Recent advances in multicomponent synthesis of 5-substituted 1H-tetrazoles from aldehydes: catalytic methods and green chemistry approaches

Abstract

This review offers a comprehensive overview of recent advancements (2003–2025) in the synthesis of 5-substituted 1H-tetrazoles using aldehyde-based multicomponent reactions (MCRs). It highlights a strategic shift from traditional nitrile–azide cycloadditions to more sustainable and cost-effective procedures. We focus on the design and performance of diverse catalysts, including transition-metal complexes, magnetic nanomaterials, ionic liquids, and sustainable biomass-derived platforms. Furthermore, we explore the distinct mechanistic pathways, such as the oxime- and nitrile-mediated routes, and critically discuss how electronic and steric effects influence reactivity and selectivity of constructing these valuable nitrogen-rich heterocycle. The review also underscores how catalyst innovations have improved atom economy, functional group tolerance, recyclability, and environmental compatibility. By consolidating these developments, this work not only showcases the versatility of aldehyde-based MCR strategies but also provides a roadmap for future research toward scalable and industrially relevant tetrazole synthesis.