Recent Advances in the Synthesis of Imidazole Derivatives: An Overview of Emerging Catalytic Methodologies

Abstract

Imidazole and its derivatives are among the most pharmacologically important nitrogen‐containing heterocycles, with broad use in the design of antifungal, antibacterial, anticancer, and anti‐inflammatory drug design. The Classical routes for synthesis, including the Debus–Radziszewski reaction, van Leusen synthesis, and Wallach synthesis, often involve harsh reaction conditions, limited selectivity, numerous by‐product formation, and poor environmental profiles. In this review, we critically examined recent advances in the synthesis of imidazole derivatives using six distinct catalytic and activation strategies: deep eutectic solvents (DES), magnetic nanoparticle catalysts, microwave‐assisted synthesis, natural acid and biocatalysts, photocatalytic methods, and ultrasound‐assisted synthesis. For each strategy, we discuss representative synthetic protocols, the range of substrates, reaction mechanisms, typical product yields, and catalyst recyclability. Overall, this review demonstrated a clear shift from conventional stoichiometric and energy‐intensive protocols toward greener, reusable catalytic techniques with better alignment for imidazole synthesis.