Alkylation of More Stabilized Anions

In both of these cases a carbonyl group(s) is attached to the nucleophilic atom. Resonance delocalization of the electron pair makes the anion more stable. It is easier to generate, and its reactions are easier to control. After the substitution reaction has been accomplished, the carbonyl group(s) is removed, unmasking the desired substitution product. 

Now suppose that we want to use the enolate anion derived from acetone (pKa = 20) as a nucleophile in a substitution reaction. This anion requires the use of a very strong base to generate it, and its high reactivity often causes low yields of the desired product. Instead, we may choose to use its synthetic equivalent, the enolate anion derived from ethyl acetoacetate (pA a =11)  

Alkylation of the enolate anion derived from ethyl acetoacetate followed by removal of the ester group is known as the acetoacetic ester synthesis and is an excellent method for the preparation of methyl ketones. The product of an acetoacetic ester synthesis is the same as the product that would be produced by the addition of the same 

The ester group is removed by treating the alkylated /3-ketoester with aqueous base, followed by treatment with acid and heat  

Let s examine the mechanism of the last part of the acetoacetic ester synthesis, which results in the loss of the ester group. Treatment of the /3-ketoester with aqueous base results in saponification of the ester to form, after acidification, a /3-ketoacid. The mechanism for this step was described in Chapter 19. 

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