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PTSA-catalyzed selective synthesis and antibacterial evaluation of 1,2-disubstituted benzimidazoles

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Abstract

Herein, we developed a convenient and efficient method via protonation of p-toluenesulfonic acid promoted cyclocondensation of o-phenylenediamine and aldehydes for selectively synthesizing 1,2-disubstituted benzimidazoles. This method displayed broad substrate adaptability and afforded the desired products in moderate to excellent yield in short reaction time. The effect of different substituents on the yield was investigated by extending optimum reaction conditions, which was further confirmed by theoretical calculations. It suggested that the surface electrostatic potential of oxygen atom and nitrogen atom on the substrates played important role in the synthesis of 1,2-disubstituted benzimidazoles. Besides, the crystal structure of compound 2t in the orthorhombic space group P2(1)/c was presented. Also, the anti-mycolicibacterium smegmatis (MC2155) activity was evaluated using rifampicin as a positive control. The products (2a, 2b, 2c, 2i, 2j, 2k, 2m) showed good antibacterial activities which were comparable to rifampicin.

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Acknowledgements

We are grateful to Dr C. Y. Wang for NMR spectra, Dr Z. L. Wei for Ms spectra and Dr L. Ye for single-crystal X-ray structure determination.

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Authors and Affiliations

  1. Department of Chemical Engineering and Applied Chemistry, College of Chemistry, Jilin University, Changchun, 130012, People’s Republic of China

    Jiaxu Fu, Kejun Liu, Shuang Wang, Yiliang Zhang, Qing Su, Qiang Gu & Yumin Zhang

  2. School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China

    Yuandong Yue & Feng Lin

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  1. Jiaxu Fu
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Contributions

JF performed the synthesis of experiments, analyzed the date, the theoretical calculation of ESP and wrote the original draft. YY performed the antimicrobial activity experiments. KL and SW performed the synthesis of some compounds. FL designed and guided antimicrobial activity experiments. YZ optimized geometry configurations of aldehyde. QS performed the analysis of single-crystal X-ray structure. QG designed some experiments. YZ conceived and designed the experiments, explained experimental phenomena and laws, and writing–review & editing.

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Correspondence to Yumin Zhang.

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Fu, J., Yue, Y., Liu, K. et al. PTSA-catalyzed selective synthesis and antibacterial evaluation of 1,2-disubstituted benzimidazoles. Mol Divers 27, 873–887 (2023). https://doi.org/10.1007/s11030-022-10460-2

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