Copper catalytic synthesis phenothiazine compound

Abstract

The invention provides a method for copper catalytic synthesis phenothiazine compound, which is wide in scope of application, excellent in regioselectivity and free of ligand. Ortho-amino aromatic thiophenol and ortho-binary aryl halide are reacted to obtain phenothiazine derivative in inert atmosphere with existence of the copper salt catalytic agent and alkali. Raw materials of the method are easy to obtain, the cost is low, the process is environment-friendly, the great majority of the phenothiazine derivatives are high in synthetic productivity, and the method has industrial application prospects.

Description

technical field [0001] The invention belongs to the fields of organic chemical industry, organic synthesis and drug synthesis, and more specifically relates to the synthesis of phenothiazine compounds by copper catalyzing o-aminoarylthiophenol and o-dihalogenated aromatic hydrocarbons. Background technique [0002] Phenothiazines are synthetic raw materials for drugs, dyes, organic electroluminescent materials, etc., and are also polymerization inhibitors for the production of vinylon, insecticides for fruit trees, and anthelmintics for animals. The phenothiazines derived from it can be used as drugs for the treatment of mental disorders, for schizophrenia or other psychotic disorders. The common ones are: chlorpromazine, perphenazine, fluphenazine, thioridazine, Prochlorperazine etc. Therefore, the development of synthetic methods for phenothiazine compounds has important practical value. There are many synthetic methods of phenothiazine compounds. Phenothiazine can be s...

AI Technical Summary

Problems solved by technology

The raw materials o-iodoarylamine and o-bromoarylthiophenol used in Ma Dawei’s method may undergo self-coupling under the catalysis of CuI to form by-products; the reaction is carried out in two steps, and the cumulative reaction time generally exceeds 100 hours, and the reaction rate is slow; Moreover, o-iodoarylamine and o-bromoarylthiophenol have a narrow range of raw materials, and these raw materials are expensive

Recently, Tao et al. used Ligand-free CuI to catalyze 2-bromo-N-(2-iodophenyl)aniline and thioacetamide for two consecutive C-S couplings in one reactor to obtain phenothiazine ( Synlett, 2011, (1), 134-138); however, its starting material, 2-bromo-N-(2-iodophenyl)aniline, requires a multi-step synthesis to obtain