Amberlyst-15H Cu(ii)-catalyzed diazotization–azidation–cycloaddition: a streamlined route to triazoles from aliphatic amines

Abstract

We present a robust and efficient methodology for the synthesis of 1,2,3-triazoles using aliphatic amines as azide precursors via the azide–alkyne cycloaddition reaction. By substituting the conventional Amberlyst@Cu(II) complex with a Amberlyst-15H catalyst, we reduced the catalyst loading to just 1% (w/w) without compromising efficiency. By employing Amberlyst-15H, a highly sulfonated resin with enhanced catalytic efficiency, we achieved superior stabilization of diazonium ion intermediates and enabled in situ azide generation under milder conditions. This strategic refinement improves the robustness of the synthesis, offering enhanced environmental sustainability as demonstrated by green chemistry metrics (GCMs). Additionally, the methodology was successfully applied to synthesize copper binding chelators such as THETA, THPTA, PPTP, PPTC, and IMTC, which are pivotal in catalytic and coordination chemistry. The versatility of this approach is highlighted through its application to the synthesis of rufinamide, showcasing its potential for broader utilization in chemical synthesis.