Catalyst-free technique for synthesizing phenothiazine drug intermediate

Abstract

The invention provides a catalyst-free excellent-regioselectivity weak-alkali-prommoted technique for synthesizing a phenothiazine intermediate. The method comprises the following step: in an inert atmosphere, 2-acetaminophenyl S-thioacetate and o-dihalogenated aromatic hydrocarbons directly react in the presence of a weak alkali to obtain the phenothiazine drug intermediate. The technique is green and environment-friendly, has higher reaction yield of the intermediate for most phenothiazines, and has industrialized application prospects.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and more specifically, it does not need a catalyst, and under the presence of heating and a weak base, S-acetamidophenyl thioacetate and o-dihalogenated aromatics are directly reacted to obtain a phenothiazine drug intermediate body. Background technique [0002] Phenothiazine drugs can be used as drugs for treating mental disorders, for schizophrenia or other psychotic disorders, common ones are: chlorpromazine, perphenazine, fluphenazine, thioridazine, prochlorperazine wait. Therefore, the development of the synthesis of phenothiazine drug intermediates has practical value. [0003] There are relatively few methods for synthesizing phenothiazine intermediates. Unsubstituted phenothiazines can be synthesized by diphenylamine sulfur vulcanization under the catalysis of iodine at high temperature, but a large amount of malodorous and highly toxic hydrogen sulfide is produced. However, some of its...

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Problems solved by technology

[0008] In 2011, Tao et al. used ligand-free CuI to catalyze 2-bromo-N-(2-iodophenyl)aniline and thioacetamide in a reactor Two consecutive C-S couplings give phenothiazines (Synlett, 2011, (1), 134-138); however, its starting material 2-bromo-N-(2-iodophenyl) Aniline has a complex structure and requires multi-step synthesis to obtain