15.16:
Acid-Catalyzed Aldol Addition Reaction
Aldol addition reactions of aldehydes or ketones can also be catalyzed by acids.
Recall that the aldol addition reaction is unfavorable for ketones under basic conditions. However, an acid shifts the equilibrium forward to exclusively form the unsaturated carbonyl product instead of an aldol.
Here, the carbonyl group is first activated by protonation to generate protonated ketones. The chloride ion then deprotonates the α carbon to give the enol tautomer as the nucleophile.
At this stage, the solution is a mixture of ketones, protonated ketones, and enol molecules.
To drive the reaction forward, the nucleophilic enol attacks the electrophilic carbon of the protonated ketone, yielding a positively charged intermediate.
The proton loss generates a neutral β-hydroxy ketone as the aldol addition product, which cannot be detected or isolated.
Under acidic conditions, the β-hydroxy ketone spontaneously undergoes dehydration to yield the condensation product.
15.16:
Acid-Catalyzed Aldol Addition Reaction
The aldol reaction of a ketone under acidic conditions successfully forms an unsaturated carbonyl as the final product instead of an aldol. The acid-catalyzed aldol reaction is depicted in Figure 1.
Figure 1. The acid-catalyzed aldol addition reaction of ketones.
First, as shown in Figure 2, the acid protonates the ketone molecule to form the protonated ketone. The conjugate base of the acid deprotonates the α carbon of the protonated ketone to form the enol.
Figure 2. Formation of the enol.
Next, as shown in Figure 3, the enol functions as a nucleophile and attacks the second protonated ketone molecule to form a positively charged intermediate. Finally, the loss of a proton generates a β-hydroxy ketone as the aldol addition product, which dehydrates spontaneously under acidic conditions to form the condensation product.
Figure 3. Nucleophilic addition of the enol and dehydration of the β-hydroxy ketone.