Cyanohydrin reaction

Cyanohydrin reaction
Named after	Friedrich Urech
Reaction type	Addition 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:

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

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 mechanism

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

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.

References

^ Hatano, Manabu; Ikeno, Takumi; Miyamoto, Takashi; Ishihara, Kazuaki (2005). "Chiral Lithium Binaphtholate Aqua Complex as a Highly Effective Asymmetric Catalyst for Cyanohydrin Synthesis". J. Am. Chem. Soc. 127 (31): 10776–77. doi:10.1021/ja051125c. PMID 16076152.
^ Urech, Friedrich (1872). "Ueber einige Cyanderivate des Acetons". Liebigs Ann. 164 (2): 255. doi:10.1002/jlac.18721640207.

External links

Cyanohydrin reaction of formaldehyde to hydroxyacetonitrile or glycolonitrile with sodium cyanide in Organic Syntheses Coll. Vol. 2, p. 387; Vol. 13, p. 56 Article
Cyanohydrin reaction of formaldehyde with potassium cyanide Organic Syntheses Coll. Vol. 3, p. 436; Vol. 27, p. 41 Article
Cyanohydrin reaction of acetophenone with potassium cyanide Organic Syntheses Coll. Vol. 4, p. 58; Vol. 33, p. 7 Article
Cyanohydrin reaction of D-xylose with potassium cyanide Organic Syntheses Coll. Vol. 4, p. 506; Vol. 36, p. 38 Article
Cyanohydrin reaction of acetone with potassium cyanide Organic Syntheses Coll. Vol. 2, p. 7; Vol. 15, p. 1 Article
Cyanohydrin reaction of benzoquinone with trimethylsilylcyanide Organic Syntheses Coll. Vol. 7, p. 517; Vol. 60, p. 126 Article

[1] Hatano, Manabu; Ikeno, Takumi; Miyamoto, Takashi; Ishihara, Kazuaki (2005). "Chiral Lithium Binaphtholate Aqua Complex as a Highly Effective Asymmetric Catalyst for Cyanohydrin Synthesis". J. Am. Chem. Soc. 127 (31): 10776–77. doi:10.1021/ja051125c. PMID 16076152.

[2] Urech, Friedrich (1872). "Ueber einige Cyanderivate des Acetons". Liebigs Ann. 164 (2): 255. doi:10.1002/jlac.18721640207.

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