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Reactions of Carboxylic Acids

Alkylation of Carboxylic Acids in α Position

Similar to carbonyl compounds, the α carbon of carboxylic acids may be deprotonated. The resulting carbanions are good nucleophiles which are utilized in many syntheses, for example in the α alkylation of carboxylic acids.

Due to the higher acidity of the carboxyl hydrogen, two equivalents of a base are required in generating the α carbanion of a carboxylic acid. The base must be considerably strong in order to abstract the α hydrogen. However, the nucleophilicity of the base at the same time be must be as low as possible in order to prevent a nucleophilic attack on the carboxyl carbon. A sufficient base for this reaction is, for instance, lithium diisopropylamide (LDA). LDA is a strong base whose nucleophilicity is relatively low, due to steric reasons.

If a carboxylic acid is treated with LDA, a lithium carboxylate is initially formed. The second equivalent of LDA abstracts the α hydrogen, thus yielding a dianion.

The dianion is a good nucleophile. The most nucleophilic position is the α carbanionic position. The dianion may consecutively nucleophilically attack an electrophile. If the electrophile is a bromine, for instance, α bromination is obtained. Alkylation in α position occurs if an alkyl halide, instead of bromine, is applied. In alkylations, primary alkyl halides offer good results, while with secondary and tertiary alkyl halides, eliminations may occur as side reactions or even as main reactions.

Alkylation and bromination of carboxylic acids in α position.
Example of a carboxylic acid's alkylation in α position.


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