Imidazole Hydrochloride Promoted Synthesis of Nitriles from Aldehydes

Background and Objective: As a key pharmacophore, the cyano group widely exists in a variety of biologically active compounds. Besides, nitriles are also valuable intermediates for many common functional groups. In this current work, a new synthesis strategy was developed to obtain nitriles from aldehydes. Methods: Using commercially available aldehydes as raw materials, and hydroxylamine and hydrochloride as nitrogen sources, the corresponding nitrile compounds were successfully synthesized by the one-pot method through the promotion of imidazole hydrochloride. And it was characterized by 1H NMR, 13C NMR, and mass spectrometry. Results: Various reaction conditions were applied in order to find an optimum and convenient procedure for the formation of nitriles. The highest yields (95%) were achieved using sulfolane as a solvent, and imidazole hydrochloride as a promoter. Conclusion: In conclusion, we developed a new synthetic method for nitrile compounds from aldehydes. Twenty seven examples of functionalized nitrile compounds have been synthesized in good to excellent yields. This methodology features that an environmentally benign imidazole hydrochloride replaces transition metal catalysts and oxidants required in conventional strategies to convert aldehydes into nitriles with good functional group tolerability. Further exploration of imidazole hydrochloride is ongoing in our laboratory.