A new chemical mechanism for a one-pot synthesis of imidazo[1,2-a]pyridine scaffold as a pharmaceutical intermediate utilizing a robust UiO-66@Fe2O3 hybrid nanocomposite catalyst

In this study, a new hybrid nanocatalyst, UiO-66@Fe 2 O 3 , was designed and synthesized to develop an efficient, thermally stable, and recyclable system for the Ortoleva–King synthesis of pharmaceutically relevant imidazo[1,2-a]pyridine derivatives. The catalyst was prepared via the wet-impregnation method and comprehensively characterized by the XRD, FT-IR, BET, TEM, TGA, ¹H NMR, 13 C NMR, GC-Mass, VSM, XPS and NH₃-TPD analyses. The results confirmed the successful immobilization of Fe 2 O 3 nanoparticles upon the UiO-66 framework, leading to a noticeably high surface area of 1133.8 m² g⁻¹, enhanced thermal stability up to 350 °C (fresh catalyst), and strong magnetic responsiveness enabling facile catalyst separation upon recyclability. In the model reaction between 2-amino-4-methylpyridine and acetophenone, the catalyst afforded the desired product, 2-phenyl-6-methylimidazo[1,2-a]pyridine, at 98.2 % yield within 24 h, with calculated TON and TOF values of 8.06 and 0.336 h⁻¹, respectively. Recycling tests demonstrated that UiO-66@Fe 2 O 3 retained high catalytic activity over five consecutive cycles, with a moderate decline of the yield (from 98.2 to 85.5 %). Post-reaction analyses including XRD, FT-IR, FESEM, TGA, and ICP-based leaching analysis confirmed the preservation of the crystalline structure, functional integrity, and morphological stability of the recovered catalyst, indicating good structural robustness. Compared with previously reported systems, this catalytic protocol integrates high activity with magnetic recoverability and solvent economy. Although chlorobenzene is not a green solvent, it was selected due to its thermal stability under the applied conditions; greener alternatives are under investigation, thus providing a practical and recyclable route to imidazo[1,2-a]pyridine derivatives.