Amines

Amines are organic derivatives of ammonia (NH₃) obtained by replacing one, two, or all three hydrogen atoms of NH₃ by alkyl or aryl groups. Unlike alcohols and haloalkanes — which are classified as primary, secondary or tertiary according to the carbon atom bearing the functional group — amines are classified according to how many hydrogen atoms of NH₃ have been replaced.

• Primary (1°) amine: one H replaced, R–NH₂ (e.g., CH₃NH₂, methanamine)
• Secondary (2°) amine: two H replaced, R–NH–R′ (e.g., (CH₃)₂NH, N-methylmethanamine)
• Tertiary (3°) amine: all three H replaced, R–N(R′)(R″) (e.g., (CH₃)₃N, N,N-dimethylmethanamine)

Amines are further divided into aliphatic amines (only alkyl groups attached to N, e.g., ethanamine) and aromatic amines (at least one aryl group directly bonded to N, e.g., aniline, C₆H₅NH₂). A group such as –CH₂–NH₂ attached to a benzene ring (benzylamine) is still classed as an aliphatic amine because nitrogen itself is bonded to an sp³ carbon, not directly to the ring.

In IUPAC nomenclature, amines are named by adding the suffix -amine to the alkane name (dropping the terminal -e), so CH₃CH₂NH₂ is ethanamine. For secondary and tertiary amines with different groups, the longest carbon chain attached to N is the parent chain, and other substituents are cited with the locant N-; thus CH₃–NH–C₂H₅ is N-methylethanamine, and CH₃–N(CH₃)–C₂H₅ is N,N-dimethylethanamine. Common names (methylamine, dimethylamine, aniline) remain widely used and acceptable.

Worked example: Write all isomeric amines of molecular formula C₃H₉N and classify each.

Using the general formula CₙH₂ₙ₊₃N for a saturated, acyclic amine, n = 3 fits C₃H₉N. The possible structures are:

1. CH₃CH₂CH₂NH₂ — propan-1-amine (n-propylamine) — primary
2. (CH₃)₂CHNH₂ — propan-2-amine (isopropylamine) — primary
3. CH₃–NH–CH₂CH₃ — N-methylethanamine (ethylmethylamine) — secondary
4. (CH₃)₃N — N,N-dimethylmethanamine (trimethylamine) — tertiary

Only isomer 3, N-methylethanamine, is a secondary amine.

Structurally, the nitrogen atom of an amine is sp³ hybridised: three sp³ orbitals form σ bonds to H/C and the fourth holds the lone pair, giving a pyramidal shape with bond angles compressed to about 106°–108° (less than the ideal tetrahedral 109.5°) because lone-pair–bond-pair repulsion exceeds bond-pair–bond-pair repulsion. In aniline, the lone pair on nitrogen is partly delocalised into the benzene ring through resonance, which flattens the pyramid somewhat and gives the C–N bond partial double-bond character; this delocalisation underlies why aromatic amines behave so differently from aliphatic amines in both basicity and ring reactivity (later sections).

Amines can be built up from many different starting materials. The six methods below are prescribed in the current syllabus, and each has a specific strength or limitation worth remembering.

1. Reduction of nitro compounds: Aromatic and aliphatic nitro compounds are reduced to primary amines by catalytic hydrogenation (H₂/Pd or H₂/Ni) or by using Fe/Sn with HCl followed by treatment with NaOH.

C₆H₅NO₂ --(Fe/HCl, then NaOH)--> C₆H₅NH₂

This is the industrial route to aniline from nitrobenzene.

2. Ammonolysis of haloalkanes: Alkyl halides react with excess ammonia (sealed tube, heated) by nucleophilic substitution to give a primary amine, but the primary amine formed is itself nucleophilic and can alkylate further, giving a mixture of 1°, 2°, 3° amines and finally a quaternary ammonium salt.

R–X + NH₃(excess) → R–NH₂ → R₂NH → R₃N → R₄N⁺X⁻

Because the product is a mixture, ammonolysis is a poor method whenever a pure primary amine is required.

3. Reduction of nitriles: Nitriles are reduced by H₂/Ni or LiAlH₄ to give a primary amine with one carbon more than the alkyl halide originally used to make the nitrile — useful for extending a carbon chain while introducing –NH₂.

R–C≡N --(H₂/Ni or LiAlH₄)--> R–CH₂–NH₂

4. Reduction of amides: LiAlH₄ reduces amides to the corresponding amine with the same number of carbons as the amide.

R–CONH₂ --(LiAlH₄)--> R–CH₂–NH₂

5. Gabriel phthalimide synthesis: Phthalimide is treated with ethanolic KOH to form potassium phthalimide, whose nitrogen anion is a good nucleophile. It undergoes SN2 substitution with a primary alkyl halide to give N-alkylphthalimide, which is then hydrolysed (acid, alkaline hydrolysis, or hydrazinolysis) to release the pure primary amine. Because the reaction stops after a single alkylation, this method gives a pure primary amine with no 2°/3° contamination — its main advantage over direct ammonolysis. It cannot make aromatic primary amines, because aryl halides do not undergo nucleophilic substitution with the phthalimide anion.

6. Hofmann bromamide degradation: An amide is treated with bromine in aqueous or ethanolic NaOH. Through an N-bromoamide and a nitrene/isocyanate intermediate (with migration of the R group from carbon to nitrogen), the reaction converts the amide into a primary amine with one carbon less than the starting amide — a chain-shortening route to amines.

R–CONH₂ + Br₂ + 4NaOH → R–NH₂ + 2NaBr + Na₂CO₃ + 2H₂O

Worked example: How would you convert propanamide (CH₃CH₂CONH₂) into ethanamine (CH₃CH₂NH₂)?
Treating propanamide with Br₂ and excess NaOH effects a Hofmann bromamide degradation. The ethyl group migrates from the carbonyl carbon to nitrogen as the carbonyl carbon is lost (eventually as carbonate), so the three-carbon amide is converted cleanly into the two-carbon primary amine, ethanamine, with the ethyl group's configuration retained.

Lower aliphatic amines (methylamine, dimethylamine, trimethylamine) are gases with a characteristic fishy/ammonia-like smell; amines up to about six carbons are volatile liquids, and higher members are solids. Primary and secondary amines have an N–H bond and can form intermolecular hydrogen bonds, but because nitrogen is less electronegative than oxygen, N–H···N hydrogen bonding is weaker than O–H···O bonding in alcohols. For a given carbon number, boiling points follow: alcohol > 1° amine > 2° amine > 3° amine (a tertiary amine has no N–H bond and so cannot hydrogen-bond with itself, giving the lowest boiling point among the three isomeric amines).

Amines of all three classes can hydrogen-bond with water through the lone pair and/or N–H bonds, so lower amines (roughly up to 6 carbons) are fairly soluble in water; solubility falls as the hydrocarbon part grows because the hydrophobic part increasingly dominates. Aniline, despite having an –NH₂ group, is only slightly soluble in water because the large hydrophobic benzene ring outweighs the modest hydrogen-bonding ability of the amino group.

Amines are Lewis bases (and Brønsted bases in water) because of the lone pair on nitrogen, which can accept a proton to form an alkylammonium ion. Base strength is compared using K_b (or pK_b — smaller pK_b means stronger base). Three factors decide amine basicity: (i) the +I effect of alkyl groups, increasing electron density on N and favouring protonation; (ii) steric hindrance around N, hindering protonation and hydration of the cation; and (iii) solvation of the ammonium ion formed — more N–H bonds allow more stabilising hydrogen bonds with water.

In the gas phase, where solvation plays no role, only the inductive effect operates, so basicity increases with alkyl substitution: (CH₃)₃N > (CH₃)₂NH > CH₃NH₂ > NH₃. In aqueous solution, solvation and steric effects compete with the inductive effect, and the regular gas-phase order breaks down. For the methyl series, using the actual pK_b data (methylamine ≈3.38, dimethylamine ≈3.27, trimethylamine ≈4.22, ammonia ≈4.75 — lower pK_b means a stronger base), the observed order of base strength is: (CH₃)₂NH > CH₃NH₂ > (CH₃)₃N > NH₃. The tertiary amine, though it has the greatest +I effect, forms an ammonium ion with only one N–H bond, so it is poorly solvated in water and also suffers steric crowding around nitrogen; both effects pull its aqueous basicity below the primary and secondary amines. Even so, (CH₃)₃N remains a stronger base than plain ammonia, because ammonia has no alkyl (+I) donation at all — so NH₃, not the tertiary amine, ends up the weakest base of the four in water.

Aromatic amines are considerably weaker bases than ammonia or aliphatic amines. In aniline, the lone pair on nitrogen is delocalised into the benzene ring by resonance, making it much less available for protonation; the resulting anilinium ion also loses this resonance stabilisation, making protonation less favourable. Typical pK_b values: methylamine ≈ 3.38, ammonia ≈ 4.75, but aniline ≈ 9.38 — aniline is roughly six orders of magnitude weaker as a base than methylamine.

Substituents on the aniline ring further tune basicity through resonance and induction. Electron-donating groups (–CH₃, –OCH₃) at the para position increase electron density on N and raise basicity (p-toluidine is a stronger base than aniline); electron-withdrawing groups (–NO₂, –X) decrease it, most strongly from the ortho/para position because of direct resonance withdrawal (p-nitroaniline is much weaker than aniline).

Worked example: Arrange aniline, p-nitroaniline and p-toluidine (p-methylaniline) in increasing order of basic strength, with reasoning.
The –NO₂ group at the para position is strongly electron-withdrawing by resonance, pulling electron density away from N and destabilising the anilinium ion, so p-nitroaniline is the weakest base. The –CH₃ group is electron-donating, pushing electron density onto the ring and N, so p-toluidine is the strongest base. Aniline lies in between. Increasing base strength: p-nitroaniline < aniline < p-toluidine.

Because the lone pair on nitrogen makes amines both nucleophilic and basic, they take part in a wide range of reactions — some used as chemical tests to distinguish 1°, 2° and 3° amines, others used to protect or direct reactions on the aromatic ring in aniline.

Alkylation: Amines react with alkyl halides to give progressively more substituted amines and finally a quaternary ammonium salt, exactly as in ammonolysis — a limitation whenever a single, pure product is wanted.

Acylation: Primary and secondary amines react with acid chlorides or acid anhydrides to give N-substituted amides. Aniline reacts with acetic anhydride to give acetanilide:

C₆H₅NH₂ + (CH₃CO)₂O → C₆H₅NHCOCH₃ + CH₃COOH

Acetylation converts the strongly activating –NH₂ group into the more weakly activating –NHCOCH₃ group, used deliberately to moderate aniline's reactivity before electrophilic substitution; the free amine can be regenerated afterwards by hydrolysis of the amide.

Reaction with nitrous acid (HNO₂, generated in situ from NaNO₂ + dilute HCl at 273–278 K) distinguishes the three classes of amine: primary aliphatic amines form an unstable diazonium salt that decomposes immediately with brisk N₂ evolution to give an alcohol; primary aromatic amines (aniline) form a diazonium salt reasonably stable at low temperature (Section 5); secondary amines give a yellow, oily N-nitrosamine; tertiary aliphatic amines merely form an unstable salt with no isolable organic product, while a tertiary aromatic amine such as N,N-dimethylaniline undergoes electrophilic substitution at the ring's para position, giving a green, crystalline p-nitroso compound. This behaviour is used as a qualitative test.

Hinsberg's test (reaction with benzenesulphonyl chloride, C₆H₅SO₂Cl) is the standard method for distinguishing 1°, 2° and 3° amines. A primary amine gives an N-alkylbenzenesulphonamide whose remaining N–H is rendered acidic by the electron-withdrawing –SO₂– group; this product dissolves in aqueous NaOH. A secondary amine gives an N,N-dialkylbenzenesulphonamide with no N–H left, insoluble in NaOH. A tertiary amine has no N–H to begin with, so it does not react and remains an unreacted, water-insoluble amine.

Carbylamine (isocyanide) test: heating any primary amine with chloroform and alcoholic KOH produces a foul-smelling isocyanide; secondary and tertiary amines give no such reaction, making this a specific test for a primary amine.

R–NH₂ + CHCl₃ + 3KOH(alc.) → R–NC + 3KCl + 3H₂O

Electrophilic substitution on the aniline ring: the –NH₂ group is a powerful electron donor by resonance and is strongly ortho, para-directing and activating, making the ring far more reactive than benzene.

• Bromination: aniline reacts instantly with bromine water (no catalyst) to give a white precipitate of 2,4,6-tribromoaniline. To obtain the mono-brominated product, aniline is first acetylated to acetanilide, then brominated (Br₂/ethanoic acid, low temperature) to give predominantly the para isomer, then hydrolysed to give p-bromoaniline as the major product.
• Nitration: direct treatment with concentrated HNO₃/H₂SO₄ is complicated because the strongly acidic medium protonates the amine to the anilinium ion (–NH₃⁺), which is meta-directing and deactivating, giving a mixture of o-, m- and p-nitroaniline plus some tarring. Acetylating first, then nitrating, then hydrolysing gives predominantly p-nitroaniline in a controlled way.
• Sulphonation: aniline heated with concentrated H₂SO₄ forms anilinium hydrogensulphate, which on further heating rearranges to sulphanilic acid (4-aminobenzenesulphonic acid), existing mainly as a zwitterion.

Worked example: Outline, step by step, how p-bromoaniline is obtained from aniline as the major product.
Step 1 — protect the amine: aniline + (CH₃CO)₂O → acetanilide (moderates ring activation, avoiding polysubstitution). Step 2 — brominate: acetanilide + Br₂/CH₃COOH (low temperature) substitutes almost exclusively para to –NHCOCH₃, giving p-bromoacetanilide. Step 3 — deprotect: hydrolysis of the amide converts p-bromoacetanilide back to the free amine, p-bromoaniline.

Aromatic primary amines react with nitrous acid at low temperature to give arenediazonium salts, ArN₂⁺X⁻, containing the characteristic –N≡N⁺ (or Ar–N=N⁺ ↔ Ar–N⁺≡N by resonance) diazonium group bonded to the ring. This reaction, called diazotisation, is carried out by adding sodium nitrite and dilute HCl (or H₂SO₄) to a cold solution of the amine, kept strictly at 273–278 K (0–5 °C):

C₆H₅NH₂ + NaNO₂ + 2HCl --(273–278 K)--> C₆H₅N₂⁺Cl⁻ + NaCl + 2H₂O

The low temperature is essential: diazonium salts are thermally unstable and decompose readily on warming — even in cold aqueous solution they slowly hydrolyse to phenol, and above room temperature (or when dry) many diazonium salts, particularly those of strong acids, decompose vigorously (some explosively). Diazonium salts are therefore almost always prepared fresh, kept cold in solution, and used immediately in the next step rather than isolated and stored.

Benzenediazonium chloride is a colourless, crystalline, water-soluble solid (as normally handled in solution) that is hygroscopic and unstable to heat. Its importance lies in the fact that the diazonium group (–N₂⁺) can be replaced by a wide variety of other groups under mild conditions, or retained to couple with another aromatic ring — both covered in the next section.

Worked example: What mass of NaNO₂ is required to completely diazotise 9.3 g of aniline (molar mass 93 g mol⁻¹)?
Moles of aniline = 9.3 g ÷ 93 g mol⁻¹ = 0.1 mol. Diazotisation consumes NaNO₂ and aniline in a 1:1 mole ratio (see the balanced equation above), so moles of NaNO₂ required = 0.1 mol. Mass of NaNO₂ (molar mass 69 g mol⁻¹) = 0.1 mol × 69 g mol⁻¹ = 6.9 g.

Benzenediazonium salts are among the most versatile intermediates in aromatic synthesis because the –N₂⁺ group can be swapped for many different substituents under conditions difficult or impossible to achieve by direct electrophilic substitution on benzene. These reactions fall into two groups.

(A) Reactions in which N₂ is displaced (replacement reactions):

• Sandmeyer reaction: heating the diazonium salt with cuprous chloride/HCl or cuprous bromide/HBr replaces –N₂⁺ with –Cl or –Br. C₆H₅N₂⁺Cl⁻ + CuCl/HCl → C₆H₅Cl + N₂
• Gattermann reaction: the same halogenation can be carried out using copper powder with HCl or HBr directly, instead of the cuprous halide.
• Iodination: simply treating the diazonium salt with KI (no catalyst) gives the aryl iodide. C₆H₅N₂⁺Cl⁻ + KI → C₆H₅I + N₂ + KCl
• Balz–Schiemann reaction (fluorination): the diazonium chloride is first converted to the diazonium fluoroborate with HBF₄, isolated, and then heated to give the aryl fluoride. C₆H₅N₂⁺Cl⁻ --HBF4--> C₆H₅N₂⁺BF₄⁻ --heat--> C₆H₅F + N₂ + BF₃
• Nitrile formation: heating with CuCN/KCN replaces –N₂⁺ with –CN, giving an aryl nitrile that can be hydrolysed further to an aromatic carboxylic acid. C₆H₅N₂⁺Cl⁻ + CuCN → C₆H₅CN + N₂ + CuCl
• Hydrolysis to phenol: warming the diazonium salt with water (often with dilute H₂SO₄) replaces –N₂⁺ with –OH. C₆H₅N₂⁺Cl⁻ + H₂O --warm--> C₆H₅OH + N₂ + HCl
• Reductive deamination: treating with hypophosphorous acid (H₃PO₂) and water replaces –N₂⁺ with –H, removing the amino group from the ring entirely. C₆H₅N₂⁺Cl⁻ + H₃PO₂ + H₂O → C₆H₆ + N₂ + H₃PO₃ + HCl

(B) Reaction in which the diazo group is retained — coupling reaction: when a diazonium salt reacts with a strongly activated arene (a phenol in weakly alkaline medium, or an aromatic amine in weakly acidic medium), the diazonium ion acts as a weak electrophile and attacks predominantly para to the activating group, forming a brightly coloured azo compound (Ar–N=N–Ar′) linked by an –N=N– bond.

C₆H₅N₂⁺Cl⁻ + C₆H₅OH --(weakly alkaline, cold)--> p-HO-C₆H₄-N=N-C₆H₅ (p-hydroxyazobenzene) + HCl

The extended conjugation through the –N=N– linkage and both rings is responsible for the intense colour of azo compounds.

Taken together, these reactions make the diazonium salt a synthetic junction: starting from an amine, a chemist can install –F, –Cl, –Br, –I, –CN, –OH, or remove the substituent (–H) at a position on the ring fixed by the original nitro/amino group's directing effect — control that direct electrophilic substitution alone often cannot deliver.

Worked example: Starting from benzene, outline a route to fluorobenzene and to iodobenzene.
Benzene is nitrated (conc. HNO₃/H₂SO₄) to nitrobenzene, reduced (Fe/HCl then NaOH, or H₂/Ni) to aniline, then diazotised (NaNO₂/HCl, 273–278 K) to benzenediazonium chloride. For fluorobenzene: convert to the fluoroborate with HBF₄ and heat (Balz–Schiemann) to give C₆H₅F. For iodobenzene: treat the same diazonium chloride with KI to give C₆H₅I directly.