Hydroxynitriles

A hydroxynitrile is an organic compound with a hydroxyl group (OH) and a nitrile group (C≡N) on the same carbon atom. It is made when an aldehyde or ketone reacts with cyanide ions, followed by dilute acid, in a nucleophilic addition reaction. For example, ethanal gives 2-hydroxypropanenitrile, CH₃CH(OH)CN. Hydroxynitriles are also called cyanohydrins.

What is a hydroxynitrile?

The general structure is a carbon atom carrying an OH group, a C≡N group, and two more groups, R and R′, which can be hydrogen atoms or carbon chains. They come from the two groups that were attached to the C=O carbon of the aldehyde or ketone.

• From an aldehyde (R and H on the carbonyl carbon), the product has R, H, OH and CN on the same carbon.
• From a ketone (two carbon groups on the carbonyl carbon), the product has R, R′, OH and CN on the same carbon.

Making a hydroxynitrile adds one carbon atom to the chain, because the cyanide group brings its own carbon. That makes the reaction useful in synthesis for building longer molecules.

Naming hydroxynitriles

The nitrile group is the main functional group, so the name ends in nitrile, and its carbon is always carbon 1. Count the chain including that carbon, then give the position of the hydroxy group (and any methyl branches).

Notice the hydroxy group is always on carbon 2, next to the nitrile carbon, because that is where the C=O carbon of the starting molecule ends up. Ethanal has two carbons, but its product is a propanenitrile with three.

How hydroxynitriles are made

AQA's A-level specification describes the nucleophilic addition reactions of carbonyl compounds with KCN, followed by dilute acid, to produce hydroxynitriles. In practice, the aldehyde or ketone is mixed with a solution of potassium or sodium cyanide and a little acid, with the pH kept at about 4 to 5, which gives the fastest reaction. Overall, it is the same as adding HCN across the C=O bond:

CH₃CHO + HCN → CH₃CH(OH)CN

The mechanism

The C=O bond is polar: oxygen is more electronegative, so the carbon is δ+ and the oxygen δ−. The mechanism has two stages:

1. Nucleophilic attack. A curly arrow goes from the lone pair on the carbon of the cyanide ion, :CN⁻, to the δ+ carbonyl carbon. At the same time, a second arrow shows the electrons of the C=O double bond moving onto the oxygen. This gives a negatively charged intermediate with O⁻.
2. Protonation. A lone pair on the O⁻ forms a bond to an H⁺ ion, from the acid or from an HCN molecule, giving the OH group.

The bond forms to the carbon of the cyanide ion, not its nitrogen, which is why the new carbon to carbon bond forms and the chain gets longer. The same two-step pattern, with a hydride ion in place of cyanide, reduces aldehydes and ketones to alcohols, as shown in nucleophilic addition.

Hazards of potassium cyanide

AQA expects you to know the hazards of using KCN. Hydrogen cyanide is an extremely poisonous gas, which is why the reaction isn't done with HCN itself. Potassium cyanide is also highly toxic, and adding acid to cyanide releases hydrogen cyanide. So the reaction is carried out with small amounts, in a fume cupboard, with the acid added carefully.

Hydroxynitriles and optical isomers

The C=O group and the atoms joined to the carbonyl carbon all lie in one plane. The cyanide ion can attack that flat carbon from above or below the plane, and both are equally likely.

If the product's central carbon then has four different groups attached, it is a chiral centre, and the two directions of attack give two enantiomers (non-superimposable mirror images) in equal amounts. A 50 : 50 mixture of enantiomers is a racemic mixture. It doesn't rotate plane-polarised light, because the two enantiomers rotate it equally in opposite directions.

The rule from the specification: aldehydes and unsymmetrical ketones form mixtures of enantiomers when they react with KCN followed by dilute acid. Methanal is the exception among aldehydes, because its carbonyl carbon carries two hydrogen atoms.

Reactions of hydroxynitriles

Heat a hydroxynitrile under reflux with dilute hydrochloric acid and the nitrile group is hydrolysed, which turns C≡N into a carboxylic acid group, COOH. From 2-hydroxypropanenitrile this gives 2-hydroxypropanoic acid, better known as lactic acid:

CH₃CH(OH)CN + 2H₂O + HCl → CH₃CH(OH)COOH + NH₄Cl

So a two-step route takes you from an aldehyde to a hydroxy acid with one more carbon: add cyanide, then hydrolyse.

Common mistakes

• Numbering from the wrong end. The nitrile carbon is carbon 1, so the OH is on carbon 2.
• Forgetting the extra carbon. Ethanal (2 carbons) gives a propanenitrile (3 carbons).
• Drawing the cyanide attacking through nitrogen. The lone pair used is on the carbon.
• Calling it electrophilic addition. Alkenes undergo electrophilic addition; carbonyls undergo nucleophilic addition.
• Saying every hydroxynitrile is optically active. A racemic mixture is optically inactive, and products from propanone or methanal aren't chiral at all.

To practise carbonyl chemistry alongside the rest of the second-year course, try today's A-level Chemistry: Year 2 short timed paper.

Read next

Chemistry · Organic chemistryNucleophilic addition: mechanism, NaBH₄ and KCNNucleophilic addition for A-level Chemistry: why aldehydes and ketones react this way, the curly arrow mechanism, reduction with NaBH₄ and KCN with acid.