Method for synthesizing 4-chloro-3-trifluoromethylaniline by micro-channel reactor

Abstract

The invention provides a method for synthesizing 4-chloro-3-trifluoromethylaniline by a micro-channel reactor, and belongs to the field of synthesis of anti-tumor type medicines in organic synthesis.The invention solves the problems of low yield, poor purity, high energy consumption, danger caused by easy occurrence of severe explosion, degradation caused by long reaction time at high temperatureand high pressure, low catalyst recycling frequency and the like existing in the traditional synthesis method, and provides a method for synthesizing 4-chloro-3-trifluoromethylaniline by a micro-channel reactor. The method particularly comprises the following steps: 1) enabling O-chlorbenzotrifluoride to be subjected to nitration reaction with the mixture of concentrated sulfuric acid and concentrated nitric acid in a reaction module of the micro-channel reactor, and performing after-treatment to obtain 2-chloro-5-nitrobenzotrifluoride; and 2) adding the 2-chloro-5-nitrobenzotrifluoride to anorganic solvent to be dissolved, then adding an active carbon noble metal catalyst and phosphorous acid, adding the components to a preheating module to be mixed and preheated, enabling the preheatedmixture to be subjected to reaction with H2 in the reaction module, and performing after-treatment to obtain 4-chloro-3-trifluoromethylaniline. The method provided by the invention is suitable for large-scale production of 4-chloro-3-trifluoromethylaniline.

Description

technical field [0001] The invention belongs to the field of antitumor drug synthesis in organic synthesis, and in particular relates to a synthesis method of 4-chloro-3-trifluoromethylaniline. Background technique [0002] 4-Chloro-3-trifluoromethylaniline, formula C 7 h 5 CIF 3 N, the chemical structure is as follows: [0003] [0004] The compound is an intermediate for the treatment of primary liver cancer drugs Sorafenib and Regorafenib, and also a key intermediate for the synthesis of fluorine-containing pesticides, with huge market potential. Regarding the synthesis of this compound, there are mainly two kinds of synthetic methods often reported in the literature at present: [0005] method one: [0006] [0007] Using o-chlorotrifluorotoluene as the starting material, nitrate with the mixed acid of nitric acid and sulfuric acid to obtain the nitro compound intermediate, and then through the reduction ring to obtain the amino product 4-chloro-3-trifluoromet...

AI Technical Summary

Problems solved by technology

[0012] In order to solve the problems in the process of synthesizing 4-chloro-3-trifluoromethylaniline in traditional stirred reactors, such as low yield, poor purity, high energy consumption, danger of violent explosion, degradation caused by long reaction time at high temperature, and catalyst recovery Applying mechanically to the problems such as low number of times, the invention provides a kind of method that microchannel reactor synthesizes 4-chloro-3-trifluoromethylaniline, described method comprises the following steps:

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