Condensation

Amide bond formation between an acid and an amine are formally condensations. The related esterification reactions are governed by equilibrium; however, the mixing of an amine with a carboxylic acid or an acid base reaction forms a stable salt. This means that amide bond formation between these reactants is thermodynamically disfavoured as the equilibrium lies on the side of hydrolysis rather than bond formation, Scheme 1.

Scheme 1: Amide bond formation by reaction of an amine with a carboxylic acid is thermodynamically disfavoured — **Scheme 1:** Amide bond formation by reaction of an amine with a carboxylic acid is thermodynamically disfavoured

The subsequent condensation of the salt to give the amide bond can be achieved at high reaction temperatures ~160-180 °C, which is not only energy demanding, but can also be incompatible in the presence of other functionalities. These forcing reaction conditions have been circumvented by activating the carboxylic acid by using a good leaving group bound to the acyl group of the acid, allowing the necessary attack by the amine group, Scheme 2.

Scheme 2: Amide bond formation through activating of the acyl carbon