[ve_90]

Claisen condensation between cyclohexyl acetate and methyl acetate. Both have alpha hydrogens, so I’m wondering: which one will act as the electrophile and which as the nucleophile? Is it indifferent? I have this doubt in order to understand which mechanism is correct, since, in theory, I could obtain multiple products.

Thank you for your help.

[Hunter2]

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.