12.7 Preparation and Reactions of Amides

Amides are a class of organic compounds derived from carboxylic acids, where the hydroxyl group (–OH) is replaced by an amine group (–NH${}_2$, –NHR, or –NR${}_2$). They can be synthesized through the reaction of acyl chlorides (also known as acid chlorides) with ammonia or primary amines.

1. Preparation of Amides

1.1. From Acyl Chloride with Ammonia

Acyl halides react readily with ammonia at room temperature to produce primary amides. The hydrogen chloride (HCl) generated as a byproduct immediately reacts with any excess ammonia present to form ammonium chloride ($\mathrm{N}{\mathrm{H}}_4\mathrm{Cl}$).

Example reaction: $\underset{\text{Ethanoyl chloride}}{\mathrm{C}{\mathrm{H}}_3\mathrm{COCl}}+2\underset{\text{Ammonia}}{\mathrm{N}{\mathrm{H}}_3}⟶\underset{\text{Ethanamide}}{\mathrm{C}{\mathrm{H}}_3\mathrm{CON}{\mathrm{H}}_2}+\underset{\text{Ammonium chloride}}{\mathrm{N}{\mathrm{H}}_4\mathrm{Cl}}$

1.2. From Acyl Chloride with Primary Amines

Primary amines react similarly to ammonia with acyl chlorides at room temperature, forming N-substituted amides. The hydrogen chloride byproduct reacts with excess amine to form an ammonium salt.

Example reaction: $\underset{\text{Ethanoyl chloride}}{\mathrm{C}{\mathrm{H}}_3\mathrm{COCl}}+\underset{\text{Methylamine}}{\mathrm{C}{\mathrm{H}}_3\mathrm{N}{\mathrm{H}}_2}⟶\underset{\text{N-Methylethanamide}}{\mathrm{C}{\mathrm{H}}_3\mathrm{CONHC}{\mathrm{H}}_3}+\mathrm{HCl}$

1.3. From Carboxylic Acids (Ammonium Salt Method)

Amides can also be prepared by heating the ammonium salts of carboxylic acids. For example, heating ammonium acetate yields acetamide.

2. Reactions of Amides

Amides can undergo various chemical transformations, including reduction and hydrolysis, to yield different functional groups.

2.1. Reduction of Amides

When an amide is treated with a powerful reducing agent, such as lithium aluminium hydride ($\mathrm{LiAl}{\mathrm{H}}_4$), the carbonyl group ($-\mathrm{CO}-$) of the amide is reduced to a methylene group ($-\mathrm{C}{\mathrm{H}}_2-$), resulting in the formation of a primary amine. The carbon chain length remains unchanged during this reaction.

General reaction: $\mathrm{RCON}{\mathrm{H}}_2\stackrel{{\text{1. LiAlH}}_4,{\text{ 2. H}}_2\text{O}}{\to }\mathrm{RC}{\mathrm{H}}_2\mathrm{N}{\mathrm{H}}_2$

Example reaction: $\underset{\text{Ethanamide}}{\mathrm{C}{\mathrm{H}}_3\mathrm{CON}{\mathrm{H}}_2}+2[\mathrm{H}]\stackrel{\mathrm{LiAl}{\mathrm{H}}_4}{\to }\underset{\text{Ethylamine}}{\mathrm{C}{\mathrm{H}}_3\mathrm{C}{\mathrm{H}}_2\mathrm{N}{\mathrm{H}}_2}+{\mathrm{H}}_2\mathrm{O}$

2.2. Hydrolysis of Amides

Amides can be hydrolyzed under both acidic and basic conditions, leading to the cleavage of the amide bond and the formation of carboxylic acids or their salts.

2.2.1. Acid Hydrolysis of Amides

Heating an amide with dilute acids (e.g., dilute hydrochloric acid or dilute sulfuric acid) results in the formation of a carboxylic acid and an ammonium salt.

Example reaction: $\underset{\text{Ethanamide (aq)}}{\mathrm{C}{\mathrm{H}}_3\mathrm{CON}{\mathrm{H}}_2}+{{\mathrm{H}}_2\mathrm{O}}_{(\mathrm{l})}+{\mathrm{HCl}}_{(\mathrm{aq})}⟶\underset{\text{Ethanoic acid (aq)}}{\mathrm{C}{\mathrm{H}}_3\mathrm{COOH}}+\underset{\text{Ammonium chloride (aq)}}{\mathrm{N}{\mathrm{H}}_4\mathrm{Cl}}$

2.2.2. Alkaline Hydrolysis of Amides

Heating an amide with a dilute sodium hydroxide solution leads to the production of a salt of a carboxylic acid and the liberation of ammonia gas. The carboxylic acid salt can then be acidified with dilute hydrochloric acid to yield the free carboxylic acid.

Example reactions: $\underset{\text{Ethanamide (aq)}}{\mathrm{C}{\mathrm{H}}_3\mathrm{CON}{\mathrm{H}}_2}+{\mathrm{NaOH}}_{(\mathrm{aq})}⟶\underset{\text{Sodium ethanoate (aq)}}{\mathrm{C}{\mathrm{H}}_3\mathrm{COONa}}+{\mathrm{NH}}_{3(\mathrm{g})}$ $\underset{\text{Sodium ethanoate (aq)}}{\mathrm{C}{\mathrm{H}}_3\mathrm{COONa}}+{\mathrm{HCl}}_{(\mathrm{aq})}⟶\underset{\text{Ethanoic acid (aq)}}{\mathrm{C}{\mathrm{H}}_3\mathrm{COOH}}+{\mathrm{NaCl}}_{(\mathrm{aq})}$

3. Basicity of Amides

Amides are considerably weaker bases than amines. This difference in basicity stems from the electronic structure of the amido group.

• Electron-Withdrawing Carbonyl Group: The amido group ($-\mathrm{CON}{\mathrm{H}}_2$) contains a highly electronegative carbonyl group ($-\mathrm{C}=\mathrm{O}$) directly adjacent to the nitrogen atom. This carbonyl group withdraws electron density from the nitrogen through two main effects:
  • Resonance Effect: The lone pair of electrons on the nitrogen atom can delocalize into the carbonyl oxygen via resonance. This resonance stabilization makes the nitrogen's lone pair less available for donation to an acid (i.e., less available for protonation). $\mathrm{R}-\stackrel{\mathrm{O}}{\underset{|}{C}}-\mathrm{N}{\mathrm{H}}_2\leftrightarrow \mathrm{R}-\stackrel{{\mathrm{O}}^{-}}{\underset{|}{C}=\mathrm{N}{\mathrm{H}}_2^{+}}$
  • Inductive Effect: The electronegative oxygen atom of the carbonyl group inductively pulls electron density away from the nitrogen atom.
• Reduced Protonation Ability: As a result of these electron-withdrawing and delocalizing effects, the nitrogen atom in amides has significantly reduced electron density and availability of its lone pair. Consequently, amides exhibit a very weak ability to attract and accept a proton (${\mathrm{H}}^{+}$).

In contrast, in amines ($\mathrm{RN}{\mathrm{H}}_2$):

• The lone pair of electrons on the nitrogen is not delocalized by an adjacent carbonyl group.
• Alkyl groups attached to the nitrogen in amines are typically electron-donating, which increases the electron density around the nitrogen atom. This makes the lone pair more available for protonation, explaining why amines are much stronger bases than amides.