Regioselective Cyanation of Six‐Membered N‐Heteroaromatic Compounds Under Metal‐, Activator‐, Base‐ and Solvent‐Free Conditions

Abstract A regioselective cyanation of heteroaromatic N ‐oxides with trimethylsilyl cyanide has been developed to obtain 2‐substituted N ‐heteroaromatic nitrile without the requirement of any external activator‐, metal‐, base‐, and solvent. The present protocol is a straightforward, one‐pot heteroaromatic C−H cyanation process, and proceeds smoothly in conventional heating but also under microwave irradiation with shorter reaction times. This approach now allows access to a broad class of quinoline N ‐oxides and other heteroarene N ‐oxides with high to good yields and can also be scaled up to obtain gram quantities. Further application of this process was observed and utilized in late‐stage cyanation of the anti‐malarial drug quinine as well as transformation of the 2‐cyanoazines to a series of biologically important molecules. Based on the experimental observations, a plausible mechanism has also been proposed highlighting the dual role of trimethylsilyl cyanide as a nitrile source and as an activating agent. magnified image