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Updated: Jan 13, 2026

Synthesis of a Borylated Ibuprofen Derivative Through Suzuki Cross-Coupling and Alkene Boracarboxylation Reactions
Published on: November 30, 2022
Copper-Catalyzed Site-Specific α-Azidation of Ibuprofen and Naproxen Analogs
Wenqun Zhang1, Ruisheng Zhao1, Dan Liu1
1College of Chemistry and Environmental Science, Inner Mongolia Key Laboratory of Green Catalysis, Inner Mongolia Normal University, Hohhot 010022, China.
None:
Ibuprofen and Naproxen analogs serve as nonsteroidal anti-inflammatory drugs and are the main drugs used to reduce pain, fever, and inflammation. Herein, we report a copper-catalyzed method for the first site-specific α-C(sp3)-H azidation reaction of Ibuprofen and Naproxen analogs. Controlled experiments suggested a unique copper-catalyzed chelation-assisted proton-coupled electron transfer mechanism. The gram-scale synthesis and the ease of nitrogen-based functionalization at the α-site of Ibuprofen and Naproxen analogs provide opportunities to manipulate numerous potential medicinal candidates. Compared to parent Ibuprofen, the α-azido Ibuprofen amide and α-phosphoramidate-substituted Ibuprofen amide showed both higher anti-inflammatory and analgesic activity (statistically significant difference, p < 0.01) in in vivo experiments. Simultaneously, this unique copper-catalyzed chelation-assisted proton-coupled electron transfer strategy paves the way for α-C(sp3)-H activation of ubiquitous carboxylic acids, amides, esters and so on.
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