Imidazole Hydrochloride Promoted Synthesis of Nitriles from Aldehydes

Abstract

Background and objective: As a key pharmacophore, 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 materias, hydroxylamine hydrochloride as nitrogen source, the corresponding nitrile compounds were successfully synthesized by 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%) was achieved using sulfolane as solvent, imidazole hydrochloride as promoter. Conclusion: In conclusion, we developed a new synthetic method for nitrile compounds from aldehydes. 27 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 to nitriles with good functional group tolerability. Further exploration of imidazole hydrochloride is ongoing in our laboratory.

Green Synthesis of Nitriles from Biomass-Derived Aldehydes by Evoking Intrinsic Cooperative Effects of Ionic Liquids

“…The oxime was protonated in the forms of I-b and I-c , on N with Cl – and on O with Cl – , respectively (Scheme c, polarization of oxime, electrostatic effect). The enhanced nucleophilicity of the Cl – anion in the reaction system provides it with superior activity to attack the imine-H of I-c , resulting in the expulsion of H 2 O (Scheme d, nucleophilic attack). ,, At the same time, the hydrogen-bonding interactions of imines H and the hydroxyl-H of oximes with the Cl – anion as well as the C2/C4/C5–H of [BMIm] + with the hydroxyl-O of oximes promote the activation of C–H and C–OH bonds of oximes (hydrogen-bonding interactions). , All of these interactions synergistically contribute to the dehydration of oximes to nitriles.…”

“…From the perspective of environmental protection and sustainable development, seeking green and safe sources of nitriles, especially using renewable biomass resources, is of great importance. The direct oxidation or dehydrogenation of amines − and dehydration of amides/oximes ,− can allow one to utilize both the carbon and nitrogen sources from the same reactant. However, these feedstocks are limited or one more step is needed to obtain the products.…”