Synthesis Of 2-(Methyl Sulphonyl)-10H-Phenothiazine

As a class of heterocyclic compounds containing N and S elements,penothiazine and its derivatives are important fine cemical products and pharmaceutical intermediates with high biological and pharmacological activity, which are widely used in the biomedical industry.2-(methylsulfonyl)-10H-phenothiazine is a phenothiazine derivative,as an important representative of phenothiazine compounds,it is widely used in synthesis of digestive drugs, psychiatric drugs and so on.Exploring the synthesis of 2-(methylsulfonyl)-10H-phenothiazine, this topic takes 2-bromophenyl thiophenol and chlorobenzenesulfonyl chloride as raw materials. The total product yield is 80.8%. Including the synthesis of the two new intermediate product compounds 1-[(2-bromophenyl) thiol]-4-(methylsulfonyl)-2-nitro-benzene (marked as M1) and of N-[2-(2-bromophenyl) mercapto]-5-[(methylsulfonyl)-phenyl] formamide (marked as M3).Chlorobenzenesulfonyl chloride as raw material which is reduced by sodium sulfite to get 4-benzene sulfonic acid sodium,which is condensed with sodium chloroacetate synthesis of 4-chlorobenzene sulfonyl acetic acid,then 4- chlorobenzene sulfonyl acetic acid is decarboxylat-ed synthesis of chlorophenyl methyl sulfone. The purity is 99.6%, yield is 95.0%, meltin g point is 96.5～98.4℃.Chlorophenyl methyl is purified by carbon tetrachloride and the purity achieves 100%. While the influence of reaction time on the reaction is inspected.Chlorophenyl methyl sulfone as raw material which synthesis of 2-nitro-4-chlorophenyl sulfone with concentrated nitric acid nitration under concentrated sulfuric acid. The purity is 99.9%, yield is 99.7%, meltin g point is 124.2～125.1 ℃.While the influence of reaction time on the reaction is inspected.2-Nitro-4-chlorophenyl sulfone and the sodium salt of 2-bromopHenyl thiophenol as raw materials C-S coupling synthesis of compound M1. The purity is 99.9%, yield is 99.0%, melting point is 162.4～163.0℃. While the influence of different thiophenol sodium salt as raw material and reaction time on the reaction are inspected. The fourth step is that compound M1 as raw material, nitro of which is reduced by hydrazine hydrate synthesis of 2-[(2-bromophenyl) thio]-5-(methylsulfonyl) benzena mine (marked as M2).The purity is 99.9%, yield is 95.4%, meltin g point is 124.2～125.1℃. Comparativing literature reported, 1,2-dichloroethane as solvent, the yield isbhigh. While the influence of activated carbon on the reaction is inspected.Compound M2 as raw material which acylation reaction with formic acid synthesis of M3, The purity is 99.9%, yield is 98.9%, meltin g point is 169.0～169.8 ℃.While the influence of different concentrations of formic acid as the raw material and the reaction time on the reaction are inspected.Compound M3 as raw material condensation,then decarbonylation under the alcohol solution of potassiumhydroxide synthesis of 2-(methylsulfonyl)-10H-phenothiazine. The purity is 98.5%, yield is 91.3%, meltin g point 154.6～155.7℃.While the influence of solvents, the amount of potassiumhydroxide and reaction time on reaction are inspected.On the basis of the relevant literature and experimental research, new process established that 2-bromophenyl thiophenol and chlorobenzenesulfonyl chloride as raw materials synthesis of 2-(methylsulfonyl)-10H-phenothiazine.Final products and intermediates are structure characterizated by the means of FT-IR, GC, GC-MS,ESI-MS,IE-MS, 1H NMR,13C NMR,1H-1HCOSY NMR,13C-1H HSQC NMR and 13C-]H HMBC NMR. The structure is confirmed correct.