CHE 416-ORGANIC SYNTHESIS

Methods of forming Carbon- Carbon Bonds

1. Aldol Condensation Reactions

Aldol Condensation Reactions

1
 ● Important terms to note:
➔ Condensation- is a reaction in which two molecules combine to form larger
molecules with elimination of a small molecule.
➔ Aldol Condensation- a sequence of reactions consisting of the aldol addition
reaction followed by dehydration/elimination of water to give the unsaturated
carbonyl product.
➔ 𝞪 Carbon- A carbon adjacent to a carbonyl group.
➔ 𝞪 Hydrogen- A hydrogen on a 𝞪 carbon.
➔ Enolate ion-is the anion formed when an alpha hydrogen in the molecule of an
aldehyde or a ketone is removed as a hydrogen ion.

Aldol Condensation Reactions

2
 Introduction to aldol condensation
reaction
In Organic synthesis, Aldol condensation allows formation of carbon-carbon bond by base
catalysis of aldehydes and ketones. This reaction is important because In its usual form, it
involves the nucleophilic addition of a ketone enolate to an aldehyde to form a β-hydroxy
ketone, or "aldol" (aldehyde + alcohol), a structural unit found in many naturally occurring
molecules and pharmaceuticals.
The general reaction of aldol condensation is as follows:-

Aldol Condensation Reactions

3
 Mechanism of Aldol Reactions
1. Step One - Enolate Formation
In the presence of a base (OH) the acidic α-hydrogen is removed from the
aldehyde/ketone ,through a process known as deprotonation to give an enolate and
a water molecule

Aldol Condensation Reactions

4
 Mechanism of Aldol Reactions
1. Step One - Enolate Formation
Enolate ions are resonance stabilized. e.g

Aldol Condensation Reactions

5
 Mechanism of Aldol Condensation
Reactions
2. Nucleophilic attack by the enolate
The nucleophilic enolate attacks the aldehyde at the electrophilic carbonyl C in a
nucleophilic addition reaction giving an intermediate alkoxide

Aldol Condensation Reactions

6
 Mechanism of Aldol Condensation
Reactions
3. Protonation
An acid –base reaction takes place , where the alkoxide deprotonates a water
molecule creating hydroxide and the β-hydroxylaldehyde ,the aldol product.

Aldol Condensation Reactions

7
 Mechanism of Aldol Condensation
Reactions:
4. Dehydration of Aldol products to synthesize α, β unsaturated
carbonyl (enones)
The products of aldol reactions often undergo a subsequent elimination of water, made up
of an alpha-hydrogen and the beta-hydroxyl group. The product of this elimination
reaction is an α,β-unsaturated aldehyde or ketone. An example is below

Aldol Condensation Reactions

8
 Overview of Aldol condensation
reactions.

Aldol Condensation Reactions

9
 Examples of aldol condensation
reactions.
Example One
The reaction of Acetone in presence of NaOH (a base) to form a 𝜷- hdroxylketone and on
condensation to form an 𝛂,𝜷-unsaturated ketone( called an enone

Aldol Condensation Reactions

10
 Examples of aldol condensation
reactions.
Example Two- Cross Aldol Condensation
A crossed aldol condensation uses two different aldehyde and/or ketone reactants. Such
reactions usually give a mixture of multiple condensation products, because there are two
or more possible enolate nucleophiles, and two different carbonyl electrophiles.

Acetone Benzaldehye (E)-4-phenylbut-3-en-2-one

Aldol Condensation Reactions

11
 Retrosynthesis aldol condensation
reaction
β- unsaturated carbonyls can be made from aldol condensation .
The Retrosynthesis of an aldol condensation undergoes the following Steps;
1. Identifying alpha and beta carbons

1. Reversing the dehydration by placing the hydroxyl on the β-carbon and

removing the double bond between the alpha and beta carbon
2. Break the bond existing between the alpha and beta carbons
3. Adding two hydrogen atoms on the alpha carbon and adding an oxygen
atom on the beta carbon and removing the OH group from it.

Aldol Condensation Reactions

12
 Thank you

Questions??

Aldol Condensation Reactions

13