1. Claisen condensation between
Mechanism of the
Claisen condensation between
Ethyl Benzoate and Ethyl Propanoate
Rainer Ludwig Claisen ( )
Developed the “Claisen Condensation” in 1887

3. ETHYL PROPANOATE ETHYL BENZOATE CARBON ETHOXIDE ION HYDROGEN
What are the building blocks?
ETHYL PROPANOATE
ETHYL BENZOATE
CARBON
ETHOXIDE ION
HYDROGEN

4. O O C C C O C C sp2 orbitals p orbitals π bond sp3 orbitals
α hydrogens C C C O C
sp3 orbitals C

5. FORCE & ENERGY O C C Sites for nucleophilic attacks
High Electronegativity of Oxygen
Sites for nucleophilic attacks O C C
α hydrogens

6. Resonance Energy “Stabilization energy”
FORCE &
ENERGY
Resonance Energy “Stabilization energy”

7. Condensation with ethyl benzoate to form β-keto ester
FORCE &
ENERGY
O ||
Formation of the enolate -
Et -O - C - CH – CH3
Condensation with ethyl benzoate to form β-keto ester
Loss of 2nd alpha hydrogen on β-keto ester
Ethyl propanoate
O ||
Et -O - C - CH2 – CH3

8. MATHEMATICS 0.06 0.06 0.14 Ethyl Propanoate 0.04
pKa of alpha hydrogens ≈ 24 or Ka ≈ 10-24
0.06
0.06
0.14
0.04
Ethyl Propanoate

9. MATHEMATICS Bond Angles sp3 orbitals sp2 orbitals 109.5o 120o 90o 180o

10. Overview of the Claisen Condensation Reaction
2. The enolate of ethyl propanoate is formed.
3. The enolate of ethyl propanoate is a strong nucleophile that attacks the partially positive carbon of the carbonyl group on ethyl benzoate.
1. Ethoxide ion acting as a strong base deprotonates ethyl propanoate.
6. The driving force for this reaction is the transfer of the second alpha hydrogen to the ethoxide ion. This is exothermic.
4. The alpha substitution makes this a carbonyl condensation reaction.
Ethyl Propanoate
5. A β-keto ester is formed.
Ethoxide ion
Ethyl Benzoate +

11. Deprotonation of Ethyl Propanoate
The enolate ion is a strong nucleophile and will attack the partially positive carbon of a carbonyl group.
Resonance
Ethyl Benzoate +
Enolate of
Ethyl Propanoate

12. Self condensation of ethyl propanoate

15. Claisen condensation between
Mechanism of the
Claisen condensation between
Ethyl Benzoate and Ethyl Propanoate
Rainer Ludwig Claisen ( )
Developed the “Claisen Condensation” in 1887