15.15 : Base-Catalyzed Aldol Addition Reaction

As depicted in Figure 1, base-catalyzed aldol addition involves adding two carbonyl compounds in aqueous sodium hydroxide to form a β-hydroxy carbonyl compound.

Figure 1: The base-catalyzed aldol addition reaction of aldehydes.

The reaction preferentially occurs with simple aldehydes, where the α carbon is monosubstituted. The equilibrium of the reaction involving disubstituted aldehydes and ketones shifts backward to the reactants due to the steric interactions at the α carbon. The trisubstituted aldehydes with no α hydrogen atom are unsuitable for the aldol addition reaction.

The mechanism occurs in three distinct steps: enolization, nucleophilic addition, and protonation. Firstly, as pictured in Figure 2, the base deprotonates the α carbon of the aldehyde to generate an enolate ion.

Figure 2: The enolization step in the mechanism of the base-catalyzed aldol addition reaction

Figure 3 captures the subsequent nucleophilic addition step. Here, the enolate ion functions as a nucleophile and attacks the carbonyl group of the unreacted aldehyde to form an alkoxide ion intermediate.

Figure 3: The nucleophilic addition step in the base-catalyzed aldol addition reaction mechanism

Finally, as illustrated in Figure 4, the alkoxide ion is protonated to form a β-hydroxy aldehyde as the aldol product. The aldehyde and alcohol functional groups present in the product give the name ‘aldol’ to the reaction.

Figure 4: The protonation step in the mechanism of the base-catalyzed aldol addition reaction