General Chemistry Principles, Patterns, and Applications, 2011

the two
substituents on the amide nitrogen can be hydrogen atoms, alkyl groups, aryl groups, or any combination of those
species. Although amides appear to be derived from an acid and an amine, in practice they usually cannot be prepared
by this synthetic route. In principle, nucleophilic attack by the lone electron pair of the amine on the carbon of the
carboxylic acid could occur, but because carboxylic acids are weak acids and amines are weak bases, an acid–base
reaction generally occurs instead:
Equation 24.11
RCO 2 H + R′NH 2 → RCO 2 − + R′NH 3
+
Amides are therefore usually prepared by the nucleophilic reaction of amines with more electrophilic
carboxylic acid derivatives, such as esters.
The lone pair of electrons on the nitrogen atom of an amide can participate in π bonding with the carbonyl
group, thus reducing the reactivity of the amide (Figure 24.19 "The Electronic Structure of an Amide")
and inhibiting free rotation about the C–N bond. Amides are therefore the least reactive of the carboxylic
acid derivatives. The stability of the amide bond is crucially important in biology because amide bonds
form the backbones of peptides and proteins. (For more information on peptides and proteins,
see Chapter 12 "Solids", Section 12.8 "Polymeric Solids".) The amide bond is also found in many other
biologically active and commercially important molecules, including penicillin; urea, which is used as
fertilizer; saccharin, a sugar substitute; and valium, a potent tranquilizer. (For more information on the
structure of penicillin, seeChapter 3 "Chemical Reactions", Section 3.2 "Determining Empirical and
Molecular Formulas".)
Note the Pattern
Amides are the least reactive of the carboxylic acid derivatives because amides participate in π bonding
with the carbonyl group.
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