Synthesis, Characterization, and Antimicrobial Evaluation of Benzimidazole - Based Mannich Derivatives

Abstract

A series of benzimidazole derivatives was synthesized by condensing substituted o-phenylenediamines with benzaldehyde in the presence of sodium metabisulfite (Na₂S₂O₅) under reflux in DMF, followed by Mannich reactions with benzaldehyde and dimethylamine. Additional derivatives were obtained via reactions of substituted o-phenylenediamines with N, N-dimethylglycine, yielding intermediates for further Mannich base formation. The synthesized compounds were characterized using melting point determination, TLC, FT-IR, and ¹H-NMR analyses. Antibacterial screening against Staphylococcus aureus and Escherichia coli revealed that compound b2 (Br-substituted) exhibited the highest activity among the synthesized derivatives. Hydroxyl-substituted derivatives showed moderate activity, while unsubstituted analogues were the least effective, confirming the correct trend H < OH < Br. Ciprofloxacin was used as a reference standard and displayed the strongest inhibition zones. Since benzaldehyde remained unsubstituted, the observed differences in biological activity were attributed primarily to substitution patterns on the o-phenylenediamine moiety. These findings underscore the significant influence of o-phenylenediamine substitution on the antimicrobial potency of benzimidazole-linked Mannich bases, highlighting the potential of halogenation, particularly bromine, as an effective strategy for designing novel antimicrobial agents.