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 Very rare and expensive raw material pyridine derivatives and pentafluorobenzene, tetrafluorobenzene, and the yield is very low, it is difficult to realize industrial production; 4-trichlorobenzene is a raw material, but it will use expensive catalyst, and the yield is not high, it is difficult to realize industrialization; Beilstein Journal of Organic Chemistry, 3(May), No pp.given; 2007, published synthesis repor...

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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 Very rare and expensive raw material pyridine derivatives and pentafluorobenzene, tetrafluorobenzene, and the yield is very low, it is difficult to realize industrial production; 4-trichlorobenzene is a raw material, but it will use expensive catalyst, and the yield is not high, it is difficult to realize industrialization; Beilstein Journal of Organic Chemistry, 3(May), No pp.given; 2007, published synthesis report , its route will use microwave, and the raw material is the derivative of trifluorophenylboronic acid which is very rare and expensive in the market, and the operation is very difficult, and it is also difficult to realize industrial production; Mendeleev Communications, (2), 60-61; 2000 , the published literature also uses very rare and expensive raw material hexafluorobenzene on the market, which 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, Journal of Organic Chemistry, 45(18), 3597-603; 1980, the relevant raw materials used in the public literature report are also very rare and expensive in the market The raw materials are 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, which makes it difficult to separate the product and realize industrialization. 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 is m-difluorobenzene, a highly corrosive hydrogen fluoride gas, and then synthesized by electrochemical methods. The operation is very difficult, and the yield is very low, so it is difficult to realize Industrial production; PCT Int.Appl., 9116287, 31 Oct1991, 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 that produces is not high, and operation difficulty is very great, is difficult to realize suitability for industrialized production; Difficult to realize the cost advantage of industrialization

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