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Eco-friendly synthesis and antifungal evaluation of N-substituted benzimidazoles

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Abstract

A convenient synthesis of N-phenacylbenzimidazoles in high yields (90–95%) by the N-alkylation reaction of 1H-benzimidazole with phenacyl bromides is provided. The carbonyl group reduction in the products offered the respective N-(2-aryl-2-hydroxyethyl)benzimidazoles in yields up to 97%. In the optimization of reaction conditions for preparing these N-substituted benzimidazoles (ketones and alcohols), a comparative study between eco-friendly methods (microwave and ultrasound) and conventional heating is described. These antifungal azoles analogs were tested for in vitro antifungal activity against Candida albicans and Cryptococcus neoformans, where the alcohols chlorine substituted (4-Cl and 2,4-Cl2) showed the best activity (MIC50 = 31.2 × 10–6 g/cm3).

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Acknowledgements

We thank the Department of Chemistry and Vicerrectoría de Investigaciones at Universidad de los Andes de Bogotá, Colombia for financial support. We express our gratitude to the Colombian Institute for Science and Research (COLCIENCIAS) for the financial support and for the doctoral scholarship conferred to D. V.-O. (Con. 617). We also acknowledge Edwin Guevara for acquiring the high-resolution mass spectra. SZ and EB thank the Universidad Nacional de Rosario, Argentina. EB acknowledges CONICET for a postdoctoral fellowship.

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Authors and Affiliations

  1. Bioorganic Compounds Research Group, Department of Chemistry, Universidad de los Andes, Bogotá, Colombia

    Diana Vargas-Oviedo & Jaime Portilla

  2. Pharmacognosy Area, Faculty of Biochemical and Pharmaceutical Sciences, Universidad Nacional de Rosario, Rosario, Argentina

    Estefanía Butassi & Susana Zacchino

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  1. Diana Vargas-Oviedo
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  2. Estefanía Butassi
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  3. Susana Zacchino
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Correspondence to Jaime Portilla.

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Vargas-Oviedo, D., Butassi, E., Zacchino, S. et al. Eco-friendly synthesis and antifungal evaluation of N-substituted benzimidazoles. Monatsh Chem 151, 575–588 (2020). https://doi.org/10.1007/s00706-020-02575-9

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  • DOI: https://doi.org/10.1007/s00706-020-02575-9

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