Acetal formation [ROH/H+]

Acetal formation [ROH/H+] Definition:

Aldehydes and ketones can be converted into acetals and ketals when treated with alcohols and acids.

Acetal formation [ROH/H+] Explained:

Alcohols can be added to carbonyl groups in the same manner as water does. This process can be catalyzed by both acid or base. But the further transformation from hemiacetal to acetal is catalyzed by acid. The equilibrium of the reaction usually favors the starting carbonyl compound. Therefore, hemiacetals usually cannot be isolated. But there are exceptions of which they are most common hemiacetal which can isolable from hydroxy aldehydes and ketones when cyclization leads to the formation of relatively strain-free five- and six-membered rings.This is an intermolecular hemiacetal formation which is common in sugar chemistry.

Mechanism of Acid-catalyzed Acetal Formation

This mechanism consists of two main steps. In the first step, the carbonyl group in the presence of acid is protonated and becomes more electrophilic. The first molecule of alcohol functions as a nucleophile and attacked protonated carbonyl to generate an intermediate oxonium ion. Then, this oxonium intermediate is deprotonated by acid to produce a hemiacetal.

In the second step, acetal is formed by the same treatment as hemiacetal. Begins with the protonation of hydroxide group by acid, thereby converting into an excellent leaving group (water). This leaving of water regenerate the carbon-oxygen double bond, rendering more electrophilic and better for the attack of the nucleophile. The second molecule of the alcohol is added to hemiacetal and generated another oxonium ion. This intermediate ion is deprotonated by acid to produce an acetal.

Each step is reversible which means that the process is governed by an equilibrium. This equilibrium may be shifted in either direction and usually lies to the left for ketones and to the right for aldehydes. Thus, using excess alcohols or removing water favors acetals, and adding excess water favors aldehydes or ketones. They hydrolyzed by aqueous acid and this process is called acetal hydrolysis. Acetals are stable under neutral or basic conditions and they may be isolated as pure substances by neutralizing the acid catalyst used in their formation. As such, they can be used in synthesis for masking or protecting the carbonyl group into a relatively unreactive ether-like moiety. Cyclic acetal formation protects carbonyl groups from attack by a nucleophile.