Name: Base-Catalyzed Aldol Addition Reaction
Uploaded: 2023-04-30T10:24:15
Description: Learn by watching this video about Base-Catalyzed Aldol Addition Reaction at JoVE.com

In aqueous sodium hydroxide, two aldehyde molecules undergo an addition reaction to form a &#946;-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 &#945; carbon to generate a resonance-stabilized enolate ion.
Next, the nucleophilic addition of the enolate&#39;s &#945; carbon to the carbonyl group of the unreacted aldehyde yields an alkoxide ion intermediate.
The subsequent protonation of the alkoxide ion generates a &#946;-hydroxy aldehyde as the aldol addition product. Here, the equilibrium is more favorable in the forward direction.
However, for &#945;-substituted aldehydes, the equilibrium shifts backwards to the precursors due to the steric hindrance at the reaction site.&#160;
In ketones, the equilibrium favors the ketone reactant rather than the corresponding aldol addition product.&#160;

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 &#946;-hydroxy carbonyl compound.
<img alt="Figure1" src="/files/ftp_upload/12385/12385-PT_Figure_1.svg" style="text-align: center; height: 60px;" />
Figure 1: The base-catalyzed aldol addition reaction of aldehydes.
The reaction preferentially occurs with simple aldehydes, where the &#945; 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 &#945; carbon. The trisubstituted aldehydes with no &#945; 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 &#945; carbon of the aldehyde to generate an enolate ion.
<img alt="Figure2" src="/files/ftp_upload/12385/12385-PT_Figure_2.svg" style="text-align: center; height: 75px;" />
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.
<img alt="Figure3" src="/files/ftp_upload/12385/12385-PT_Figure_3.svg" style="text-align: center; height: 75px;" />
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 &#946;-hydroxy aldehyde as the aldol product. The aldehyde and alcohol functional groups present in the product give the name &#8216;aldol&#8217; to the reaction.
<img alt="Figure4" src="/files/ftp_upload/12385/12385-PT_Figure_4.svg" style="text-align: center; height: 75px;" />
Figure 4: The protonation step in the mechanism of the base-catalyzed aldol addition reaction

Learn by watching this video about Base-Catalyzed Aldol Addition Reaction at JoVE.com