Rainer Ludwig Claisen (1851-1930)

Developed the “Claisen Condensation” in 1887

What are the building blocks?

sp2 orbitals

p orbitalsπ bond

sp3 orbitals

α hydrogens

αα hydrogens hydrogens

Sites for Sites for nucleophilic nucleophilic attacksattacks

High Electronegativity of Oxygen

Resonance Energy“Stabilization energy”

Ethyl propanoate

Formation of the enolate

Condensationwith ethyl

benzoate to form β-keto ester

Et -O - C - CH2 – CH3

O||

Loss of 2nd alpha hydrogen on β-keto ester

Et -O - C - CH – CH3

O|| -

Ethyl Propanoate

0.040.04

pKa of alpha hydrogens ≈ 24 or Ka ≈ 10-24

Bond Angles

120o

sp2 orbitals109.5o

sp3 orbitals

180o

sp orbitals

90o

p orbitals

Overview of the Claisen Condensation Reaction

Ethyl Propanoate

Ethoxide ionEthyl Benzoate

1. Ethoxide ion acting as a strong base deprotonates ethyl propanoate.

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.

4. The alpha substitution makes this a carbonyl condensation reaction.

5. A β-keto ester is formed.

+

6. The driving force for this reaction is the transfer of the second alpha hydrogen to the ethoxide ion. This is exothermic.

Deprotonation of Ethyl Propanoate

ResonanceThe enolate ion is a strong nucleophile and will attack the partially positive carbon of a carbonyl group.

+

Ethyl PropanoateEthyl Propanoate

Ethyl Benzoate

Enolate ofEnolate of

Self condensation of ethyl propanoate

Rainer Ludwig Claisen (1851-1930)

Developed the “Claisen Condensation” in 1887