康 · 学术 | Reaction of the Day No. 1576

Ligand-Accelerated, Copper-Catalyzed Aerobic Oxidative Dehydrogenation of Primary Amines to Nitriles

Shiyun Li,*, Yan An, Lulu Wang, Yu Chen, Jun Huang, Tiesen Li, Bin Wen, and Xingquan Chen*

College of Chemical Engineering, Fuzhou University, Fuzhou 350108, China; Qingyuan Innovation Laboratory, Quanzhou 362801, China;

—ACS Omega 2025, DOI: 10.1021/acsomega.4c11496

Recommended by Yuquan Liu_PT

KEY WORDS:  Cu Catalysis, Amines to Nitriles (反应类型),  C(sp)-N (成键类型), Primary Amines(原料), Nitriles (产物), DMAP (其他)

ABSTRACT: A highly efficient copper-catalyzed oxidative dehydrogenation of primary amines to access nitriles has been developed. We found that DMAP was an efficient ligand for copper-catalyzed oxidation and molecular oxygen was a green oxidizing agent. This reaction exhibited excellent functional group compatibility and a broad substrate scope. Various benzylic, allylic, and aliphatic amines were selectively and effectively oxidized to the corresponding nitriles in high yields (up to 100%). The ligand DMAP not only accelerated the reaction rate but also enhanced the stability of the catalyst. The practicality of the reaction was illustrated on a gram scale, even at a lower catalyst loading and/or under bubble air conditions.

Previous Work

This Work

Proposed Mechanism

Substrate Scope (Selected examples)

Synthetic Applications

Summary and Comments

Prof. Xingquan Chen et al have developed a convenient and efficient copper-catalyzed aerobic oxidative dehydrogenation of primary amines to synthesize nitriles under mild reaction conditions, utilizing dioxygen or air as a green oxidant and DMAP as an extremely efficient ligand. The method can generate excellent yields of nitriles (up to 100%) compatible with multiple functional groups. The mechanism of the reaction was clearly investigated, and the reaction intermediates were captured by HRMS. DMAP as the ligand not only accelerated the reaction rate but also enhanced the stability of the catalyst. This method supports the preparation of nitriles on a gram scale with a lower catalyst loading and under bubble air conditions. Therefore, the catalysis system has the potential for large-scale industrial production. Further applications of copper-catalyzed aerobic oxidation reactions are still ongoing in their group.