Aldehydes and Ketones with Alcohols: Acetal Formation Mechanism

Unlike hemiacetals, which form under both acid and base-catalyzed conditions, acetals form from hemiacetals only when an acid catalyst is used. Acetal formation involves three major types of reactions: proton transfer, nucleophilic attack, and elimination of the leaving group.

First, the acid catalyst protonates the carbonyl oxygen, which increases the electrophilicity of carbonyl carbon. A molecule of alcohol then attacks the carbon to form an ionic intermediate. This intermediate loses a proton to form the hemiacetal. The hemiacetal thus formed has one -OH and one -OR group attached to the same carbon atom. Due to the weak leaving ability of the -OH group, the incoming nucleophile can not displace the -OH group via a bimolecular substitution mechanism. Hence hemiacetals can not be converted into acetals under basic conditions. The leaving group ability of the -OH group can be enhanced via protonation (using an acid catalyst) to generate a better leaving group—water. Elimination of water generates an oxonium intermediate. This intermediate is attacked by another alcohol molecule which on subsequent deprotonation forms the acetal.

Due to their inertness towards bases and other more common organic reagents, acetals are used as protecting groups capable of safeguarding specific functional groups under diverse reaction conditions.