12.15:
Aldehydes and Ketones with HCN: Cyanohydrin Formation Overview
Mandelonitrile, a defensive chemical produced by millipedes, is an example of a cyanohydrin featuring a cyano and a hydroxyl group on the same carbon atom.
Cyanohydrins are reversibly formed when HCN adds to the carbonyl group.
Aqueous HCN supplies the strongly basic cyanide nucleophile that catalyzes the addition reaction.
However, using HCN alone, cyanohydrin forms at a negligible rate as the weakly acidic HCN produces very few cyanide nucleophiles.
The reaction rate is enhanced by adding a base or KCN to HCN, to generate more CN–, and with that, more cyanohydrin.
With simple aldehydes and most aliphatic ketones, equilibrium favors cyanohydrin formation. However, with aryl and hindered ketones, the carbonyl form predominates.
Here, the forward reaction fails since cyanohydrin formation involves rehybridization from sp2 to sp3 with reduced bond angles and increased steric hindrance that inhibits the nucleophilic attack on the carbonyl carbon.
Cyanohydrins function as synthetic organic intermediates that can be converted to different useful functional groups.
12.15:
Aldehydes and Ketones with HCN: Cyanohydrin Formation Overview
Cyanohydrins are compounds that contain –CN and –OH groups on the same carbon atom. They are formed by the nucleophilic addition of the cyanide ions to the carbonyl group. Cyanide ions are highly basic and nucleophilic and can be generated from HCN under aqueous conditions. However, since HCN is a weak acid, the number of cyanide ions generated is very small. Hence, a small amount of base or KCN/NaCN is added to HCN to increase the concentration of the cyanide ions in the reaction mixture.
Cyanohydrin formation is favored in the case of aldehydes and simple ketones. However, when the bulky groups are present in ketones, the ketone gets sterically hindered, and the equilibrium generally shifts to the left, favoring the reactant.
Cyanohydrins are the key intermediates in the synthesis of various organic compounds. Under acidic hydrolysis conditions, cyanohydrins can be converted into α-hydroxy acids or α,β-unsaturated acids. The conversion to α-hydroxy acids constitutes a key step in the Kiliani–Fischer synthesis of sugars. On the other hand, the reduction of cyanohydrin in the presence of lithium aluminum hydride gives a β-amino alcohol.
Cyanohydrin also occurs in nature in the form of mandelonitrile in millipedes. Millipedes use mandelonitrile as protection against predators and other organisms. Upon release, the mandelonitrile gets converted into benzaldehyde and HCN, preventing other animals from approaching the millipede.