A simplified content on general principle, mechanism and applications of Claisen condensation reaction.

1. CLAISEN CONDENSATION
PRESENTED BY: MR K V NANDA KUMAR
ASSOCIATE PROFESSOR,
KRISHNA TEJA PHARMACY COLLEGE, TIRUPATHI-517506

2. CONTENTS
17-06-2020 PHARM D YEAR I POC - MR K V NANDA KUMAR 2
HISTORY
GENERAL PRINCIPLE
REQUIREMENTS FOR THE REACTION
MECHANISM OF REACTION
EXAMPLES
CROSSED CLAISEN CONDENSATION
INTRAMOLEUCLAR CLAISEN CONDENSATION

3. HISTORY
17-06-2020 PHARM D YEAR I POC - MR K V NANDA KUMAR 3

4. GENERAL PRINCIPLE
The Claisen condensation reaction is an organic coupling reaction that results
in the formation of a C-C bond between either a single ester and one carbonyl
compound or between two esters.
The reaction proceeds when a strong base is present and the product of the
reaction is a beta-keto ester or a beta-diketone.
17-06-2020 PHARM D YEAR I POC - MR K V NANDA KUMAR 4

5. REQUIREMENTS FOR THE REACTION
At least one of the reagents must be enolizable (have an α-proton and be able
to undergo deprotonation to form the enolate anion)
The base used must not interfere with the reaction by undergoing nucleophilic
substitution or addition with a carbonyl carbon.
For this reason, the conjugate sodium alkoxide base of the alcohol formed (e.g.
sodium ethoxide if ethanol is formed) is often used, since the alkoxide is
regenerated.
Another requirement is that the alkoxy part of the ester must behave as a good
leaving group, as in the case of ethyl and methyl esters.
17-06-2020 PHARM D YEAR I POC - MR K V NANDA KUMAR 5

6. MECHANISM OF REACTION
Step 1: Enolate formation
The mechanism of Claisen condensation begins with the formation of the ester
enolate ion.
The ester is first deprotonated in the α position to form a resonance-stabilized
enolate.
17-06-2020 PHARM D YEAR I POC - MR K V NANDA KUMAR 6

7. MECHANISM OF REACTION
Step 2: Nucleophilic
attack
Then this enolate
function as a nucleophile
and attacks another
molecule of the ester,
forming a tetrahedral
intermediate
17-06-2020 PHARM D YEAR I POC - MR K V NANDA KUMAR 7

8. MECHANISM OF REACTION
Step 3: Removal of leaving group
 In the next step, the tetrahedral intermediate expels the leaving group to re-
form a carbon-oxygen double bond.
17-06-2020 PHARM D YEAR I POC - MR K V NANDA KUMAR 8

9. EXAMPLES
17-06-2020 PHARM D YEAR I POC - MR K V NANDA KUMAR 9

10. CROSSED CLAISEN CONDENSATION
Claisen condensations between different ester reactants are
called Crossed Claisen reactions.
17-06-2020 PHARM D YEAR I POC - MR K V NANDA KUMAR 10

11. INTRAMOLECULAR CLAISEN
CONDENSATION
A diester can undergo an intramolecular reaction called a Dieckmann
condensation.
17-06-2020 PHARM D YEAR I POC - MR K V NANDA KUMAR 11

12. FAQ
1. What are the different types of Claisen condensations?
2. What are the key requirements for the Claisen condensation reaction?
3. What is the mechanism of the Claisen condensation reaction?
4. What is the primary difference between Aldol condensation and Claisen
condensation?
5. What are the products formed in Claisen reactions?
17-06-2020 PHARM D YEAR I POC - MR K V NANDA KUMAR 12

13. 17-06-2020 PHARM D YEAR I POC - MR K V NANDA KUMAR 13