Recent advances in azide-free 1,2,3-triazole construction from diverse nitrogen sources

Abstract

1,2,3-Triazoles represent an important class of five-membered nitrogen heterocycles, exhibiting promising biological activities and material properties that underpin their broad application potential in drug discovery, functional materials, and agrochemicals. While traditional synthetic methods employing azides are well-established, they face inherent limitations, including explosion hazards associated with organic azides and restricted functional group tolerance. In recent years, novel synthetic strategies utilizing alternative nitrogen sources—such as hydrazones, diazo compounds, and nitrite esters/salts—have been developed. These approaches leverage diverse reaction pathways, including [3 + 2] cycloadditions, intramolecular couplings, rearrangement-cyclizations, photo-/electro-catalytic oxidations, and multicomponent couplings, enabling efficient construction of structurally diverse triazole derivatives. This review systematically summarizes strategies for constructing the 1,2,3-triazole ring based on distinct nitrogen sources, focusing primarily on advances from 2017 to 2025. Through in-depth exploration of reaction mechanisms, efficiency, functional group tolerance, and safety, the advantages and limitations of each methodology are critically analyzed. Perspectives on future research directions are also discussed, prioritizing safer nitrogen sources (e.g., oximes), non-precious-metal catalysis, mechanistic studies aided by computation, one-pot tandem reactions, and targeted synthesis of advanced triazole derivatives (e.g., fluorinated or fused-ring). This work aims to provide mechanistic insights and serve as a valuable reference for the safe, efficient, sustainable, and scalable synthesis of functionalized 1,2,3-triazole derivatives.