Claisen ester condensation forced’ reaction

For esters with only one a-hydrogen, such as ethyl 2-methyl propanoate (ethyl isobutyrate), a more powerful base (e.g. sodium triphenylmethide, Ph3CeNa ) is required to affect the condensation reaction [the forced Claisen ester condensation, e.g. the synthesis of ethyl 2,2,4-trimethyl-3-oxopentanoate (ethyl iso-butyrylisobutyrate), Expt 5.176]. In this case the reaction sequence is completed in the step corresponding to (ii) above since the /1-keto ester (24) has no a-hydro-gen for step (iii), and the powerful base is required to force the equilibrium (i) to the right. 

What is the effect of the stoichiometric amount of strong base that allows the Claisen condensation to proceed to completion The /3-ketoester C, which occurs in the equilibrium, is an active-methylene compound and rather C,H-acidic. Therefore, its reaction with the alkoxide to form the ester-substituted enolate D occurs with considerable driving force. This driving force is strong enough to render the deprotonation step C —> D essentially irreversible. Consequently, the overall condensation also becomes irreversible. In this way, all the substrate is eventually converted into enolate D. The neutral /3-ketoester can be isolated after addition of one equivalent of aqueous acid during workup. 

Deprotonation of the /3-keto ester provides a driving force for the Claisen condensation. The deprotonation is strongly exothermic, making the overall reaction exothermic and driving the reaction to completion. Because the base is consumed in the deprotonation step, a full equivalent of base must be used, and the Claisen condensation is said to be base-promoted rather than base-catalyzed. After the reaction is complete, addition of dilute acid converts the enolate back to the /3-keto ester. 

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