Ultralarge-Scale Synthesis of Uniformly Dispersive Ultrafine Copper Nanoparticles/Copper(II)-Benzene-1,3,5-tricarboxylate for Selective C2-Acylation of Indole with α-Oxocarboxylic Acids

Copper nanoparticles (CuNPs) are widely used in nanotechnology due to their cost-effectiveness and unique catalytic properties, yet their large-scale synthesis with high activity, stability, and practicality remains challenging. We present an efficient top-down strategy for ultralarge-scale synthesis of uniformly dispersed ultrafine copper nanoparticles/copper(II)-benzene-1,3,5-tricarboxylate (CuNPs/Cu-BTC or CuNPs/HKUST-1, HKUST = Hong Kong University of Science and Technology) using inexpensive copper powder under ambient conditions. Comprehensive characterization (X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), thermogravimetry analysis (TGA), inductively coupled plasma-mass spectrometry (ICP-MS), and Brunauer–Emmett–Teller (BET) analysis) confirmed the successful synthesis of the catalyst featuring 9 nm CuNPs (18% Cu content) uniformly anchored to the metal–organic frameworks (MOFs). The catalyst exhibited excellent performance in the highly selective C2–H acylation of 3-arylazoindoles with α-keto acids, using α-oxocarboxylic acids as acyl sources and K₂S₂O₈ as an oxidant under noble-metal-free conditions. This method features cost-effective, gram-scale synthesis, a broad substrate scope, and exceptional reusability (10 cycles with minimal activity loss). Leaching tests (Sheldon’s method and ICP-MS) confirmed the good heterogeneity of catalyst and good catalytic performance attributed to the well-dispersed CuNPs exposing abundant active sites.