Cyanohydrin
Table of Contents
A cyanohydrin is an organic compound that commonly contains a hydroxyl (-OH) group and a nitrile (-C≡N) group attached to the same carbon atom. [1–4]
The formation of a cyanohydrin introduces a new carbon atom into the original molecule while simultaneously adding a hydroxyl group. As a result, cyanohydrins are valuable synthetic intermediates for the preparation of many other organic compounds.
Cyanohydrins should be treated as hazardous because many are toxic, and some can decompose to produce highly toxic hydrogen cyanide or cyanide ions. Their preparation and handling require appropriate professional laboratory equipment and safety controls.
General Formula
The general formula of a cyanohydrin is: [1–4]
RR’C(OH)C≡N
where R and R‘ may independently be hydrogen, alkyl, or aryl groups.
If one substituent is hydrogen, the cyanohydrin is derived from an aldehyde. If both substituents are carbon-containing groups, it is derived from a ketone.
Some common cyanohydrins are listed below.
| Carbonyl Compound | Carbonyl Formula | Cyanohydrin Formed | Condensed Formula |
|---|---|---|---|
| Formaldehyde | HCHO | Glycolonitrile | HOCH2CN |
| Acetaldehyde | CH3CHO | Lactonitrile | CH3CH(OH)(CN) |
| Acetone | (CH3)2CO | Acetone cyanohydrin | (CH3)2C(OH)(CN) |
| Benzaldehyde | C6H5CHO | Mandelonitrile | C6H5CH(OH)(CN) |
| Cyclohexanone | C6H10O | Cyclohexanone cyanohydrin | C6H10(OH)(CN) |
Structure and Geometry
A cyanohydrin contains a central sp3-hybridized carbon atom bonded to a hydroxyl group, a nitrile group, and two additional substituents, each of which may be hydrogen, alkyl, or aryl. This carbon has a tetrahedral geometry, with bond angles of approximately 109.5°.
In contrast, the carbon and nitrogen atoms of the nitrile group are sp-hybridized. As a result, the atoms around the nitrile carbon are arranged linearly, with a bond angle of 180°.
Physical Properties
| Property | Description |
|---|---|
| Physical state and appearance | Many simple cyanohydrins are colorless liquids or solids when pure, although their appearance depends on molecular structure, purity, and decomposition. [1–4] |
| Polarity | Cyanohydrins are generally polar because they contain both a hydroxyl and a nitrile group. |
| Water solubility | Lower-molecular-weight cyanohydrins tend to be more soluble in water, whereas water solubility generally decreases as the hydrocarbon portion increases. Water may also promote the decomposition of certain cyanohydrins. |
| Organic solvent solubility | Many cyanohydrins are soluble in common polar organic solvents, although their solubility varies with molecular structure. |
| Hydrogen bonding | Cyanohydrins can form intermolecular hydrogen bonds through their hydroxyl groups. |
| Stability | Stability varies with molecular structure and reaction conditions. Because cyanohydrin formation is reversible, some cyanohydrins can regenerate the parent aldehyde or ketone and produce cyanide species, particularly in water, under basic conditions, or at elevated temperatures. The cyanide may be present as HCN or CN– depending on the pH. |
Formation and Mechanism
Cyanohydrins may be prepared by adding hydrogen cyanide to an aldehyde or ketone. In one commonly described method, HCN is generated in situ from sodium cyanide and a dilute acid, such as sulfuric or hydrochloric acid. [1–4]
Cyanohydrin formation proceeds via a two-step nucleophilic addition mechanism.
Step 1: Nucleophilic Attack
The cyanide ion (CN–) acts as a nucleophile and attacks the electrophilic carbonyl carbon through its carbon atom. This forms a new carbon–carbon bond between the cyanide ion and the carbonyl carbon.
At the same time, the electrons of the carbonyl π bond move onto the oxygen atom, producing a tetrahedral alkoxide ion.
Step 2: Protonation
The negatively charged oxygen atom of the alkoxide ion uses a lone pair of electrons to accept a proton from HCN, hydronium (H₃O+), or another suitable proton donor. As the proton is transferred, the electrons of the O–H bond in hydronium return to its oxygen atom, forming water.
Protonation converts the alkoxide group into a hydroxyl group, producing the cyanohydrin.
Stereochemistry
The carbonyl group is planar, so the cyanide ion can attack the carbonyl carbon from either face. If this attack creates a carbon atom bonded to four different groups, that carbon becomes a stereogenic center.
Cyanohydrins formed from aldehydes other than formaldehyde generally contain a stereogenic center because the carbon bearing the hydroxyl and nitrile groups is also bonded to hydrogen and an alkyl or aryl group. Cyanohydrins formed from ketones are stereogenic only when the two carbon-containing groups originally attached to the carbonyl carbon are different.
When an achiral carbonyl compound reacts in an achiral environment, attack from either face is usually equally likely, producing a racemic mixture of two enantiomers. However, a chiral catalyst, enzyme, substrate, or other chiral influence can favor attack at one face, leading to the preferential formation of one stereoisomer. [1–4]
Chemical Properties and Reactions
Cyanohydrins undergo a variety of reactions because they contain both a hydroxyl group and a nitrile group. The reactions available to a cyanohydrin depend on its structure and the reaction conditions. [1–4]
| Reaction | Reagent(s) or Conditions | Product |
|---|---|---|
| Hydrolysis | Dilute aqueous acid, or aqueous base followed by acidification | α-Hydroxy carboxylic acid |
| Reduction | LiAlH4 or catalytic hydrogenation under suitable conditions | β-Amino alcohol, also described as a 1,2-amino alcohol |
| Decomposition | Basic conditions and/or heat; substrate-dependent | Parent aldehyde or ketone + HCN/CN– |
| Dehydration | Acidic dehydrating agent; requires a suitably positioned hydrogen atom | α,β-unsaturated nitrile |
| Esterification | Acid chloride or acid anhydride, usually with a suitable base or catalyst | O-Acylated cyanohydrin, or cyanohydrin ester |
| Oxidation | Suitable oxidizing agent; limited to cyanohydrins that possess a hydrogen on the hydroxyl-bearing carbon | Acyl cyanide, a type of α-oxonitrile |
Applications
Cyanohydrins are useful intermediates in organic synthesis. They can be converted into α-hydroxy acids, amino alcohols, acyl derivatives, and many other functionalized organic compounds. [1–4]
They also have important industrial applications. For example, acetone cyanohydrin is used in an important industrial process for manufacturing methyl methacrylate, the monomer used to produce polymethyl methacrylate and other acrylic materials.
In pharmaceutical and fine-chemical synthesis, cyanohydrins are often used as intermediates in multistep synthetic routes. Their hydroxyl groups may also be temporarily protected so that other parts of the molecule can react selectively.
