Claisen ester condensation compared to the aldol reaction

Introduction the Claisen ester condensation compared to the aldol reaction  

We began the last chapter with the treatment of acetaldehyde with base. This led initially to the formation of an enolate anion and then to the aldol reaction. We are going to start this chapter with the treatment of ethyl acetate with base, To start with, there is hardly any difference. We shall use ethoxide as base rather than hydroxide as hydroxide would hydrolyse the ester, but otherwise the first steps are very similar. Here they are, one above the other. 

The next step in both cases is nucleophilic attack by the enolate ion on unenolized carbonyl compound. The concentration of enolate is low and each enolate ion is surrounded by unenolized aldehyde or ester molecules, so this reaction is to be expected. Here is that step, again shown for both aldehyde and ester. 

Only now does something different happen, The aldehyde dimer simply captures a proton from the solvent to give an aldol product. The aldof from the ester (not, in fact, an aldol at all) has a leaving group, EtO-, instead of a hydrogen atom and is actually the tetrahedral intermediate in a nucleophilic substitution at the carbonyl group. Compare the two different steps again. 

The point is that the base used, ethoxide ion EtCT, is too weak (EtOH has a pKd of about 16) to remove the proton completely from ethyl acetate (pkTa about 25), but is strong enough to remove a proton from the acetoacetate product (p about 10), Under the conditions of the reaction, a small amount of the enolate of ethyl acetate is produced—just enough to let the reaction happen—but the product is completely converted into its enolate. The neutral product, ethyl acetoacetate itself, is formed on acidic work-up. 

This is another of those reactions where the base is not strong enough to transform the ester entirely into the enolate. Only a small equilibrium concentration fis produced, which reacts with the ester 

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An important reaction of esters is the Claisen condensation, illustrated in reaction (4.30), in which two molecules of an ester react, in the presence of base, to give a P-keto ester. The initial steps of the reaction are similar to the aldol condensation already considered, but because of the lesser acidity of the ester compared with an aldehyde or ketone, a strong base has to be used, and the reaction cannot be carried out in water. 

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