Synthesis and screening of benzothiazole derivatives have great importance in heterocyclic chemistrybecause of its potent and significant biological activities against Salmonella (S) typhiespecially methoxy substitution at benzothiazole. Methoxy substituted benzothiazole derivatives were synthesized by reaction of 3-chloro-4-methoxy-aniline with potassium thiocyanate under temperature control and presence of bromine in glacial acetic acid and ammonia. Substituted nitrobenzamides then synthesized by condensation of, 2-amino-4-chloro-5-methoxy-benzothiazole with 2(3or4)-nitrobenzoylchloride acid in presence of dry pyridine and acetone. Finally, newly synthe-sized derivatives (K-01 to K-09) were synthesized through replacing of chlorine of nitrobenzamide by reaction with 2-nitroaniline, 3-nitroaniline, and 4-nitroaniline in presence of DMF. Analytical characterization was performed by TLC, melting point, IR and NMR spectral study. Antibacterial activity was performed against S. typhiby cup plate method (diffusion technique) using procaine penicillin as standard. Compound K-03 and K-05 showed potent anti-bacterial activity against S. typhiat both concentrations 50μg/ml and 100μg/ml as compared to standard.