Synthesis, structural and antimicrobial studies of some 1-[2-(1H-benzimidazol-1-yl)acetyl]-2,6-diarylpiperidin-4-ones

Abstract

A series of 1-[2-(1H-benzimidazol-1-yl)acetyl]-2,6-diarylpiperidin-4-ones (21-30) has been synthesized under mild conditions in good yield. Structural assignments and conformational analysis of the compounds were established through one-( 1 H and 13 C) and two-dimensional (NOESY and HSQC) NMR studies. A significant upfield shift of proton and carbon at position 'g' of the benzimidazole moiety and phenyl ortho protons of the piperidone system is considered to originate from the anisotropic influence of the suitably positioned π bond containing amide carbonyl group. Dynamic NMR studies proved the existence of restricted rotation and coplanarity of the amide N-C=O carbonyl group and was further confirmed by X-ray crystallographic study of 20. Besides, the rotomers resulting from restricted rotation undergo fastest interconversion on NMR time scale at ambient temperature while at low temperatures, slow exchange occurs leading to a set of signals corresponding to cis and trans rotomers with perfectly equal intensity. The possible factors for the non-broadening of the benzimidazole signals even at very low temperature is explained through dynamic NMR studies. Mass spectral studies indicate a common mode of cleavage among the symmetrically and unsymmetrically substituted analogues. Measurement of antimicrobial activity showed that compounds 23, 24 and 25 exhibited a better activity profile towards the tested microbial strains.