Amines: properties, reactions

Organic Chemistry – Amines (Cambridge International AS & A Level, Topic 19)

1. Classification & Systematic Nomenclature

Amines are nitrogen‑containing derivatives of ammonia (NH₃) in which one or more H atoms are replaced by alkyl or aryl groups. The Cambridge syllabus recognises the following classes.

Class	General formula	Typical example	IUPAC name (example)	Key structural feature
Primary (1°)	RNH₂	CH₃NH₂	methanamine	Two N–H bonds
Secondary (2°)	R₂NH	(CH₃)₂NH	N‑methylmethanamine	One N–H bond
Tertiary (3°)	R₃N	(CH₃)₃N	N,N‑dimethylmethanamine	No N–H bond
Aromatic (aryl)	ArNH₂	C₆H₅NH₂ (aniline)	benzenamine	N attached directly to an aromatic ring
Aryl‑alkyl (mixed)	ArNR₂	C₆H₅NHCH₂CH₃	N‑ethyl‑benzenamine	One aryl and one/aliphatic substituent
Branched primary (illustrates naming rule)	RNH₂	(CH₃)₂CHCH₂NH₂	2‑methyl‑1‑propylamine	Longest chain does **not** contain the –NH₂ group

1.1 Systematic IUPAC naming – quick checklist

1. Identify the longest carbon chain that **contains the –NH₂, –NHR or –NR₂ group**. This chain is named as an alkane.
2. Replace the terminal “‑e” of the alkane with “‑amine”. If the nitrogen is attached to a carbon that is not at the end of the chain, give the carbon number (e.g., propan‑1‑amine).
3. If the nitrogen bears alkyl substituents, prefix them with “N‑” and list them alphabetically (e.g., N‑ethyl‑N‑methylpropan‑1‑amine).
4. For aromatic amines the parent name is “benzenamine”. Substituents on the ring are named as normal aromatic prefixes (e.g., 4‑methyl‑benzenamine).

2. Physical & Chemical Properties

2.1 General physical characteristics

• State & odour: Low‑molecular‑weight amines are colourless liquids or gases with a characteristic “fishy” smell.
• VSEPR geometry: The nitrogen atom is sp³‑hybridised; the geometry around N is tetrahedral (≈109.5°) with one lone pair.
• Hydrogen‑bonding:
  • Primary and secondary amines can both donate (via N–H) and accept (via the lone pair) hydrogen bonds → high water solubility.
  • Tertiary amines lack N–H bonds; they can only accept hydrogen bonds, so their water solubility is lower but still appreciable for small molecules.
• Boiling‑point trend:
  • Increases with molecular weight.
  • Within a given carbon count, more N–H bonds (i.e., primary > secondary > tertiary) give higher b.p. because of stronger intermolecular H‑bonding.

2.2 Basicity (pKₐ of the conjugate acid, pK_b of the free base)

Amines (example)	Conjugate‑acid pKₐ (RNH₃⁺)	pK_b (RNH₂)	Comments (syllabus trends)
Methylamine, CH₃NH₂	10.6	3.4	Aliphatic primary – strong base
Diethylamine, (CH₃CH₂)₂NH	10.8	3.2	Secondary – similar to primary
Triethylamine, (CH₃CH₂)₃N	10.7	3.3	Tertiary – steric crowding slightly reduces basicity
Aniline, C₆H₅NH₂	4.6	9.4	Aromatic – lone pair delocalised into the ring
p‑Toluidine, 4‑CH₃C₆H₄NH₂	5.2	8.8	Electron‑donating – slightly stronger than aniline

Key trends (Cambridge aligned)

1. Aliphatic amines are markedly stronger bases than aromatic amines because the nitrogen lone pair is not involved in resonance with a π‑system.
2. Within the aliphatic series: 1° ≈ 2° > 3°. Steric hindrance around nitrogen diminishes the ability to accept a proton.
3. Electron‑donating groups (e.g., –CH₃, –OCH₃) on an aromatic ring increase basicity; electron‑withdrawing groups (e.g., –NO₂) decrease it.

3. Characteristic Reactions of Amines

3.1 Alkylation – Formation of Higher Amines

Amines act as nucleophiles toward alkyl halides. The mechanism depends on the nature of the alkyl halide.

• SN2 (primary or secondary halides) – concerted displacement. Use a polar aprotic solvent (DMF, DMSO) and an excess of the amine to suppress over‑alkylation.
  General equation:
  $$\mathrm{RNH_2 + R'X \xrightarrow{SN2,\;excess\;amine} RNR' + HX}$$
  Example: methylation of methylamine
  $$\mathrm{CH_3NH_2 + CH_3I \rightarrow CH_3NHCH_3 + HI}$$
• SN1 (tertiary halides) – carbocation intermediate. Over‑alkylation is inevitable; mixtures of secondary, tertiary and quaternary amines are usually obtained.

3.2 Acylation – Amide Formation

Amines react with acid chlorides or acid anhydrides to give amides. The reaction is usually carried out at 0 °C – 25 °C with a base (pyridine, Na₂CO₃) to trap the liberated HCl.

$$\mathrm{RNH_2 + R'COCl \xrightarrow{0–25^\circ\mathrm{C}} R'CONHR + HCl}$$

Example: formation of N‑methyl‑acetamide

$$\mathrm{CH_3NH_2 + CH_3COCl \rightarrow CH_3CONHCH_3 + HCl}$$

3.3 Gabriel Synthesis – Preparation of Primary Amines

1. N‑alkylation of potassium phthalimide in DMF:
   $$\mathrm{KPhth + R\!-\!X \rightarrow RPhth + KX}$$
2. Hydrolysis (or hydrazinolysis) of the N‑alkylphthalimide to release the primary amine:
   $$\mathrm{RPhth + H_2O/H^+ \rightarrow RNH_2 + PhthOH}$$

Advantage: no over‑alkylation because the nitrogen is protected as an imide.

3.4 Reductive Amination – Carbonyl → Secondary/Tertiary Amines

One‑pot conversion of aldehydes/ketones to amines.

• Imine (or iminium) formation under mildly acidic conditions (p‑TsOH, AcOH).
  $$\mathrm{R_2C=O + R'NH_2 \xrightarrow{(p\!-\!TsOH)} R_2C=NR' + H_2O}$$
• Reduction of the C=N bond with NaBH₃CN (selective for imines) or H₂/Pd‑C (pH ≈ 5).
  $$\mathrm{R_2C=NR' \xrightarrow{NaBH_3CN} R_2CH–NR'}$$

Result: a secondary amine from a primary amine; using a secondary amine gives a tertiary amine.

3.5 Hofmann Elimination – Alkene from Quaternary Ammonium Salts

Heating a quaternary ammonium hydroxide causes β‑elimination to give the **least‑substituted** (Hofmann) alkene.

$$\mathrm{[R_3N^{+}CH_2CH_2R']X^{-} \xrightarrow{\Delta,\;NaOH} RCH=CH_2 + R'NH_2 + HX}$$

Key points for the syllabus:

• Requires a good leaving group (X⁻) and a strong base.
• The product alkene follows the “Hofmann rule” (least substituted).

3.6 Oxidation of Amines

• Primary aliphatic amines → aldehydes with cold, dilute oxidising agents (KMnO₄, Na₂Cr₂O₇/H⁺). Stronger/hot conditions give nitriles.
  $$\mathrm{RCH_2NH_2 \xrightarrow{[O]} RCHO}$$
• Secondary amines → ketones under the same conditions.
  $$\mathrm{R_2CHNH \xrightarrow{[O]} R_2C=O}$$
• Tertiary amines are generally resistant to oxidation under these reagents.

3.7 Diazotisation of Aromatic Amines

Primary aromatic amines react with nitrous acid (generated in‑situ from NaNO₂/HCl) at 0 – 5 °C to give diazonium salts, which are versatile intermediates.

$$\mathrm{ArNH_2 + HNO_2 + HCl \rightarrow ArN_2^{+}Cl^{-} + 2H_2O}$$

Typical downstream transformations (exam‑relevant)

Reaction	Reagents	Product
Sandmeyer (halogenation)	CuX (X = Cl, Br)	ArX (aryl chloride or bromide)
Sandmeyer (cyanation)	CuCN	ArCN (aryl nitrile)
Reduction	Sn/HCl or H₂/Pd‑C	ArH (aryl hydrocarbon)
Azo coupling	NaNO₂ + NaNO₃, then phenol/aryl‑amine under alkaline conditions	Azo dye (Ar‑N=N‑Ar’)

3.8 Salt Formation (Acid‑Base Extraction)

Amines are basic and readily form water‑soluble ammonium salts with strong acids. This property is exploited for purification.

$$\mathrm{R_3N + HX \rightarrow R_3NH^{+}X^{-}}$$

Typical laboratory work‑up: dissolve the organic mixture in an organic solvent, wash with dilute HCl, separate the aqueous layer (contains the ammonium salt), then basify to regenerate the free amine.

4. Summary of Key Reactions (Quick‑Reference Table)

Reaction type	General equation	Typical conditions	Main product(s)
Alkylation (SN2)	RNH₂ + R'X → RNR' + HX	Polar aprotic solvent, excess amine	Higher amine (primary → secondary, etc.)
Alkylation (SN1)	R₃N + R'X (tert‑alkyl) → mixture of secondary/tertiary/quaternary amines	Reflux, tertiary halide	Over‑alkylated products
Acylation	RNH₂ + R'COCl → R'CONHR + HCl	0–25 °C, base (pyridine, Na₂CO₃)	Amide
Gabriel synthesis	KPhth + RBr → RPhth; RPhth + H₂O/H⁺ → RNH₂ + PhthOH	DMF, then aqueous NaOH or hydrazine	Primary amine
Reductive amination	R₂C=O + R'NH₂ → (iminium) → R₂CH–NR'	NaBH₃CN or H₂/Pd‑C, pH ≈ 5	Secondary (or tertiary) amine
Hofmann elimination	[R₃N⁺CH₂CH₂R']X⁻ → RCH=CH₂ + R'NH₂ + HX	Heat, strong base (NaOH), quaternary ammonium hydroxide	Least‑substituted alkene + secondary amine
Oxidation (primary)	RCH₂NH₂ → RCHO (cold dilute oxidant) or → RCN (hot/strong oxidant)	Cold KMnO₄, Na₂Cr₂O₇/H⁺ (aldehyde); hot/strong for nitrile	Aldehyde or nitrile
Oxidation (secondary)	R₂CHNH → R₂C=O	Same as above	Ketone
Diazotisation	ArNH₂ + NaNO₂/HCl → ArN₂⁺Cl⁻ + 2H₂O	0–5 °C, aqueous acid	Diazonium salt (precursor to Sandmeyer, reduction, azo coupling)
Salt formation (extraction)	R₃N + HX → R₃NH⁺X⁻	Room temperature, aqueous strong acid	Water‑soluble ammonium salt

5. Visual Aids for Classroom Hand‑outs (suggested)

• Structural sketches of primary, secondary and tertiary amines showing N–H bonds, lone pair, and tetrahedral geometry.
• Flow chart of the Gabriel synthesis:
  KPhth → N‑alkylphthalimide → hydrolysis → primary amine.
• Reductive amination pathway diagram: carbonyl → imine/iminium → reduced amine.
• Diazonium‑salt transformations (Sandmeyer, reduction, azo coupling) as a concise decision tree.
• Table of pKₐ values for common amines with a colour‑coded trend bar (strong → weak base).