Preparation method of 2-methylamino-5-chlorobenzophenone

Abstract

The invention discloses a preparation method of 2-methylamino-5-chlorobenzophenone. The method includes the steps of: under the action of a catalyst, subjecting 2-amino-5-chlorobenzophenone and dimethyl carbonate to methylation reaction, thus obtaining 2-methylamino-5-chlorobenzophenone. Compared with existing preparation methods, the method has the advantages of simple preparation, low reaction reagent toxicity, high catalytic activity and selectivity, green and environmental protection and reusable catalyst, easy separation and purification of product, and small equipment corrosion and environmental pollution, can acquire high purity end-product, and is suitable for industrial production, etc.

Description

technical field [0001] The invention belongs to the technical field of medicine and chemical industry, and relates to a preparation method of 2-methylamino-5-chlorobenzophenone. Background technique [0002] 2-Methylamino-5-chlorobenzophenone is often used as a pharmaceutical intermediate, mainly used in the preparation of sedative drugs such as chlordiazepoxide, diazepam (diazepam), and diazepam. [0003] The preparation method of currently known 2-methylamino-5-chlorobenzophenone mainly contains two kinds: [0004] (1) 3-phenyl-5-chloro-2,1-benzisoxazole method [0005] Methylate 3-phenyl-5-chloro-2,1-benzoisoxazole with dimethyl sulfate to generate quaternary ammonium salt; then reduce it with iron powder to obtain 2-methylamino-5-chlorodiphenyl ketone. [0006] [0007] Shen Yiping [Pharmaceutical Industry, 1982, 5, 1-2] first reported the synthesis method. Guan Zuowu et al [Pharmaceutical Industry, 1983, 14 (3), 9-10] carried out methylation and reduction in two ...

AI Technical Summary

Problems solved by technology

The disadvantages are: using dimethyl sulfate as a methylation reagent, which is highly toxic and troublesome to deal with after the reaction; there are many steps, the total yield is lower by 77.6%, and the cost is high

The disadvantages are: the use of dimethyl sulfate as a methylation reagent is highly toxic and troublesome to deal with after the reaction; it is inconvenient to use powdered sodium hydroxide, and the heterogeneous reaction is incomplete; tetrahydrofuran or benzene is used as the reaction solvent, and the post-treatment Need to use ethyl acetate, high solvent cost

The reaction needs to be carried out under the protection of an inert gas. The reaction liquid is relatively viscous, difficult to stir, and will produce a large number of bubbles; the reaction temperature reaches 160°C, and the temperature is too low to slow down or even prevent the reaction.

The disadvantages are: the post-reaction treatment process is complicated, and column separation is required; the reaction lacks selectivity, and the N-monomethylated product 2-methylamino-5-chlorobenzophenone is only 25%, and the N-bis-methylated product Impurities up to 53%

For the use of dimethyl carbonate as a methylation reagent, high silicon aluminum ratio and small grain NaY molecular sieves are used as catalysts to catalyze the direct mono-N-methylation of 2-amino-5-chlorobenzophenone to obtain 2-methylamino-5 - Chlorobenzophenone has not been reported

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