The synthesis of new linear monoazaphenothiazine and its substituted derivatives via nickel catalyzed amidation reaction is reported. This was achieved by the condensation of 2-aminothiophenol and 2,3,5-trichloropyridine in aqueous basic medium to produce a new heterocyclic ring, 3-chloro-1-azaphenothiazine. Upon applying, Buchwald-Hartwig Cross coupling reaction, it leads to the syntheses of an array of new 3-amido derivatives which were obtained in good yields. The structures of the synthesized compounds were established based on their analytical and spectra data

The antimicrobial activity of newly synthesized linear monoazaphenothiazine derivatives; 3-benzamido-1-azaphenothiazine, 3-trifluoromethamido-1-azaphenothiazine, 3-trichloromethanamido-1-azaphenothiazine and 3-(4-nitrobenzamido)-1-azaphenothiazine have been evaluated against bacteria and fungal strains. Results showed that most of the linear monoazaphenothiazine derivatives were significantly active against the tested microorganisms. The correlation between antimicrobial activity and the chemical structure of phenothiazines was discussed.