Preparation method of 2-fluoro-4-cyano trifluorotoluene

Abstract

The invention relates to the field of synthesis of medical intermediates, in particular to a preparation method of 2-fluoro-4-cyanobenzotrifluoride. The preparation method comprises the following steps: activating zinc powder, preparing a catalyst tetrakis (triphenylphosphine) nickel, adding a main reactant 2-fluoro-4-chlorobenzotrifluoride, and reacting to obtain the 2-fluoro-4-cyanobenzotrifluoride. The raw materials adopted in the method are large in supply in the market and low in price. In the reaction process, full reaction conversion with the prepared activated zinc powder can be realized, so that full conversion is ensured, and generation of impurities is reduced. The conversion yield and the product purity are improved. In the whole process, nitrogen is continuously introduced to ensure that combustibles in the reaction are cooled to a safe state under the protection of inert gas, and meanwhile, air suck-back can be prevented.

Description

technical field [0001] The invention relates to the field of synthesis of pharmaceutical intermediates, in particular to a preparation method of 2-fluoro-4-cyanobenzotrifluoride. Background technique [0002] 2-Fluoro-4-cyanobenzotrifluoride is a very important pharmaceutical intermediate, which is widely used. However, there are many problems in the preparation of 2-fluoro-4-cyanobenzotrifluoride. The following preparations are currently available: Several methods: The first one: the diazotization reaction is the halogen replacement method. The reaction is through the diazonium salt at a slightly higher temperature or under the action of light, especially the diazonium salt containing nitro is very easy to decompose, and some even It can also decompose at room temperature. In a dry state, some diazonium salts are unstable and highly active, and can decompose or even explode when subjected to heat, friction, impact, etc.; the sodium nitrite used in the diazotization product...

AI Technical Summary

Problems solved by technology

In a dry state, some diazonium salts are unstable and highly active, and can decompose or even explode when subjected to heat, friction, impact, etc.; the sodium nitrite used in the diazotization production process is an inorganic oxidant, which can decompose, Reacts with organic matter to cause fire or explosion; the reaction raw materials are explosive

This reaction is a dangerous process, and the cost of raw materials is high, and the market supply is small

The second method: the trifluoromethyl method on the vacancy. The disadvantage of this reaction is that the process is complicated, and the impurity isomers cannot be purified.

The impurity problem, due to the photochlorination reaction process, there will be isomer 2-cyano-4-fluorotrichlorobenzyl, and it is not easy to separate

The third method: acid-change trifluoromethyl method, the disadvantage of this reaction is that the price of raw materials is more than 2 times higher than that of the product

Therefore it can be seen that the existing method preparation process has many problems such as expensive raw materials, long route, high cost, and difficult application in industry.

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