Aldol Condensation

The aldol condensation is a type of condensation reaction. It involves the reaction of enol with the aldehyde or ketone. Hence, it forms β-hydroxy aldehyde or ketone. However, this reaction can be catalyzed by the acid or a base. In some cases, aldol products undergo dehydration to produce conjugated enone. The aldol reaction is very important in organic synthesis.

What is Aldol condensation reaction?

“The reaction in which enolate is added to the carbonyl group of an aldehyde and ketone to form ß-hydroxy aldehyde or ketone is known aldol condensation reaction.”

The general reaction of aldol condensation is given below:

BASE CATALYZED aldol condensation

“The two molecules of aldehydes or ketone-containing alpha hydrogen condense in the presence of a base to form ß-hydroxy aldehyde or ketone known as base-catalyzed aldol condensation. “

MECHANISM

The mechanism of the base-catalyzed aldol reaction is given below:

Step 1

In the first step, the base abstract the alpha hydrogen of aldehyde. Hence, it gives a resonance stabilized enolate.

Step 2

In this step, the enolate (nucleophile) attacks the carbonyl carbon of the unionized molecule of aldehyde. Thus it forms an anion of ß-hydroxy aldehyde.

Step 3

This step involves the abstraction of a proton by the alkoxide anion. However, it forms the aldol product.

ACID-CATALYZED ALDOL CONDENSATION

“The condensation of two molecules of aldehyde or ketone in the presence of acid to form aldol product is known acid-catalyzed aldol condensation. “

MECHANISM

The mechanism of acid-catalyzed aldol reaction is as follows:

The retro aldol reaction

Aldol reaction is a reversible reaction. Therefore, the retro aldol reaction converts the aldol products back into the precursors of the aldol reaction. For example, when 4-hydroxy-4-methyl-2-pentanone is heated in the presence of the base. Hence, the final retro aldol product (acetone) is formed.

Mechanism

The retro aldol reaction mechanism starts with removing a proton from the aldol product by the base. However, the C-C bond break with the removal of enolate. Thus, the enolate abstracts the proton, which produces original carbonyl molecules.

 

Dehydration of the aldol addition product

The aldol product t can undergo dehydration. Thus, it leads to the formation of α,β-unsaturated carbonyl compounds. However, these compounds are very stable due to the conjugated double bonds. Therefore, dehydration equilibrium is irreversible.  The mechanism of the dehydration of aldol product is given below:

Intramolecular aldol condensation

Aldol reaction is also involved in the formation of five or six-membered rings. This happens due to intramolecular aldol condensation. For example, the reaction below represents the intramolecular aldol condensation.

This reaction involves the formation of three types of enolate ions. However, the enolate of the ketone adds to the electrophilic carbon of aldehyde. This is because of the greater reactivity of aldehyde towards nucleophilic addition. The mechanism of this reaction is given below:

Crossed aldol condensation

“The aldol reaction which starts with two different carbonyl compounds is crossed aldol condensation.”

However, it leads to a mixture of products.  The reaction of crossed aldol condensation is given below:

Crossed aldol reaction using a weak base

We can use weak bases such as hydroxide for crossed aldol reaction. However, this reaction occurs when one reactant is without alpha hydrogen. The reactant without alpha hydrogen cannot form enolate. Therefore, we avoid the condensation of another reactant.  The concentration of reactant with alpha hydrogen is kept low. However, it takes mostly in its enolate form.  Some examples of this reaction are given below:

In this reaction, dehydration occurs. Which leads to the formation of the double bond. This is because of the presence of extended conjugation.

Crossed aldol reaction using a strong base

The crossed aldol reaction can be done using a strong base such as lithium enolate. This type of reaction is known as directed aldol reaction.

Mechanism

Step 1

In the first step, the strong base lithium diisopropyl amide (LDA) abstracts the alpha hydrogen of the ketone. This results in the formation of lithium enolate.

Step 2

In this step, enolate attacks the electrophilic carbon of aldehyde. Thus, it results in the formation of lithium alkoxide.

Step 3

In the end, water is added for the protonation of lithium alkoxide.

Applications of aldol condensation

There are the following applications of the aldol reaction:

  • It is used in the synthesis of different solvents such as diacetone.
  • It is used in the pharmaceutical industry.
  • It is used in the synthesis of plasticizers.

Concepts Berg

What is crossed aldol condensation?

The crossed aldol condensation is a reaction in which two different carbonyl compounds condense together.  This leads to the formation of a mixture of products.

Why is it called aldol reaction?

The aldol word is related to aldehyde and alcohol. Their resulting product contains aldehyde and alcohol. Therefore, it is known as aldol reaction.

Why is NaOH used in aldol reaction?

NaOH acts as a base. It abstracts the alpha hydrogen of aldehyde or ketone. Hence, it forms an enolate ion.

What is the aldol formula?

The molecular formula of aldol is C4H8O2. 

What is the first step in aldol reaction?

The first step of the aldol reaction involves the formation of an enolate ion. Which is formed by the base.

Reference Books 

  • Organic Chemistry, By Francis A. Carey (University of Virginia)
  • Organic chemistry By T. W. G. Solomons (Department of Chemistry, University of South Florida) & C. B. Fryhle (Chair and Professor of Chemistry at Pacific Lutheran University.

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