Three-Component Synthesis of Imidazopyridine Heterocyclic Compounds in Aqueous Microdroplets

The Groebke-Blackburn-Bienaymé (GBB) reaction is among the most efficient strategies for synthesizing imidazopyridines─a class of compounds with diverse biological and pharmacological activities. In our previous work ( Langmuir 2026, 42, 11176-11181), we demonstrated that superacids generated in aqueous microdroplets could catalyze the GBB reaction efficiently at micromolar concentrations under ambient conditions, eliminating the need for external catalysts, high temperatures, or prolonged reaction times typically required in conventional methods. Building on this finding, the present study overcomes interfacial saturation limitations and achieves quantitative conversion at the molar scale by introducing an external catalyst that operates in synergy with the in situ superacids. Specifically, the addition of 2 mol % sodium dodecyl sulfate as a cocatalyst enabled the room-temperature synthesis of 19 imidazopyridine derivatives via microdroplet-assisted GBB reactions, affording good yields (62-90%) and a scalable production rate of 5.25 g h^-1. Overall, this microdroplet-based approach offers a green, efficient, and practical alternative to classical catalytic strategies for preparing imidazopyridine nitrogen heterocycles, aligning well with the principles of sustainable chemistry.