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Also known as: Claisen Ester Condensation
Discovered by Rainer Ludwig Claisen (1887)
The ester analog of the aldol reaction: an ester enolate attacks the carbonyl of another ester molecule, followed by loss of alkoxide to give a β-keto ester. Driven forward by deprotonation of the acidic α-H between the two carbonyls.
Enolate formation: Ethoxide removes an α-hydrogen from the ester to form the ester enolate.
Nucleophilic acyl substitution: The enolate attacks the carbonyl of a second ester molecule, forming a tetrahedral intermediate.
The tetrahedral intermediate collapses, expelling ethoxide to give the β-keto ester product.
Irreversible deprotonation: Ethoxide removes the acidic proton between the two carbonyls (pKa ~11). This drives the equilibrium forward.
Thermodynamic driving force — need full equiv of base
2 Ethyl acetate
NaOEt, EtOH, reflux
Ethyl acetoacetate (acetoacetic ester)
Diethyl adipate (intramolecular)
NaOEt, reflux
2-Carbethoxycyclopentanone (Dieckmann)
Primary route to β-keto esters (1,3-dicarbonyl compounds), which are versatile synthetic intermediates for acetoacetic ester and malonic ester syntheses.