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« Last post by Hunter2 on April 11, 2025, 01:35:12 AM »
Generally Claisen condensation
Ester enolates can be formed with alkoxides, and they are good nucleophiles
Esters can undergo addition-elimination reactions with nucleophiles, otherwise known as nucleophilic acyl substitution. In the Claisen condensation the nucleophile is the ROC(O)CH2 group which displaces (RO-).
Alkoxides can be adequate leaving groups in this case, since they’re significantly weaker bases than ester enolates.
The product of a Claisen condensation is a beta-keto ester, which is a significantly stronger acid (pKa = 11) than either alcohols (pKa = 16-17) or esters (pKa = 25).
The reaction requires at least one equivalent of base since the enolate of the beta-keto ester product is not a strong enough base to deprotonate the starting ester.
A “crossed” Claisen condensation involves the enolate of one ester reacting as a nucleophile with a different (ideally non-enolizable) ester to give a beta-keto ester.
Mixed Claisen condensations are possible if the excess ester does not have protons at C-α. If both esters have α-protons, predominantly statistical mixtures of products can be expected.