloric acid is particularly serious; the second is that when the synthetic dose is greatly increased, the time for feeding HCl gas is also greatly increased, and the product quality is not easy to guarantee; the third is that feeding HCl gas requires pipelines , sealing and acid-resistant equipment, will increase investment in equipment and labor insurance

Therefore, this synthesis method, which is relatively easy to complete in the laboratory, is difficult to complete in the synthesis process of large-scale dosage, especially in industrial production.

It can be said that these preparation methods in the existing literature are not suitable for industrial scale production

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