Synthesis of 3-substituted 7-(3,3-dimethyl-1-triazeno)-10-methylphenothiazines as potential antitumor agents

A series of 3-substituted (chloro, bromo, fluoro or methyl) 7-(3,3-dimethyl-1-triazeno)-10-methylphenothiazines were synthesized as potential antitumor agents. Treatment of p-substituted anilines with ammonium thiocyanate in the presence of bromine gave 6-substituted 2-aminobenzthiazoles which, after methylation with methyl iodide were hydrolyzed in 50% potassium hydroxide to give 5-substituted 2-methylaminothiophenols in moderate yield. Condensation of methylaminothiophenols with 3,4-dichloronitrobenzene in ethanol under an atomsphere of nitrogen gave adducts which were cyclized in dimethylformamide under the catalysis of copper and cuprous iodide to give 3-substituted 7-nitro-10-methylphenothiazines. The nitro group was reduced to the amino function with stannous chloride. Diazotization of the amines followed by coupling with dimethylamine gave the corresponding triazenes.