Revise Amides for Cambridge 9701 (34.3)

Amides are derivatives of carboxylic acids where the hydroxyl (-OH) group has been replaced by an amino (-NH₂) or substituted amino (-NRR') group. The defining feature is the amide functional group, -CONH-. The properties of amides are dominated by the interaction between the nitrogen atom's lone pair and the adjacent carbonyl group.

The lone pair of electrons on the nitrogen atom is delocalised and overlaps with the π-electron system of the carbonyl group. This creates a resonance structure where there is a partial double bond between the carbon and nitrogen atoms. This has two major consequences: firstly, the amide group is planar, as rotation around the C-N bond is restricted. Secondly, because the nitrogen lone pair is delocalised, it is not available to accept a proton, making amides neutral compounds, in stark contrast to the basic nature of amines.

Amides are readily formed by the reaction of acyl chlorides with ammonia, primary amines, or secondary amines. This is a vigorous nucleophilic addition-elimination reaction. As the reaction produces hydrogen chloride (HCl) gas, a second mole of the amine or ammonia is required to act as a base and neutralise it, forming an ammonium salt. Therefore, the stoichiometry is always 1 mole of acyl chloride to 2 moles of amine/ammonia.

Formation of a primary amide (e.g., ethanamide): \ CH₃COCl + 2NH₃ → CH₃CONH₂ + NH₄Cl \ \ Formation of a secondary (N-substituted) amide (e.g., N-methylethanamide): \ CH₃COCl + 2CH₃NH₂ → CH₃CONHCH₃ + CH₃NH₃Cl

The stability of the amide bond means it is resistant to hydrolysis. However, the bond can be broken by prolonged heating under reflux with either a strong acid or a strong alkali. The products depend on the conditions used.

Under acidic conditions (e.g., reflux with dilute H₂SO₄ or HCl), the amide is hydrolysed to a carboxylic acid and an ammonium ion (if a primary amide) or an alkylammonium ion (if an N-substituted amide). The basic nitrogen-containing product is protonated by the excess acid.

Acid Hydrolysis: RCONH₂ + H₂O + H⁺ → RCOOH + NH₄⁺

Under alkaline conditions (e.g., reflux with aqueous NaOH), the amide is hydrolysed to a carboxylate salt and ammonia (or an amine). The acidic carboxylic acid product is deprotonated by the excess alkali.

Alkaline Hydrolysis: RCONH₂ + OH⁻ → RCOO⁻ + NH₃

The formation and hydrolysis of the amide link is central to life itself. Proteins are natural polyamides, formed from amino acid monomers joined by peptide bonds, which are simply amide linkages. Synthetic polyamides, such as Nylon and Kevlar, are also formed by repeating this linkage. This is achieved through condensation polymerisation, typically between a diamine and a dicarboxylic acid (or a diacyl dichloride). The strength and stability of the amide bond contributes to the strength and durability of these materials.