Efficient synthesis of 1,2-disubstituted benzimidazoles catalyzed by phosphoric acid as a homogeneous catalyst under mild conditions and investigating their anti-diabetes properties through molecular docking studies and calculations

Azam Moazeni Bistgani; Abdulhamid Dehghani; Leila Moradi

doi:10.1039/d3ra07156a

Efficient synthesis of 1,2-disubstituted benzimidazoles catalyzed by phosphoric acid as a homogeneous catalyst under mild conditions and investigating their anti-diabetes properties through molecular docking studies and calculations

RSC Adv. 2023 Dec 8;13(51):35781-35790. doi: 10.1039/d3ra07156a.

Authors

Azam Moazeni Bistgani¹, Abdulhamid Dehghani¹, Leila Moradi¹

Affiliation

¹ Department of Organic Chemistry, Faculty of Chemistry, University of Kashan Kashan P. O. Box 8731753153 Iran l_moradi@kashanu.ac.ir +98 3155912336.

Abstract

A green practical method for the efficient synthesis of 1-benzyl-2-phenyl-benzimidazole and its derivatives using phosphoric acid as an eco-friendly homogeneous catalyst from the condensation reaction of o-phenylenediamine (OPD) and aromatic aldehydes (bearing electron-withdrawing and electron-releasing groups) in methanol under thermal conditions is described. The advantages of this environmentally benign and safe protocol include short reaction times, very mild reaction conditions, excellent yields, not requiring specialized equipment, and simple workup procedures. This method obtained the desired products in moderate to excellent yields between 61-89% within a short period of time of about 13-30 minutes under mild reaction conditions. Finally, with the help of computational chemistry and drug design methods, the anti-diabetic properties of these compounds were studied and investigated. All the synthesized compounds bind to an agonist in the active site of the 4ll1 protein. These connections lead to the inactivation of this protein and create beneficial effects during the treatment of diabetes. In the synthesized compounds, one of the ligands establishes hydrogen bonds with glutamine 107 residues through nitrogens, and in addition, it establishes Π bonds with tyrosine 72. In this study, it was found that these compounds have the potential to become an oral anti-diabetic drug.