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Heterocyclic compounds, owing to their structural diversity and unique chemical properties, play a core role in various scientific disciplines, particularly in the evolution of pharmaceuticals. Among these, Benzimidazole (BZID) has captured notable interest due to its remarkable medicinal properties and versatility in biological applications. The pharmaceutical value of BZID is further enhanced by its ability to introduce diverse substitutions at its core, making it a crucial framework in the design of numerous therapeutic agents. However, the need for efficient and sustainable synthetic strategies to explore the full potential of BZID derivatives endures as a key concern. This review article highlights and addresses this gap by examining recent advancements in synthesizing BZID derivatives using aniline derivatives or o-phenylenediamine with aldehydes, acids, alcohols, and their derivatives, as well as amines and halo compounds. This paper discusses various innovative techniques, including ionic liquid catalysis, nano-catalysis, and microwave-assisted methods are emphasized for improving the efficiency and sustainability of reactions. Furthermore, it provides a detailed analysis of the various biological activities of BZID derivatives, such as antibacterial, antifungal, antiviral, and anticancer properties. This article highlights the growing interest in BZID derivatives in modern medicine, as well as underscores their unexplored directions for drug discovery and development.
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