Cyanohydrin reaction

In organic chemistry, a cyanohydrin reaction is an organic reaction in which an aldehyde (−CH=O) or ketone (>C=O) reacts with a cyanide anion (N≡C⁻) or a nitrile (−C≡N) to form a cyanohydrin (>C(OH)C≡N). For example:

Cyanohydrin reaction
Named after	Friedrich Urech
Reaction type	Addition reaction

$${\displaystyle {\ce {R}}{\color {red}{\ce {CH=O}}}+{\ce {R}}{\color {purple}{\ce {C#N}}}\longrightarrow {\ce {R2}}{\color {red}{\ce {C(OH)}}}{\color {purple}{\ce {C#N}}}}$$

This nucleophilic addition is a reversible reaction but with aliphatic carbonyl compounds equilibrium is in favor of the reaction products. The cyanide source can be potassium cyanide (KCN), sodium cyanide (NaCN) or trimethylsilyl cyanide ((CH₃)₃SiCN). With aromatic aldehydes such as benzaldehyde, the benzoin condensation is a competing reaction. The reaction is used in carbohydrate chemistry as a chain extension method for example that of D-xylose.

Examples

Reaction of acetone with sodium cyanide to hydroxyacetonitrile

Reaction of benzoquinone with trimethylsilylcyanide, catalyst KCN is introduced as a 1:1 complex with the Crown ether 18-crown-6

Reaction mechanism

Mechanism of the cyanohydrin reaction

Asymmetric synthesis

The asymmetric cyanohydrin reaction of benzaldehyde with trimethylsilylcyanide is made possible by employment of (R)-Binol^[1] at 1–10% catalyst loading. This ligand firsts reacts with a lithium alkoxy compound to form a lithium binaphtholate Complex.

Asymmetric reaction of benzaldehyde with (R)–Binol–lithium(i-propyloxy) gives (S)-acetonitrile with 98% ee

Asymmetric reaction of benzaldehyde with (R)–Binol–lithium(i-propyloxy) gives (S)-acetonitrile with 98% ee

The chemist Urech in 1872 was the first to synthesize cyanohydrins from ketones with alkali cyanides and acetic acid^[2] and therefore this reaction also goes by the name of Urech cyanohydrin method.