Amines and Amides: Structure, Properties, and Biological Roles

Chapter 18: Amines and Amides

Introduction

This chapter explores the chemistry of amines and amides, focusing on their structure, classification, physical properties, basicity, reactions, and biological significance, especially in neurotransmission and biochemistry.

Amines: Structure & Classification

Definition and General Structure

• Amines are derivatives of ammonia (NH3) in which one, two, or all three hydrogens are replaced by carbon atoms.

• Amines are classified by the type of carbon-containing groups attached to the nitrogen atom.

Types of Amines

• Aliphatic amines: All carbons bonded to nitrogen are derived from alkyl groups.

• Aromatic amines: At least one carbon bonded to nitrogen is part of an aromatic ring (e.g., aniline).

• Heterocyclic amines: The nitrogen atom is part of a ring system. These are further classified as:

  • Heterocyclic aliphatic amines: Nitrogen is in a non-aromatic ring (primarily C–C single bonds).

  • Heterocyclic aromatic amines: Nitrogen is part of an aromatic ring (includes C=C double bonds).

Examples

• Purines (e.g., adenine, guanine) and pyrimidines (e.g., cytosine, thymine, uracil) are heterocyclic aromatic amines found in nucleic acids.

Physical Properties of Amines

Polarity and Hydrogen Bonding

• Amines are polar compounds due to the presence of the nitrogen atom.

• Both 1o (primary) and 2o (secondary) amines have N–H bonds and can form hydrogen bonds with each other and with water.

• 3o (tertiary) amines lack N–H bonds and cannot form hydrogen bonds with one another, but the nitrogen can still act as a hydrogen bond acceptor.

Solubility and Boiling Points

• Low molecular-weight amines are completely soluble in water.

• Higher molecular-weight amines are moderately soluble or insoluble in water.

• Hydrogen bonding in amines is weaker than in alcohols, resulting in lower boiling points for amines compared to similarly sized alcohols.

Basicity of Amines

General Properties

• Amines are weak bases; aqueous solutions of amines are basic (pH > 7).

• The acid-base reaction between an amine and water involves transfer of a proton from water to the amine, forming a hydroxide anion.

Equilibrium Reaction

• For methylamine: $\text{CH}_3\text{NH}_2 + \text{H}_2\text{O} \rightleftharpoons \text{CH}_3\text{NH}_3^+ + \text{OH}^-$

• At physiological pH (7.2–7.6), amines are typically protonated.

Base Dissociation Constant (Kb)

• The base dissociation constant, Kb, for the reaction of an amine with water is: $\text{K}_b = \frac{[\text{CH}_3\text{NH}_3^+][\text{OH}^-]}{[\text{CH}_3\text{NH}_2]}$

• For methylamine, $\text{K}_b = 4.37 \times 10^{-4}$ and $\text{pK}_b = 3.36$.

• The pKa of methylamine is 10.62.

Physiological Relevance

• In blood (pH ≈ 7.4), amines are mostly in their protonated (conjugate acid) form.

• Example: Dopamine exists predominantly as its conjugate acid in blood.

Reactions of Amines

Salt Formation

• Slightly soluble or insoluble amines react with strong acids to form water-soluble salts.

• Salt formation increases hydrophilicity and solubility, important for pharmaceuticals and natural products.

• Example: $\text{HO–C}_6\text{H}_4\text{–NH}_2 + \text{HCl} \rightarrow \text{HO–C}_6\text{H}_4\text{–NH}_3^+ \text{Cl}^-$

Quaternary Amines

Structure and Properties

• In quaternary ammonium salts, nitrogen is bound to four carbon groups, carrying a formal +1 charge.

• Quaternary amines do not have a pKa because they cannot accept or donate a proton.

• Example: Choline and tetramethylammonium chloride.

Neurotransmitters

Role and Mechanism

• Neurotransmitters are compounds that transmit nerve impulses between cells.

• They are released at synapses and bind to receptors on target cells.

• Many neurotransmitters are amines, including acetylcholine and catecholamines (derived from amino acids).

Clinical Relevance

• Improper neurotransmitter production can result in diseases such as Parkinson's disease (decreased dopamine).

• Treatment may include L-dopa, a precursor for dopamine production.

Neurotransmitters Derived from Amino Acids

Amino Acid	Neurotransmitter	Function
Tyrosine	Dopamine, Norepinephrine, Epinephrine	Motor control, mood, stress response
Glutamate	GABA	Inhibitory neurotransmission
Serine	Glycine	Inhibitory neurotransmission
Histidine	Histamine	Immune response, gastric secretion
Additional info: Table inferred from slide and standard biochemistry sources.

Amides

Structure and Types

• The functional group of an amide is a carbonyl group bonded to a nitrogen atom: $\text{R–CO–NH}_2$

• Cyclic amides are called lactams.

Preparation of Amides

Methods

• Amides can be synthesized by treating a carboxylic acid with an amine (similar to Fischer esterification), but this reaction is slow due to acid/base properties.

• Amide formation can be accelerated by raising the temperature.

• A more common method is to react an amine with an anhydride: $\text{(RCO)}_2\text{O} + \text{R'NH}_2 \rightarrow \text{RCONHR'} + \text{RCOOH}$

• This method is faster and more favorable due to increased reactivity of anhydrides.

Lactams (Cyclic Amides)

Biological Importance

• Lactams are found in antibiotics such as penicillin and cephalosporins.

• These compounds inhibit enzymes (proteins) involved in bacterial cell wall synthesis.

Summary Table: Amines vs. Amides

Property	Amines	Amides
Functional Group	NH2, NHR, NR2	CONH2, CONHR, CONR2
Basicity	Weak bases	Neutral or weakly basic
Hydrogen Bonding	Yes (1o, 2o amines)	Yes
Solubility	Variable (depends on size)	Generally good (small amides)
Biological Role	Neurotransmitters, drugs	Proteins, antibiotics

Additional info: Table constructed for comparison based on standard chemical properties.