What are amines?
Amines are derivatives of ammonia in which one or more hydrogen atoms are replaced by alkyl or aryl groups.
Type | Structure | Example |
|---|---|---|
Primary (1°) | R–NH₂ | methanamine CH₃NH₂, aniline C₆H₅NH₂ |
Secondary (2°) | R₂NH | N-methylmethanamine (CH₃)₂NH |
Tertiary (3°) | R₃N | N,N-dimethylmethanamine (CH₃)₃N |
The nitrogen is sp³ hybridised with a lone pair, giving a pyramidal shape. That lone pair makes amines basic and nucleophilic.
Amines occur widely in nature: in proteins, vitamins, alkaloids and hormones such as adrenaline.
Preparation
Reduction of nitro compounds: nitrobenzene with Fe/HCl or H₂/Pd gives aniline. Iron scrap with HCl is preferred industrially, because the FeCl₂ formed is hydrolysed, releasing HCl, so only a little acid is needed.
Ammonolysis of alkyl halides: R–X + NH₃ → R–NH₂ + HX. The product amine reacts further, giving a mixture of 1°, 2° and 3° amines and quaternary ammonium salts. A large excess of ammonia favours the primary amine.
Reduction of nitriles with LiAlH₄ or H₂/Ni gives primary amines with one more carbon (useful for stepping up the chain).
Reduction of amides with LiAlH₄.
Gabriel phthalimide synthesis: phthalimide + KOH gives potassium phthalimide; heating with an alkyl halide and then hydrolysis gives a pure primary aliphatic amine. It can't make aromatic amines, because aryl halides don't undergo nucleophilic substitution with phthalimide anion.
Hofmann bromamide degradation: an amide + Br₂ + NaOH gives a primary amine with one carbon fewer: R–CONH₂ → R–NH₂ (useful for stepping down the chain).
Physical properties
Lower aliphatic amines are gases or volatile liquids with a fishy smell. Primary and secondary amines form hydrogen bonds with each other (tertiary ones can't), so their boiling points follow:
primary > secondary > tertiary (for isomers)
Amines are less hydrogen-bonded than alcohols, because N is less electronegative than O, so they boil lower than alcohols of similar mass. Lower amines are soluble in water.
Basic character
Amines accept protons: R–NH₂ + H₂O ⇌ R–NH₃⁺ + OH⁻. They form salts with acids. A smaller pKb means a stronger base.
Aliphatic amines are stronger bases than ammonia, because alkyl groups push electron density onto the nitrogen (+I effect).
In the gas phase, basicity follows 3° > 2° > 1° > NH₃. In water, solvation of the ammonium ion by hydrogen bonding also matters, and steric hindrance in the 3° amine reduces it. The observed order in water:
for methyl amines: (CH₃)₂NH > CH₃NH₂ > (CH₃)₃N > NH₃
for ethyl amines: (C₂H₅)₂NH > (C₂H₅)₃N > C₂H₅NH₂ > NH₃
Aromatic amines are much weaker bases than ammonia. In aniline, the lone pair on nitrogen is delocalised into the benzene ring by resonance, so it is less available to accept a proton. Electron-donating groups (–CH₃, –OCH₃) on the ring increase basicity; electron-withdrawing groups (–NO₂) decrease it.
Reactions
Alkylation and acylation: amines react with alkyl halides (giving higher amines) and with acid chlorides or anhydrides (giving amides). Acylation of aniline with acetic anhydride gives acetanilide.
Carbylamine reaction (isocyanide test): primary amines (aliphatic and aromatic) heated with chloroform and alcoholic KOH give isocyanides with a very unpleasant smell. Secondary and tertiary amines don't respond. This is a test for primary amines.
R–NH₂ + CHCl₃ + 3KOH → R–NC + 3KCl + 3H₂O
Reaction with nitrous acid (NaNO₂ + HCl, made in the cold):
Primary aliphatic amines give alcohols, with brisk release of nitrogen gas.
Primary aromatic amines at 273–278 K give diazonium salts.
Hinsberg test with benzenesulphonyl chloride (C₆H₅SO₂Cl) distinguishes the three classes:
Amine | Reaction with Hinsberg reagent | Product in alkali |
|---|---|---|
Primary | forms N-alkylbenzenesulphonamide | soluble in alkali (has an acidic H on N) |
Secondary | forms N,N-dialkylbenzenesulphonamide | insoluble in alkali (no H on N) |
Tertiary | no reaction |
Electrophilic substitution of aniline: –NH₂ is a strongly activating, ortho-para directing group.
With bromine water, aniline at once gives a white precipitate of 2,4,6-tribromoaniline.
To get a monosubstituted product, the –NH₂ is first acetylated to reduce its activating effect, then the acetyl group is removed by hydrolysis.
Direct nitration gives a large amount of the meta product too, because in strongly acidic solution aniline is protonated to the anilinium ion, –NH₃⁺, which is meta directing.
Sulphonation gives sulphanilic acid, which exists as a zwitterion.
Aniline does not undergo Friedel-Crafts reactions, because it forms a salt with the AlCl₃ catalyst.
Diazonium salts
Benzenediazonium chloride, C₆H₅N₂⁺Cl⁻, is made by diazotisation: aniline + NaNO₂ + HCl at 273–278 K. It is stable only in the cold, so it is used immediately. Aromatic diazonium salts are more stable than aliphatic ones because of resonance with the ring.
They are very useful for introducing groups onto a benzene ring that can't be added directly.
Replacing the diazo group (N₂ is lost):
Reagent | Product | Name |
|---|---|---|
CuCl/HCl or CuBr/HBr | chlorobenzene / bromobenzene | Sandmeyer reaction |
Cu powder with HCl/HBr | chlorobenzene / bromobenzene | Gattermann reaction |
KI | iodobenzene | |
HBF₄, then heat | fluorobenzene | |
CuCN/KCN | benzonitrile | |
H₃PO₂ or ethanol | benzene | |
warm water | phenol |
Coupling (N₂ is retained): diazonium salts react with phenol (in alkaline solution) or aniline (in mildly acidic solution) at the para position, giving brightly coloured azo compounds, such as orange p-hydroxyazobenzene. These are used as dyes.
Summary
Gabriel synthesis gives pure 1° aliphatic amines; Hofmann bromamide removes one carbon.
Aliphatic amines are more basic than NH₃; aniline is less basic due to resonance.
Carbylamine test: 1° amines only. Hinsberg test: 1° (soluble in alkali), 2° (insoluble), 3° (no reaction).
Diazotisation at 273–278 K gives diazonium salts, which give Sandmeyer products, phenol and azo dyes.