Addition of CN - Cyanohydrins

Aldehydes and ketones are converted to cyanohydrins upon treatment with HCN (hydrogen cyanide).

Lab Lore

Arthur Lapworth’s 1903 cyanohydrin mechanism is widely considered the first detailed organic reaction mechanism. He showed that pure HCN reacts slowly, but trace base generates CN⁻ as the active nucleophile—establishing the arrow-pushing logic still used for nucleophilic addition to carbonyls.

HCN is weakly acidic (pKa=9.2), so it does not significantly protonate a carbonyl. Note a protonated ketone has a pKa=-7. The reaction can be catalyzed by the addition of small amounts of NaCN.

Working with HCN is problematic because it is a highly toxic gas. An alternative procedure is to use NaCN in DMSO and then a dilute acid work up.

Mechanism

This mechanism is analogous to hydration under basic conditions. Cyanide ions are an excellent nucleophile attacking the elertophilic carbonyl C atom. An alkoxide intermediate is formed which is subsequently protonated in a mildly acid water work up.

Reactions of Cyanohydrins

Cyanohydrins are useful precursors to α-hydroxy acids and α-hydroxy amines.

Reduction of cyanohydrin to amine

When the nitrile (CN) of a cyanohydrin is reduced a primary amine is produced.

Hydrolysis of cyanohydrin to carboxylic acid

The heating of cyanohydrins with very acid water, results in the hydrolysis of the nitrile group, producing a carboxylic acid.