15.15:
Base-Catalyzed Aldol Addition Reaction
In aqueous sodium hydroxide, two aldehyde molecules undergo an addition reaction to form a β-hydroxy aldehyde. This is a base-catalyzed aldol addition reaction with a multistep mechanism.
The reaction begins with an enolization step, where the hydroxide ion reversibly deprotonates the aldehyde at the α carbon to generate a resonance-stabilized enolate ion.
Next, the nucleophilic addition of the enolate's α carbon to the carbonyl group of the unreacted aldehyde yields an alkoxide ion intermediate.
The subsequent protonation of the alkoxide ion generates a β-hydroxy aldehyde as the aldol addition product. Here, the equilibrium is more favorable in the forward direction.
However, for α-substituted aldehydes, the equilibrium shifts backwards to the precursors due to the steric hindrance at the reaction site.
In ketones, the equilibrium favors the ketone reactant rather than the corresponding aldol addition product.
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