Cyanohydration

Cyanohydration, or cyanohydrin formation, is the chemical process by which aldehydes or ketones react with hydrogen cyanide to give cyanohydrins, compounds bearing both a hydroxyl and a nitrile on the same carbon. The general reaction is R2C=O + HCN → R2C(OH)CN. Cyanohydration is an important method in organic synthesis because the resulting cyanohydrins can be transformed into a variety of useful products, such as alpha-hydroxy acids and other nitrile derivatives.

Mechanistically, cyanohydration involves nucleophilic addition of the cyanide ion to the electrophilic carbonyl carbon, forming a tetrahedral alkoxide intermediate that is subsequently protonated to yield the cyanohydrin. In practice, cyanide is often delivered as hydrogen cyanide gas or as cyanide salts that release cyanide under the reaction conditions. Safer cyanide sources, such as trimethylsilyl cyanide (TMSCN) with a proton source or catalytic systems, are commonly employed. Reactions are typically carried out in protic or polar aprotic solvents and can be catalyzed by acids or bases, depending on the substrate and desired rate.

Scope and limitations vary with carbonyl type. Aldehydes readily form cyanohydrins, especially formal and aryl aldehydes, whereas ketones are less reactive and may require more forcing conditions or catalysts. The reaction is reversible, and the equilibrium can be shifted by temperature, solvent, or removal of HCN. The resulting cyanohydrins often exist as stable, isolable products, though they can be further manipulated, for example by hydrolysis of the nitrile to give alpha-hydroxy acids (as in the preparation of mandelic acid from mandelonitrile).

Safety considerations are important: HCN and cyanide salts are highly toxic, requiring appropriate controls and safer cyanide sources or in situ generation under strict handling conditions.