The acetoacetic ester synthesis is a useful synthetic tool for preparing ketones having one or two alkyl groups on the ɑ position: At first, this may look confusing since there is a whole ester group being lost in the course of the reaction.
In the first part, the ester is hydrolyzed to a carboxylic acid which then loses carbon dioxide through a nicely arranged six-membered transaction state:
The only purpose of the ester group is to make the ɑ hydrogen between the ketones more acidic. Remember, dicarbonyl compounds are about twice more acidic compared to their analogs with only one electron-withdrawing group:
The answer is yes, we can do that, however, having a more acidic ɑ hydrogen allows for using a weaker base and therefore, carrying out the reaction in milder conditions. For example, alkylation of cyclohexanone requires using LDA, while acetoacetic ester can be deprotonated by sodium ethoxide:
A hydroxide base, on the other hand, may hydrolyze the ester to a carboxylic salt before deprotonating the ɑ carbon: Using an alkoxide of a different alkyl group wouldn’t matter in a long run since the ester group is cleaved off at the end anyway:
The alkoxide ion should have the same alkyl group as the ester of the starting β-keto ester. For example, to deprotonate the ethyl acetoacetic ester, an ethoxide salt must be used. If a methoxide or a hydroxide is used, a problem of transesterification occurs: A hydroxide base, on the other hand, may hydrolyze the ester to a carboxylic salt ...