How does the Claisen reaction differ from the aldol reaction?
The Claisen condensation differs from the aldol reaction in several important ways.
(i) The aldol reaction may be catalyzed by acid or base, but most Claisen condensations require base.
(ii) In contrast to the catalytic base used for aldol reactions, a full equivalent of base (or more) must be used for the Claisen condensation. The extra base is needed because beta-ketoesters having acidic hydrogens at the alpha-carbon are stronger acids (by about 5 powers of ten) than the alcohol co-product. Consequently, the alkoxide base released after carbon-carbon bond formation (upper right structure in the mechanism diagram) immediately removes an alpha proton from the beta-ketoester product. As noted above, formation of this doubly-stabilized enolate anion provides a thermodynamic driving force for the condensation.
(iii) The aldol reaction may be catalyzed by hydroxide ion, but the Claisen condensation requires that alkoxide bases be used, in order to avoid ester hydrolysis. The specific alkoxide base used should match the alcohol component of the ester to avoid ester exchange reactions. Very strong bases such as LDA may also be used in this reaction.
(iv) The stabilized enolate product must be neutralized by aqueous acid in order to obtain the beta-ketoester product.
References:
1. Smith, J.; Organic Chemistry; Second Edition; McGraw Hill Co.; Pages 929-930
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