34.3 Amides

Ammonia reacts with an acyl chloride to make a primary amide; a primary amine makes an N-substituted amide. Both are room-temperature condensation reactions with HCl produced.

The nitrogen lone pair attacks the carbonyl carbon and chloride leaves. Use a second equivalent of ammonia or amine to remove the HCl in the overall equation.

CH₃COCl + 2NH₃ → CH₃CONH₂ + NH₄Cl; CH₃COCl + 2CH₃NH₂ → CH₃CONHCH₃ + CH₃NH₃Cl.

Do not count the second base molecule as part of the amide structure; it neutralises the HCl by-product.

Hydrolysis breaks the amide C–N bond. Aqueous acid gives a carboxylic acid and an ammonium ion; aqueous alkali gives a carboxylate salt and ammonia or an amine.

Heating is normally required because the amide is resonance-stabilised. The reaction conditions determine whether the nitrogen product is protonated.

CH₃CONH₂ + H₂O/H⁺ → CH₃CO₂H + NH₄⁺; with aqueous NaOH the products are CH₃CO₂⁻Na⁺ and NH₃.

Do not write the same nitrogen product for acid and alkaline hydrolysis; the acid–base work-up changes its form.

In an amide, the nitrogen lone pair overlaps with the carbonyl π system. Delocalisation gives the C–N bond partial double-bond character and makes the lone pair much less available to accept H⁺ than an amine lone pair.

The carbonyl also withdraws electron density, reinforcing the lower basicity. Protonation is more favourable at oxygen than at nitrogen in many contexts.

An aqueous amine readily forms an ammonium ion, whereas an amide is only weakly protonated under comparable conditions.

Amides still contain a nitrogen lone pair; “weak base” does not mean “no basic behaviour”.