Amines: Classification, Structure, and Reactions

🟢 Lite — Quick Review (1h–1d)

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Topic 9 — Key Facts for Kenyatta University (Kenya) Core concept: Amines are organic derivatives of ammonia (NH₃) where one or more hydrogen atoms are replaced by alkyl or aryl groups; they are classified as primary (1°), secondary (2°), or tertiary (3°) based on the number of carbon substituents on the nitrogen atom High-yield point: Basicity order: aliphatic amines > NH₃ > aromatic amines; aniline (C₆H₅NH₂) is much less basic than alkyl amines because the nitrogen lone pair is delocalised into the benzene ring (resonance); the pKb of aniline is ~9.4 vs ~3.3 for ethylamine ⚡ Exam tip: Aromatic amines (aniline) do not react with nitrous acid (HNO₂) to give diazonium salts at room temperature because the diazonium ion is stabilised by the aromatic ring but the reaction is more complex; standard diazotisation requires 0–5°C and gives benzyne-type intermediates

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🟡 Standard — Regular Study (2d–2mo)

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Amines: Organic Nitrogen Compounds

Amines are organic compounds derived from ammonia (NH₃) by replacing one or more hydrogen atoms with an alkyl or aryl group. They are classified based on the number of carbon substituents on the nitrogen atom:

Type	Definition	Structure	Example
Primary (1°)	1 R group attached to N	R–NH₂	Methylamine (CH₃NH₂), Aniline (C₆H₅NH₂)
Secondary (2°)	2 R groups attached to N	R₂NH	Dimethylamine ((CH₃)₂NH), Piperidine (C₅H₁₁N)
Tertiary (3°)	3 R groups attached to N	R₃N	Trimethylamine ((CH₃)₃N), Triethylamine ((C₂H₅)₃N)
Quaternary (4°)	4 R groups attached to N⁺	R₄N⁺	Tetramethylammonium chloride

Note: The 1°/2°/3° classification is based on the number of R groups attached to nitrogen, NOT on the number of hydrogens replaced from NH₃.

Nomenclature

Common names: Alkyl amines follow the pattern “alkylamine” (e.g., ethylamine, propylamine).

IUPAC names:

• Replace the suffix -e of the hydrocarbon with -amine
• e.g., CH₃CH₂NH₂ → Ethanamine
• Position of the –NH₂ group is indicated by the lowest possible number

Aromatic amines (anilines):

• Substituted derivatives are named with the prefix “anilino” or as N-substituted anilines
• N,N-dimethylaniline: C₆H₅N(CH₃)₂

Heterocyclic amines:

• Pyridine: Six-membered aromatic heterocycle with N
• Pyrrole: Five-membered aromatic heterocycle with N
• Piperidine: Saturated six-membered heterocycle with N

Physical Properties of Amines

Boiling Points: Aliphatic amines have boiling points:

• Higher than alkanes of similar molecular weight (due to polarity and hydrogen bonding as donors)
• Lower than alcohols of similar molecular weight (amines can hydrogen bond as donors but not as acceptors of strong hydrogen bonds from other amines)

Hydrogen bonding in amines:

• Primary and secondary amines can hydrogen bond (donor: N–H bond)
• Tertiary amines cannot hydrogen bond (no N–H bond) — this makes 3° amines have lower boiling points than 1°/2° amines of similar MW

Boiling point trends:

Compound	MW	BP (°C)
Trimethylamine	59	3.5
Methylamine	31	−6.3
Dimethylamine	45	7.4
Ethylamine	45	16.6
Propylamine	59	48

Water solubility:

• Small aliphatic amines (C₁–C₃) are completely miscible with water
• Solubility decreases as chain length increases
• Aromatic amines (aniline) are only slightly soluble in water (~3.6 g/100mL at 20°C)

Odour:

• Many low molecular weight amines have a fishy, ammonia-like odour
• Putrescine (H₂N–(CH₂)₄–NH₂): Decayed fish smell
• Cadaverine (H₂N–(CH₂)₅–NH₂): Decayed meat smell
• Coniine (in hemlock): Poisonous alkaloid with mouse-like odour

⚡ Exam Tip: Putrescine and cadaverine are polyamines produced during protein decomposition by bacteria. Their names literally mean “rotting flesh amine” and “decayed meat amine.” This biological context is sometimes used in biochemistry questions.

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🔴 Extended — Deep Study (3mo+)

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Basicity of Amines

Why Amines Are Basic

Amines act as Brønsted-Lowry bases because the nitrogen atom has a lone pair of electrons that can accept a proton (H⁺). When a base (B:) accepts a proton, it becomes its conjugate acid (BH⁺):

R–NH₂ + H⁺ → R–NH₃⁺

The strength of the base depends on how available the lone pair is for protonation.

Basicity of Aliphatic Amines

Aliphatic amines are stronger bases than ammonia because alkyl groups are electron-donating (by hyperconjugation and inductive effects), which increases electron density on nitrogen, making the lone pair more available for protonation.

pKb values (basic strength — lower pKb = stronger base):

Amine	pKb
Methylamine	3.36
Ethylamine	3.30
Dimethylamine	3.27
Diethylamine	3.16
Triethylamine	3.25
Ammonia	4.74

⚡ Exam Tip: The basicity of aliphatic amines is in the order: secondary > primary > tertiary (approximately). Secondary amines are slightly more basic because the second electron-donating alkyl group more than compensates for steric hindrance to solvation. Tertiary amines can be slightly less basic due to steric hindrance.

Basicity of Aromatic Amines

Aniline (C₆H₅NH₂) is a very weak base (pKb ~9.4, pKa of conjugate acid ~4.6), much weaker than ammonia or aliphatic amines.

Reason: The nitrogen lone pair is delocalised into the benzene ring by resonance:

     NH₂          NH₂
      |    ⇌      ||
C₆H₅–N:   →   C₆H₅–N⁺

This resonance stabilisation makes the lone pair less available for protonation. The anilinium ion (C₆H₅NH₃⁺) is less stable because the nitrogen lone pair is less available, making aniline a weaker base.

Substituted anilines:

• Electron-donating groups (–OCH₃, –CH₃) on the benzene ring increase basicity (make the lone pair more available)
• Electron-withdrawing groups (–NO₂, –Cl, –CN) decrease basicity
• para-Nitroaniline is extremely weakly basic (almost neutral)

Basicity of Heterocyclic Amines

Pyridine: Aromatic heterocycle with nitrogen in the ring. The nitrogen lone pair is in an sp² orbital (50% s-character), more tightly held than in aliphatic amines. Pyridine is a moderately weak base (pKb ~8.8), but much stronger than aniline.

Pyrrole: Five-membered aromatic heterocycle with nitrogen. The nitrogen lone pair is part of the aromatic sextet and is NOT available for protonation. Pyrrole is essentially non-basic (pKb ~13.5) — it does not form stable salts with acids.

⚡ Exam Tip: The distinction between pyridine (basic) and pyrrole (non-basic) is a classic exam question. Both are aromatic heterocycles, but the location of the nitrogen’s lone pair determines basicity: in pyridine the lone pair is in a non-bonding orbital (sp²), in pyrrole it is in a bonding orbital contributing to aromaticity.

Reactions of Amines

1. Alkylation

Amines react with alkyl halides via SN2 (primary halides) or SN1 (tertiary halides) to give successively more substituted amines:

R–NH₂ + R'–X → R–NHR' + R'–X → R–NR'₂ + R'–X → R–NR₃⁺X⁻

This is a problem when preparing a single amine product, as a mixture of 1°, 2°, 3°, and 4° products can form.

Gabriel Synthesis: A way to make pure primary amines:

• Phthalimide + KOH → potassium phthalimide
• Potassium phthalimide + R–X (SN2) → N-alkyl phthalimide
• Hydrazine (NH₂NH₂) → releases the primary amine from the phthalimide protecting group

2. Acylation

Amines react with acid chlorides, acid anhydrides, and esters to give amides:

With acid chlorides:

R–NH₂ + R'–COCl → R–CONHR' + HCl   (N-substituted amide)

Primary amine → N-substituted amide (R–CONHR’) Secondary amine → N,N-disubstituted amide (R–CONR’₂)

With acid anhydrides:

R–NH₂ + (R'CO)₂O → R–CONHR' + R'–COOH

With esters:

R–NH₂ + R'–COOR'' → R–CONHR' + R''–OH

⚡ Exam Tip: This acylation reaction is used to “protect” the amino group in peptide synthesis. Acetyl chloride (CH₃COCl) and acetic anhydride are commonly used for acetylation of amines (including aniline).

3. Reaction with Nitrous Acid (HNO₂)

This is a very important reaction that distinguishes primary aliphatic amines from primary aromatic amines:

Primary aliphatic amines + HNO₂:

R–NH₂ + HNO₂ → R–OH + N₂↑ + H₂O

Nitrogen gas is evolved — a qualitative test for primary aliphatic amines. The reaction is violent and the alcohol product is highly carbocation-like, often giving rearranged products.

Primary aromatic amines + HNO₂ (Diazotisation):

C₆H₅NH₂ + HNO₂ + HCl → C₆H₅–N₂⁺Cl⁻ + 2H₂O   (benzenediazonium chloride)

Diazonium salts are formed at 0–5°C. Above 5°C, they decompose to phenol. The diazonium group (–N₂⁺) can be replaced by:

• –OH (warm water): phenol
• –Cl (CuCl/HCl): chlorobenzene
• –Br (CuBr/HBr): bromobenzene
• –CN (CuCN/KCN): benzonitrile
• –I (KI): iodobenzene
• –F (HBF₄): fluorobenzene

⚡ Sandmeyer Reaction: Replacement of the diazonium group by halides or cyanide using Cu catalysts. This is how halogen-substituted benzenes (which cannot be made by direct halogenation of benzene) are prepared.

Secondary amines + HNO₂: Give N-nitrosoamines (yellow oils, often carcinogenic):

(CH₃)₂NH + HNO₂ → (CH₃)₂N–N=O + H₂O   (dimethylnitrosoamine)

Tertiary amines + HNO₂: Tertiary amines undergo elimination or oxidation; aliphatic tertiary amines give N-oxides; aromatic tertiary amines (e.g., N,N-dimethylaniline) give para-nitroso products.

4. Formation of Sulphonamides

Primary amine + benzene sulphonyl chloride (Hinsberg test) → sulphonamide:

R–NH₂ + C₆H₅SO₂Cl → C₆H₅SO₂–NHR + HCl

Hinsberg Test: Used to distinguish 1°, 2°, and 3° amines:

• Primary amine: Gives a sulphonamide that is soluble in alkali (the –SO₂– group is electron-withdrawing, making the N–H acidic)
• Secondary amine: Gives a sulphonamide that is insoluble in alkali
• Tertiary amine: No reaction (no N–H to form sulphonamide)

⚡ Exam Tip: The sulphonamide from a primary amine is soluble because the N–H hydrogen is acidic (due to the electron-withdrawing –SO₂– group) and can be deprotonated by NaOH. This is also the mechanism by which sulfa antibiotics (sulphonamides like sulphanilamide) work — they interfere with folic acid synthesis in bacteria.

5. Hoffmann Elimination

Tertiary amine + excess methyl iodide → quaternary ammonium iodide:

R₃N + CH₃I → R₃N⁺–CH₃ I⁻   (quaternary ammonium salt)

Hofmann Elimination: When heated with Ag₂O (silver oxide) and water, quaternary ammonium hydroxides undergo E2 elimination to give alkenes:

R₃N⁺–CH₃ OH⁻ + heat → R₂C=CR₂ + trimethylamine + H₂O

The least substituted alkene is typically formed (Hofmann product), opposite to Zaitsev’s rule, because the bulky trimethylammonium group is a poor leaving group.

6. Quaternary Ammonium Salts as Phase Transfer Catalysts

Quaternary ammonium salts (e.g., cetyltrimethylammonium bromide, CTAB) are used as phase transfer catalysts because they can transport ionic species (e.g., MnO₄⁻) into organic solvents. This is important for oxidations and other reactions requiring both aqueous and organic phases.

Natural Occurrence of Amines

Amine	Source	Significance
Ammonia	Decomposition of proteins	Industrial chemical
Putrescine	Decaying flesh	Polyamine
Cadaverine	Decaying flesh	Polyamine
Histamine	Allergic response	Vasodilator
Serotonin	Brain (5-HT neurons)	Neurotransmitter
Dopamine	Brain	Neurotransmitter
Adrenaline	Adrenal gland	Fight-or-flight hormone
Aniline	Coal tar	Industrial chemical
Nicotine	Tobacco plant	Alkaloid, stimulant
Morphine	Opium poppy	Analgesic alkaloid
Caffeine	Coffee, tea	Stimulant (methyl xanthine)

⚡ Health Note: Histamine (released during allergic reactions) causes vasodilation, itching, and bronchoconstriction. Antihistamines work by blocking histamine H₁ receptors. Adrenaline (epinephrine) is used as an emergency treatment for anaphylaxis (severe allergic reaction).

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