MCAT Organic Chemistry Review

Aldehyde and Ketones II: Enolates

7.3 Aldol Condensation

The aldol condensation is another vital reaction for the MCAT. This reaction follows the same general mechanism of nucleophilic addition to a carbonyl as previously described. In this case, however, an aldehyde or ketone acts both as an electrophile (in its keto form) and a nucleophile (in its enol or enolate form), and the end result is the formation of a carbon–carbon bond.

As shown in Figure 7.6, when acetaldehyde (ethanal) is treated with a catalytic amount of base, an enolate ion is produced. The enolate is more nucleophilic than the enol because it is negatively charged. This nucleophilic enolate ion can react with the electrophilic carbonyl group of another acetaldehyde molecule. The key to this reaction is that both species are in the same flask. The product is 3-hydroxybutanol, which is an example of an aldol (a molecule that contains both aldehyde and alcohol functional groups). Note that mechanism is still called an aldol reaction even when the reactants are ketones.

Figure 7.6. Aldol Condensation, Step 1: Forming the Aldol An enolate ion is formed, which then attacks the carbonyl carbon, forming an aldol.

KEY CONCEPT

In aldol condensations, it’s the same nucleophilic addition reaction that we have seen before with carbonyl compounds—just with the carbonyl acting as both a nucleophile and an electrophile.

With a strong base and high temperatures, dehydration occurs by an E1 or E2 mechanism: we kick off a water molecule and form a double bond, producing an α,β-unsaturated carbonyl, as shown in Figure 7.7.

Figure 7.7. Aldol Condensation, Step 2: Dehydration of the Aldol The –OH is removed as water (dehydration), forming a double bond.

Aldol condensations are most useful if we only use one type of aldehyde or ketone. If there are multiple aldehydes or ketones, we cannot easily control which will act as the nucleophile and which will act as the electrophile, and a mixture of products will result. This can be prevented if one of the molecules has no α-hydrogens because the α-carbons are quaternary (like benzaldehyde).

This reaction is referred to as a condensation reaction because two molecules are joined with the loss of a small molecule. This type of reaction is also a dehydration reaction because the small molecule that is lost is water.

THE RETRO-ALDOL REACTION

The reverse of this reaction is called a retro-aldol reaction. To push the reaction in a retro-aldol direction, aqueous base is added and heat is applied. The retro-aldol reaction is useful for breaking bonds between the α-and β-carbons of a carbonyl, as shown in Figure 7.8. This reaction is facilitated if the intermediate can be stabilized in the enolate form, just as in the forward reaction.

Figure 7.8. Retro-Aldol Reaction The bond between the α-and β-carbons of a carbonyl is broken.

KEY CONCEPT

In a retro-aldol reaction, a bond is broken between the α-and β-carbons of a carbonyl, forming two aldehydes, two ketones, or one aldehyde and one ketone.

MCAT Concept Check 7.3:

Before you move on, assess your understanding of the material with these questions.

1.    What species acts as the nucleophile in an aldol condensation?

2.    What species acts as the electrophile in an aldol condensation?

3.    What is a retro-aldol reaction? What conditions favor retro-aldol reactions?

4.    The aldol condensation can be classified under many categories of reactions. List some of these reaction types, and provide a short description of each.