Preparation method of ethyl bromodifluoroacetate

Abstract

The invention belongs to the field of organic synthesis and discloses a preparation method of ethyl bromodifluoroacetate. Difluorobromoacetonitrile is taken as a raw material, and prepared through a one-pot method and subjected to alcoholysis and esterification in ethanol aqueous solution to obtain ethyl bromodifluoroacetate. According to the method provided by the invention, difluorobromoacetonitrile is taken as the raw material and then bromodifluoroacetic acid is subjected to the alcoholysis and esterification after directly hydrolyzed, without generating a toxic bromodifluoroacetyl halide intermediate, and the use of fuming sulfuric acid as an oxidant and bad in operating environments and maximum in pollution, or peroxide or ozone, or oxygen in a high pressure system to result in poor selectivity and very low yield is avoided. Furthermore, the existence of by-products with extremely strong hydrogen halide corrosion of hydrogen fluoride and the like which both have extremely large corrosion to metal and glass-lined materials is avoided in the process, so that the requirements for production reaction equipment are lowered, and the preparation of ethyl bromodifluoroacetate can be carried out in the ordinary glass-lined reaction device.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a preparation method of ethyl difluorobromoacetate. Background technique [0002] Ethyl difluorobromoacetate compound is an intermediate for the synthesis of drugs and high-energy materials. It has been disclosed that the compound is prepared by reacting ethanol with difluorobromoacetyl halide to prepare ethyl difluorobromoacetate, and its chemical reaction formula is as follows: [0003] [0004] Wherein, X can be F, Cl or Br, and difluorobromoacetyl halide can be prepared according to various process methods to prepare difluorobromoacetyl halide (acid chloride, acid bromide and acid fluoride). [0005] In numerous published documents and patents, various process methods are listed in detail, but the fundamental core technology is the preparation technology of difluorobromoacetyl halide, which is basically based on 1,1-difluoro-1-bromo-halogenated Ethane is used...

AI Technical Summary

Problems solved by technology

[0015] (1) 1,1-difluoro-1-bromo-halogenated ethane is used as raw material, basically under the action of oxidant and toxic mercury salt (such as mercuric oxide, mercuric chloride, etc.) to catalyze difluorobromoacetyl Halogen (acyl fluoride, acid chloride and acid bromide, etc.), the oxidant used in this process is either fuming sulfuric acid, which has a harsh operating environment and great pollution; or uses peroxide, oxygen or ozone, or in a high-pressure system, but chooses Poor performance, extremely low yield, and extremely high cost;

[0016] (2) In this process, the intermediate difluorobromoacetyl halide is produced in the form of gas under high temperature conditions and needs to be collected under strong cold conditions to obtain a volatile liquid at normal temperature. The collection process and esterification process Medium, easily hydrolyzed, resulting in extremely low yield

[0018] In addition, in order to improve the oxidation of 1,1-difluoro-1-bromo-halogenated ethane to obtain difluorobromoacetyl halides (acyl fluorides, acid chlorides and acid bromides, etc.), most of them use heavy metal mercury salts (catalysts) which are dangerous to the environment , may produce irreversible damage to the environment

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