The Wolff-Kishner Reaction

A ketone or an aldehyde is reacted with hydrazine in Wolff-Kishner reduction. The reaction begins with nucleophilic attack of hydrazine upon the carbonyl carbon. This is one of the more challenging mechanisms. Conceptual framing is helpful to learning. Wolff-Kishner belongs to the group of reactions that are possible between ketones/aldehydes and amines and amine derivatives. In these reactions, if the nucleophile is a primary amine, having two hydrogens to lose, reaction with a ketone or an aldehyde will produce an imine form, in which the carbon originally double bonded to oxygen will be double bonded to nitrogen. If the amine is secondary, the product is an enamine, in which the carbon-nitrogen bond is single, but the carbon is double bonded. In Wolff-Kishner, the tetrahedral intermediate formed by the nucleophilic attack, resolves itself by losing the original carbonyl oxygen as hydroxide, forming eventually a hydrazone, the structure of which is of the imine type (not enamine). Deprotonating with a strong base puts electrons on the move within the hydrazone in a manner similar to an elimination mechanism, except that here we have electrons moving into nitrogen-nitrogen bonds, not carbon-carbon, with resonance stability also. Two deprotonations occur moving two electron pairs between the nitrogens, displacing electrons onto the original carbonyl carbon, eventually turning the alkyl portion of the molecule into an E2 style leaving group, which, after departing, is protonated to form the alkane product.