Method for synthesizing 5-bromo-2-methoxyphenol

Abstract

The invention discloses a method for synthesizing 5-bromo-2-methoxyphenol, which comprises the steps of protecting phenolic hydroxyl of o-methoxyphenol by using a carbonate reagent, carrying out high-selectivity bromination by using N-bromo succinimide (NBS), and finally hydrolyzing and acidifying to obtain the 5-bromo-2-methoxyphenol. According to the method, o-methoxyphenol is used as a raw material, the carbonic ester reagent is used for acylation protection of phenolic hydroxyl for the first time, the reaction condition is mild, the raw material conversion is thorough, the post-treatment is very convenient, the brominated intermediate can be obtained with high yield only by suction filtration and alcohol washing, and no other by-products are generated. Finally, a target product can beobtained through conventional hydrolysis reaction. The whole reaction process is simple in purification, the solvent in each step can be recycled for multiple times, the comprehensive yield reaches 93%, and the method has a very strong application prospect and is remarkably superior to the prior art.

Description

technical field [0001] The invention belongs to the field of chemistry and relates to a new synthesis process of known compounds, in particular to a method for synthesizing 5-bromo-2-methoxyphenol. Background technique [0002] 5-Bromo-2-methoxyphenol is an important pesticide and pharmaceutical intermediate, and an important raw material for the production of antihypertensive drug Aliskiren. The synthetic routes of 5-bromo-2-methoxyphenol reported in current patents mainly include: [0003] (1) Using guaiacol as a raw material, the phenolic hydroxyl group is protected by sulfonyl or acetyl reagents, and then brominated with N-bromosuccinimide, and finally deprotected. The disadvantages of this route are: sulfo(ethyl)acyl reagents are active in nature, have high requirements on the drying degree of the solvent, and the selectivity of the bromination process is not high, the post-treatment is difficult, and the production conditions are harsh; [0004] (2) Using 5-bromo-2-m...

AI Technical Summary

Problems solved by technology

The disadvantages of this route are: sulfo(ethyl)acyl reagents are active in nature, have high requirements on the drying degree of the solvent, and the selectivity of the bromination process is not high, the post-treatment is difficult, and the production conditions are harsh;

The disadvantage of this route is that 5-bromo-2-methoxybenzaldehyde is more expensive, and the oxidizing agent used is a peroxide, which has potential safety hazards and is difficult to remove after post-treatment

The disadvantages of this route are: the price of raw materials is expensive, and the intermediate nitrosation process has the risk of explosion, unstable properties, and difficult to store

Most of the current acyl groups are acetyl or methanesulfonyl, but this kind of protecting group has a weak positioning effect on bromination, and the selectivity is limited. It is easy to generate by-products at the 3-position, which is difficult to remove

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