Green Chemistry Synthetic Strategies for Benzimidazole Derivatives with Emphasis on Broad Pharmacological Activities: An Updated Overview

Benzimidazole is a privileged heterocyclic scaffold that has been extensively explored in medicinal chemistry due to its broad spectrum of pharmacological activities, including anticancer, antimicrobial, antiviral, anti-inflammatory, antioxidant, antiparasitic, and central nervous system–related effects. The aim of this study is to systematically review and critically evaluate recent green chemistry–based synthetic strategies for benzimidazole derivatives and correlate these approaches with their pharmacological relevance and structure–activity relationships. This review comprehensively summarizes environmentally benign experimental methodologies, such as microwave- and ultrasound-assisted synthesis, solvent-free mechanochemical grinding, ionic liquids, deep eutectic solvents, heterogeneous catalysis, photocatalysis, biocatalysis, and one-pot multicomponent reactions. These green approaches significantly reduce reaction time, solvent consumption, energy demand, and chemical waste, while improving yields, selectivity, and scalability compared to conventional synthetic routes. The reported results demonstrate that many green methodologies afford benzimidazole derivatives in high yields (often >۸۵–۹۵%) within minutes rather than hours with improved atom economy and reduced E-factors. Furthermore, pharmacological evaluation across multiple studies has revealed that strategically substituted benzimidazole derivatives synthesized via green routes exhibit potent anticancer, antimicrobial, antiviral, anti-inflammatory, and antioxidant activities, supported by structure–activity relationship trends and molecular docking insights. In conclusion, this review highlights that the integration of green chemistry principles with benzimidazole synthesis not only enhances environmental sustainability, but also supports the development of biologically potent and pharmaceutically relevant molecules. These findings emphasize the importance of adopting eco-friendly synthetic methodologies for future benzimidazole-based drug discovery and sustainable pharmaceutical manufacturing.

کلیدواژه ها:

Greenchemistry ، benzimidazole derivatives ، Pharmacological activities ، Anticancer ، SAR ، Molecular docking