Carboxylic Acids and their Relatives

The use of hydride reagentsfor the reduction of carboxylic acids requires vigorous conditions because the carboxylatc anion, once formed, is resistant to further nucleophilic attack. An interesting exception to this is reduction with borane. A triacyloxyborane may be formed. Re.sonance involving the vacant orbitals of the boron and the lone pairs on the oxygen has the effect of making the attack of a nucleophilic hydride on the carbonyl carbon of the acid easier (see 3.21). 

Acid anhydrides react more easily than the corresponding carboxylic acid with nucleophiles because the electron-withdrawing effect of the second carbonyl group reduces the effect of the lone pairs on the oxygen on the first carbonyl group (see 3.22). 

Once the tetrahedral intermediate has been formed by addition of the nucleophile to a carbonyl, the second carboxyl group acts as a good leaving group, favouring the collapse of the intermediate and the formation of the product. Acid anhydrides are therefore widely used in making the esters of alcohols. 

The carboxylate anion is a useful oxygen nucleophile for the displacement of a variety of leaving groups. A halophilic silver salt may be used for the displacement of a halogen such as an alkyl halide. 

The carboxylate anion may neutralize a carbocation formed by the attack of an electrophilic metal on an alkene, as in the oxymercuration of alkenes. 

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