Microwave-Enhanced, Additive-Free C-H Amination of Benzoxazoles Catalysed by supported Copper

• DOI: 10.3762/bxiv.2025.14.v1
• Publication Date: 2025-03-04T15:43:36Z
• Authors: Andrei Paraschiv; Valentina Maruzzo; Filippo Pettazzi; Stefano Magliocco; Paolo Inaudi; Daria Brambilla; Gloria Berlier; Giancarlo Cravotto; Katia Martina

The C2 amination of benzoxazole offers wide-ranging potential for substrate expansion and the functionalisation of bioactive compounds. This study presents a green and efficient C-H amination, catalysed by CuCl and CuCl₂, in acetonitrile without acidic, basic or oxidant additives that is accelerated by Microwave (MW) irradiation and is completed in 1.5–2 h. A solid Cu(I) catalyst supported on aminated silica made the process cost-effective and heterogeneous, thus simplifying work-up and minimising free copper in solution. The catalyst was found to be regenerable and reusable for up to eight cycles. The optimised method facilitated the synthesis of various benzoxazole derivatives, demonstrating its versatility and practical applicability.