Preparation method of 1,2,4-trifluoro-benzene

Abstract

The invention relates to a preparation method of 1,2,4-trifluoro-benzene, belonging to the technical field of preparation methods of chemical drug intermediates. The preparation method comprises the following steps of: (1) generating salifying reaction on 3,4-difluoroaniline and fluoboric acid, and then generating diazotization reaction with sodium nitrite to obtain fluoboric acid diazonium salt;and (2) under the solvent-free condition, carrying out high-temperature cracking reaction on the fluoboric acid diazonium salt at the temperature of 80-300 DEG C to obtain 1,2,4-trifluoro-benzene. The preparation method has the advantages of cost saving of raw materials, relatively simple process flow, mild reaction condition, low operation difficulty, operability and convenient aftertreatment; and the prepared products have the purity increased to 98 percent or more now from 80 percent or less originally, are stable in quality, and are suitable for large-scale industrial production.

Description

technical field [0001] The invention belongs to the technical field of preparation methods of chemical drug intermediates, and in particular relates to a preparation method of 1,2,4-trifluorobenzene. Background technique [0002] 1,2,4-Trifluorobenzene is an important intermediate used in the synthesis of many new drugs. At present, there is no relevant literature report in China. The foreign literature Angewandte Chemie, International Edition, 48(12), 2185-2187; 2009, disclosed the synthesis report of 1,2,4-trifluorobenzene, and the raw materials used are market Pyridine derivatives and pentafluorobenzene and tetrafluorobenzene are very rare and expensive raw materials in the world, and the yield is very low, so it is difficult to realize industrial production; PCT Int. , 4-trichlorobenzene is a raw material, but it will use expensive catalysts, and the yield is not high, it is difficult to realize industrialization; Beilstein Journal of Organic Chemistry, 3(May), Nopp.giv...

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Problems solved by technology

At present, there is no relevant literature report in China. The foreign literature Angewandte Chemie, International Edition, 48(12), 2185-2187; 2009, disclosed the synthesis report of 1,2,4-trifluorobenzene, and the raw materials used are market Pyridine derivatives and pentafluorobenzene and tetrafluorobenzene are very rare and expensive raw materials in the world, and the yield is very low, so it is difficult to realize industrial production; PCT Int. , 4-trichlorobenzene is a raw material, but it will use expensive catalysts, and the yield is not high, it is difficult to realize industrialization; Beilstein Journal of Organic Chemistry, 3(May), Nopp.given; 2007, published synthesis report , its route will use microwave, the raw material is very rare and expensive derivatives of raw material trifluorophenylboronic acid on the market, operation difficulty is very big, also is difficult to realize industrialized production; Mendeleev Communications, (2), 60-61; 2000 , the published literature also uses very rare and expensive raw material hexafluorobenzene on the market and is difficult to realize industrial production; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry, (11), 1807-1812; 1998, Journal of the American Chemical Society, 78, 2593-6; 1956, Journal1 of Organic Chemistry, 45 (18), 3597-603; 1980, the relevant raw materials used in the public literature report are also very rare and expensive raw materials on the market, Benzene, fluorobenzene, o-difluorobenzene, m-difluorobenzene, p-difluorobenzene, and the reaction conditions are quite harsh, the yield is not high, and the purity is very poor, making it difficult to separate the product and realize industrial production; U.S. , 5498807, 12 Mar 1996, published bibliographical reports use expensive 2,4,5-trifluorochlorobenzene and palladium carbon catalyst as reaction raw material, and reaction condition is quite harsh and difficult for industrialized production; Electrochimica Acta, 39 (1), 41-9, 1994, the raw material used in the report was m-difluorobenzene, a highly corrosive hydrogen fluoride gas, which was then synthesized by electrochemical methods. The operation was very difficult and the yield was very low, making it difficult to realize industrial production; PCT Int. Appl., 9116287, 31 Oct 1991, Organic Preparations and Procedures International, 23(5), 655-8; In 1991, it was publicly reported that the raw material used was very expensive tert-butyl nitrite on the market, and at the same time, the highly toxic and dangerous boron trifluoride ether solution was used, which was cracked at extremely high temperature and consumed a lot of energy. And the product purity produced is not high, and operation difficulty is extremely great, is difficult to realize suitability for industrialized production; Realize the cost advantage of industrialization

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