Method for preparing 3, 4-difluorobenzaldehyde

Abstract

The invention discloses a method for preparing 3, 4-difluorobenzaldehyde, and relates to the technical field of organic synthesis. The method includes carrying out Grignard exchange reaction on 3, 4-difluoro bromobenzene, tetrahydrofuran and a Grignard reagent to obtain first reaction products; carrying out reaction on the first reaction products and N, N-dimethylformamide to obtain second reaction products; treating the second reaction products to obtain the 3, 4-difluorobenzaldehyde. The 3, 4-difluoro bromobenzene is used as a raw material, and the tetrahydrofuran is used as a solvent. The method has the advantages that the Grignard exchange reaction is carried out on the 3, 4-difluoro bromobenzene and the freshly prepared Grignard reagent which is isopropylmagnesium chloride, and accordingly the problem of large quantities of generated byproducts due to excessively high reaction temperatures when 3, 4-difluoro bromobenzene and a Grignard reagent which is metal magnesium can be solved; the reaction is carried out on the N, N-dimethylformamide and the products already subjected to Grignard exchange, so that the 3, 4-difluorobenzaldehyde can be prepared, and the reaction yield can be increased.

Description

Technical field: [0001] The invention relates to the technical field of organic synthesis, in particular to a preparation method of 3,4-difluorobenzaldehyde. Background technique: [0002] 3,4-Difluorobenzaldehyde is the raw material of the new anti-platelet aggregation drug ticagrelor. Ticagrelor was successfully developed by AstraZeneca in the United States. It is the world's first reversible conjugated oral P2Y12 adenosine Phosphoreceptor antagonists. [0003] Public documents report the method of 2,4-difluorobenzaldehyde, which adopts the process of diazotizing amino groups to add fluorine, which is inconsistent with the idea of ​​this patent. In addition, the preparation of 3,4-difluorobenzaldehyde from raw material 3,4-difluorobromobenzene usually adopts the method of directly making 3,4-difluorobromobenzene and metal magnesium into Grignard reagent, and then reacting with DMF method, but found in the research process, because 3,4-difluorobromobenzene and metal magne...

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Problems solved by technology

[0003] There are reports in the open literature that the method of 2,4-difluorobenzaldehyde uses the process of diazotizing the amino group to add fluorine, which is inconsistent with the idea of ​​this patent

In addition, the preparation of 3,4-difluorobenzaldehyde from raw material 3,4-difluorobromobenzene usually adopts the method of directly making 3,4-difluorobromobenzene and metal magnesium into Grignard reagent, and then reacting with DMF method, but found in the research process, because 3,4-difluorobromobenzene and metal magnesium make Grignard reagent, the temperature must be above 50 ℃, if the temperature is too low, Grignard reagent can not be triggered, but in this Under high temperature, the generated 3,4-difluorophenylmagnesium bromide, due to the strong electron-withdrawing effect of fluorine, will cause the elimination reaction between the 2-position hydrogen of the benzene ring and the Grignard group to generate benzyne, resulting in a high yield of the product. Low, and the impurities are greatly increased

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