Phthalimide derivatives were synthesized using the concept of molecular hybridization or combination of two pharmacophores in one drug. In this paper, the concept was utilized to synthesize new antimycobacterial compounds to combat emerging resistant Mycobacterium tuberculosis strains. Four new phthalimides were successfully prepared using a single-step condensation reaction between phthalic anhydride and four different sulfonamides: sulfadimethoxine, sulfathiazole, sulfamethizole, and sulfamethoxypyridazine. IR and 1H NMR spectroscopic and mass spectrometric data verified the identity and structure of the synthesized compounds. The antimycobacterial activity of the synthesized phthalimides and their starting materials was evaluated according to CLSI standard procedures using the agar proportion method. The calculated LogP of both starting materials and phthalimides were also compared.