Chapter 21: Ester Enolates

Summary

• Ethyl acetoacetate is:
• systematically known as ethyl 3-oxobutanoate
• the Claisen condensation product from ethyl ethanoate (i.e. ethyl acetate) CH₃CO₂CH₂CH₃
• an example of an active methylene compound
• Ethyl acetoacetate is useful because it:
• has a relatively acidic a-proton, pKa = 11, so the enolate is readily formed with ethoxide, EtO^-
• can be readily substituted then hydrolysed and decarboxylated to give a substituted ketone.
• The sequence of reactions:
• Alkylation of an active methylene enolate
• Hydrolysis of an ester to a carboxylic acid
• Decarboxylation of a b-ketoacid
• This process is the equivalent of taking R-X and substituting X with CH₃C=OCH₂-
• In effect, the acyl group of the ester has been used to activate the ketone enolate towards alkylation and has then been removed.
• In principle, both of the a-H can be substituted with alkyl groups and these alkyl groups need not be the same (review)

• Malonic ester synthesis
• Other reactions of enolates

Step 1: First, an acid-base reaction. Ethoxide functions as a base and removes the acidic a-hydrogen giving the reactive enolate which is then alkylated.
Step 2: Acid or base catalysed hydrolysis of the ester to the parent carboxylic acid.
Step 3: Loss of CO2 = decarboxylation, readily occurs giving a substituted ketone.
Mechanisms for the individual steps can be found on the linked pages.