A Practical and Cost-Efficient, One-Pot Conversion of Aldehydes into Nitriles Mediated by ‘Activated DMSO’

Abstract

Participation of ‘activated DMSO’ in the one-pot transformation of aldehydes to nitriles has been described by reacting aldehydes with NH₂OH˙HCl in DMSO in the absence of any added base or catalyst. The method is applicable to access a wide range of aromatic, heterocyclic, and aliphatic nitriles, in which only water is a byproduct. A straightforward and practical procedure is demonstrated on a multigram scale.

activated DMSO - nitriles - aldehydes - dehydration - catalyst

References and Notes

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The products were not contaminated with any side products, such as Pummerer rearrangement products.

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General Procedure for Nitrile Synthesis from Aldehydes
A mixture of aldehyde (1 equiv) and NH₂OH˙HCl (1.1 equiv) in DMSO (3-5 volumes depending on homogeneity of mixture) was stirred at 90 ˚C for 1-2 h. When the reaction was completed as confirmed by TLC (5% EtOAc in hexane), the mixture was cooled and diluted with H₂O. The solid precipitated was collected by filtration, washed with H₂O, and dried under suction to afford the corresponding nitrile in excellent yield. Alternatively, the reaction mixture could be poured onto H₂O and extracted with Et₂O. The organic phase could be evaporated to afford the nitrile with good purity and yield. This method is suitable for the isolation of liquid and aliphatic nitriles.