Synthesis, Heterocyclization and Anti-Tumour Activity Evaluation of Some Benzimidazole Derivatives

Methylbenzimidazole 1 is converted to imidazole acrylic acid 3 via cyclo condensation with chloral followed by hydrolysis. Compound 3 also obtained from the reaction of o-phenylenediamine with maleic anhydride. Treatment of 1 with SeO₂ yielded the oxidized product 4 (Aldehyde 4) which undergoes Wittig reaction using ester and Ph₃P to furnish the acrylates 5. Compound 5 is also obtained by cyclocondensation of o-phenylenediamine and the corresponding maleate. Cyclization of 3 using Ac₂O provides pyrroloimidazole 6. Imidazole 6 undergoes several transformations using HCl, ammonium hydroxide in neutral medium, o-phenylene diamine/HCl to provide acrylic acid 3, amide 7 and/or bicompound 8 respectively. Anilide 9 is obtained as a result of condensation of 3 with amines. Ester 5 undergoes 1,4-addition to benzimidazole ring to give the corresponding anilino derivative 10. Pyridazine cyclization is acheived by treatment of 5 with NH₂OH in acidic medium. In vitro cytotoxicity is evaluated using SRB (sulphorhodamine-B) assay against two human cell lines, breast and liver carcinoma cell lines. The results show that compound 11 has strong activity against all cell lines tested.