19.21: Amines to Amides: Acylation of Amines
Various carboxylic acid derivatives (such as acid chlorides, esters, and anhydrides) can be used for the acylation of amines to yield amides. The reaction requires two equivalents of amines. The first amine molecule functions as a nucleophile and attacks the carbonyl carbon to produce a tetrahedral intermediate. This is followed by the loss of the leaving group and restoration of the C=O bond.
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide to a free amide. Amides are stable molecules that are less nucleophilic and basic than amines, making them useful functionalities in electrophilic aromatic substitutions. For instance, the direct bromination of aniline usually results in a tribrominated product as a result of the strongly activating amino group. However, if the amino group is first acylated and then brominated, a monobrominated product can be obtained.
