Preparation and properties

The essentials

Amines can be prepared by reducing nitrogen-containing compounds (nitro compounds, nitriles, amides), by treating alkyl halides with ammonia, by the Gabriel phthalimide synthesis and by the Hoffmann bromamide degradation. Lower aliphatic amines are gases or liquids with a fishy smell; they are soluble in water because they form hydrogen bonds, but solubility falls as the hydrocarbon part grows. Amines are basic because the nitrogen lone pair accepts a proton.

Key points

• Reduction of nitro compounds: H₂/Pd, or Sn/HCl or Fe/HCl. Fe scrap with HCl is preferred industrially.
• Ammonolysis: alkyl halide + NH₃ gives a mixture of 1°, 2°, 3° amines and quaternary salt.
• Nitriles reduced by LiAlH₄ or catalytic hydrogenation give primary amines with one more carbon (chain lengthening). Amides with LiAlH₄ give amines.
• Gabriel synthesis: phthalimide → potassium salt → N-alkylphthalimide → hydrolysis gives a pure 1° amine. It cannot make aromatic amines because aryl halides do not undergo nucleophilic substitution easily.
• Hoffmann bromamide degradation: RCONH₂ + Br₂ + 4NaOH → RNH₂ + Na₂CO₃ + 2NaBr + 2H₂O; the amine has one carbon fewer.
• Boiling points: 1° > 2° > 3° for isomers, because tertiary amines have no N–H for hydrogen bonding.
• Basic strength in water (Kb larger, pKb smaller = stronger base): (CH₃)₂NH > CH₃NH₂ > (CH₃)₃N > NH₃ and (C₂H₅)₂NH > (C₂H₅)₃N > C₂H₅NH₂ > NH₃. The order depends on inductive effect, solvation and steric hindrance.
• Aniline is a much weaker base than ammonia and alkylamines because its lone pair is delocalised into the ring.
• Carbylamine test: 1° amines + CHCl₃ + alcoholic KOH → foul-smelling isocyanide. 2° and 3° amines do not respond.
• Hinsberg's test (benzenesulphonyl chloride): 1° amine gives a sulphonamide soluble in alkali; 2° gives one insoluble in alkali; 3° does not react.
• Aniline with bromine water gives a white precipitate of 2,4,6-tribromoaniline. To get mono-substitution, –NH₂ is first protected by acetylation.
• Direct nitration of aniline gives a large amount of the meta product because in acid aniline is protonated to the meta-directing anilinium ion. Aniline does not undergo Friedel–Crafts reaction.

Common mistakes

• Assuming tertiary amines are always the strongest bases in water; solvation and steric effects change the order.