20.4 Amines and Amides

Amines and amides are nitrogen-containing organic compounds that show up constantly in biology and medicine. Amines act as bases and nucleophiles, while amides form the backbone of proteins through peptide bonds. Understanding how these two groups differ in structure, reactivity, and properties is key to connecting organic chemistry to real biological systems.

Amines

Structure and properties of amines

Amines are organic compounds where a nitrogen atom is bonded to one or more carbon atoms. The nitrogen still carries a lone pair of electrons, which drives most of amine chemistry.

Amines are classified by how many carbon atoms are bonded directly to the nitrogen:

• Primary (1°): one carbon bonded to nitrogen (e.g., methylamine, $CH_3NH_2$)
• Secondary (2°): two carbons bonded to nitrogen (e.g., diethylamine)
• Tertiary (3°): three carbons bonded to nitrogen (e.g., triethylamine)

Basicity: That lone pair on nitrogen can accept a proton ($H^+$), forming an ammonium ion ($R-NH_3^+$). This makes amines weak bases in water. In general, the more alkyl groups attached to nitrogen, the more electron density is pushed toward it, which increases basicity. However, the trend isn't perfectly linear because steric effects and solvation also play a role.

Physical properties depend heavily on hydrogen bonding:

• Low molecular weight amines (like ethylamine and propylamine) dissolve well in water because they can hydrogen-bond with water molecules.
• Higher molecular weight amines (like octylamine) become less water-soluble as the hydrocarbon chain dominates.
• Boiling points of amines are higher than similar-sized hydrocarbons but lower than comparable alcohols, since N-H bonds are less polar than O-H bonds.

Amines are also strong nucleophiles because of that nitrogen lone pair, which means they readily attack electrophilic carbon atoms in reactions.

Amides

Formation and characteristics of amides

Amides contain a carbonyl group (C=O) bonded directly to a nitrogen atom. The general formula is $R-CO-NH_2$, $R-CO-NHR'$, or $R-CO-NR'R''$.

How amides form: A carboxylic acid reacts with an amine in a condensation reaction, releasing water. For example:

$CH_3COOH + CH_3NH_2 \rightarrow CH_3CONHCH_3 + H_2O$

(acetic acid + methylamine → N-methylacetamide + water)

Resonance and planarity: The C-N bond in amides has partial double bond character because the nitrogen's lone pair delocalizes into the carbonyl. This resonance makes the amide group planar and restricts rotation around the C-N bond. That restricted rotation is a big deal in protein chemistry.

Basicity: Amides are far less basic than amines. The carbonyl group pulls electron density away from nitrogen through resonance, so the lone pair is much less available to accept a proton. Amides are essentially neutral under normal conditions.

Melting and boiling points are relatively high because amides hydrogen-bond effectively. Acetamide, for instance, melts at 81°C, which is much higher than you'd expect for such a small molecule.

Amines vs amides: comparison

• Functional groups:
  • Amines: nitrogen bonded to carbons and hydrogens ($R-NH_2$, $R-NHR'$, $R-NR'R''$)
  • Amides: nitrogen bonded to a carbonyl carbon ($R-CO-NH_2$, $R-CO-NHR'$, $R-CO-NR'R''$)
• Reactivity:
  • Amines are basic and nucleophilic. They participate in reactions like amide formation (nucleophilic acyl substitution).
  • Amides are much less reactive because resonance stabilizes the C-N bond. However, amides can be broken apart through hydrolysis under acidic or basic conditions, regenerating a carboxylic acid and an amine.
• Biological significance:
  • Amines appear in neurotransmitters like serotonin and dopamine, and in amino acids like lysine and glycine.
  • Amides form the peptide bonds that link amino acids together in proteins. The partial double bond character of the peptide bond is what gives protein backbones their rigidity and stability.
  • Many pharmaceuticals rely on amine or amide groups for their activity. Lidocaine (a local anesthetic) contains an amide linkage, while many antihistamines contain amine groups.