In the present study, a series of novel phthalimide derivatives synthesized because of its potent anti-mycobacterial activity. The title compounds (A1a, A1b, A1 c, A1d, A2a, A2b, A2 c, A2d) have been characterized by TLC, Infrared spectroscopy, H1 NMR and Mass spectroscopy and were evaluated for their anti-mycobacterial activity through MABA (Microplate Alamar blue assay) method. A total of 8 compounds were synthesized and screened for their anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv bacteria. The minimal inhibitory concentrations (MIC) of the compounds were determined. These compounds A1a, A1b, A1c, A1d and A2b showed to be more active than the Nitro phthalimide A2a, A2c, A2d derivatives in inhibition of Mycobacterium tuberculosis growth so these compounds could be considered new lead compounds in the treatment of tuberculosis.