Important Nucleophilic Addition Reactions

A range of common nucleophiles all add to the carbonyl group by the general mechanism of §8.5, but differ in what final product results once the tetrahedral intermediate is formed.

Hydrogen cyanide -- cyanohydrin formation. $\text{HCN}$ itself is a poor nucleophile source (it barely ionises, and molecular $\text{HCN}$ is a weak acid, not an effective attacking species), so the reaction is normally carried out with a trace of base such as $\text{KCN}$ added, which generates a small, steady concentration of the far more nucleophilic cyanide ion, $\text{CN}^-$. The cyanide ion attacks the carbonyl carbon to give a tetrahedral alkoxide intermediate, which is then protonated (by $\text{HCN}$ itself, regenerating a little $\text{CN}^-$ to continue the cycle) to give an $\alpha$-hydroxynitrile (a cyanohydrin), $\text{R}_2\text{C(OH)CN}$.

Sodium bisulphite -- an addition compound used for purification. Saturated aqueous $\text{NaHSO}_3$ adds across the carbonyl group of an aldehyde or a methyl ketone (bulkier ketones are usually too hindered to react) through the nucleophilic sulphur atom of the bisulphite ion, giving a crystalline, water-soluble $\alpha$-hydroxysulphonate salt. Because this addition is reversible, treating the isolated crystalline adduct with dilute acid or base regenerates the original pure carbonyl compound -- a classic method for purifying and isolating aldehydes and methyl ketones from a mixture.

Alcohols -- hemiacetal and acetal formation. One equivalent of an alcohol adds to an aldehyde (catalysed by dry $\text{HCl}$ gas) to give a hemiacetal, $\text{R-CH(OH)(OR}'\text{)}$; because the hemiacetal is itself in equilibrium with excess alcohol, a second equivalent then substitutes for the remaining $\text{-OH}$ (via loss of water and attack by a second alcohol molecule on the resulting oxocarbenium ion) to give a stable acetal, $\text{R-CH(OR}'\text{)}_2$, with two ether-like $\text{-OR}'$ groups on the same carbon. Because every step of acetal formation is an equilibrium, an acetal is readily hydrolysed back to the parent aldehyde and alcohol by dilute aqueous acid -- but, importantly, an acetal is completely stable to base. This makes the acetal a valuable protecting group: a synthetic chemist can convert an aldehyde to its acetal before carrying out a base-sensitive reaction elsewhere in the molecule, then remove the protecting group afterwards with dilute acid to reveal the aldehyde again. Ketones react analogously but more slowly, giving ketals.

Grignard reagents -- alcohol formation. A Grignard reagent, $\text{RMgX}$, adds its carbanion-like alkyl/aryl group to the carbonyl carbon to give, after aqueous acid work-up, an alcohol: addition to formaldehyde gives a primary alcohol, addition to any other aldehyde gives a secondary alcohol, and addition to a ketone gives a tertiary alcohol. …