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Reactions of Carboxylic Acids

Reactions with Organolithium Compounds and Metal Hydrides

Carboxylic acids are both Brønsted acids and Lewis acids. Their Lewis acid qualities may be attributed not only to the acidic proton, but also to the electrophilic carbonyl carbon, as they are both able to act as an electron acceptor. However, if a carboxylic acid is treated with an organolithium compound, an acid-base reaction first takes place. In such a reaction, the acidic proton is abstracted by the organolithium compound's alkyl or aryl anion, as alkyl and aryl anions are extremely strong bases. Nevertheless, alkyl and aryl anions are also efficient nucleophiles. As a result, the carbonyl carbon of the carboxylate anion which is formed in the first reaction step is nucleophilically attacked by an additional alkyl or aryl anion. The result of a subsequent hydrolysis is the protonation of the dianion. This yields a geminal diol and lithium hydroxide. The geminal diol represents a ketone's hydrate. Thus, it spontaneously eliminates water to yield the ketone. The reaction may be carried out with primary, secondary, and tertiary alkyllithium compounds, as well as with aryllithium compounds. In order to obtain a ketone in this reaction, two equivalents of the organolithium compound to one equivalent of carboxylic acid must be applied, as the first equivalent is consumed by the acid-base reaction which cannot be prevented.

Fig.1
Reduction of carboxylic acids to ketones with organolithium compounds
Fig.2
Example: Conversion of benzoic acid into t-butyl phenyl ketone by t-butyllithium
Tab.1
3D models of benzoic acid and t-butyl phenyl ketone
Benzoic acidt-Butyl phenyl ketone
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Fig.3
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Fig.4
Fig.5
First step in the reduction of carboxylic acids with organolithium compounds

Due to the negative charge of the carboxylate anion, the electrophilicity of a ketone's carbonyl carbon is comparatively higher. Nevertheless, the ketone does not react with the organolithium compound, as it is not formed until the workup with water through which the remaining organolithium compound is also hydrolyzed.

Fig.6
Second step in the reduction of carboxylic acids with organolithium compounds

In contrast with lithium aluminum hydride, carboxylic acids are reduced to the corresponding primary alcohol.

Fig.7
Reduction of carboxylic acids with lithium aluminum hydride
Fig.8
Example of carboxylic acid's reduction with lithium aluminum hydride
Tab.2
HOOC-(CH)8-COOH HOCH2-(CH)8-CH2OH
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Fig.9
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Fig.10

The mechanism of carboxylic acids' reduction with lithium aluminum hydride is as follows: first of all, an acid-base reaction takes place in which a carboxylate anion is generated, very similar to the reaction with organolithium compounds. The carboxylate anion's carbonyl carbon is then nucleophilically attacked by a hydride that is supplied by the aluminum hydride, while the carbonyl oxygen is complexed by the remaining aluminum species. The following elimination of an oxoaluminum hydride anion yields the aldehyde.

Fig.11
First step of carboxylic acids' reduction with lithium aluminum hydride

The aldehyde's carbonyl carbon is still electrophilic. Thus, it is nucleophilically attacked by a further hydride anion that is supplied by lithium aluminum hydride. Subsequent hydrolysis finally yields the primary alcohol.

Fig.12
Second step of carboxylic acids' reduction with lithium aluminum hydride

Exercises: Reactions with Organolithium Compounds and Metal Hydrides

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