Base-Catalyzed Reactions of Carbon Acids

Most aliphatic ketones can lose a proton from either of two carbon atoms adjacent to the carbonyl. The question of which of the possible carbanions or salts is the effective reagent in a given base-catalyzed reaction depends on the nature of the electrophilic reagent with which the ion subsequently reacts. Thus alkyl methyl ketones lose a primary proton in their reactions with alkali and iodine, alkali and an aldehyde, or alkali and carbon dioxide, but lose a secondary proton in certain other reactions. 

Under different conditions, where presumably the reaction with dimethyl sulfate is made fast enough to compete with the back reaction to regenerate the ketone, the product is partly that characteristic of the first mentioned group of reactions in which the rate of proton removal, rather than the amount of salt, controlled the product. 

Base catalyzed condensation reactions of esters and ketones have an additional factor of importance in determining the product, and this is the fact that the overall reaction, as well as the intermediate steps, is highly reversible. The final product may be rate or equilibrium determined, and in the latter case the result may depend on the relative acidity of the various possible products. In a highly basic medium the product will be partly in the form of a salt and the stability of the salt is then a product-determining factor. Failure of a condensation to take place may be due either to an insufficiently high concentration of carbanions or to the instability of the product. The reactions of ethyl isobutyrate will illustrate both points.419 

The success of the reaction with sodium triphenylmethide as a catalyst might have been due to the conversion of the keto ester into a sodio 

The benzoyl derivative is the more rapidly formed, but on standing it is slowly and irreversibly converted into the salt of the isobutyryl derivative. 

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