Amines

1. Classification, Naming & Structure

Amines are derivatives of ammonia in which H is replaced by alkyl or aryl groups: 1° (R–NH₂), 2° (R₂NH), 3° (R₃N). Count the carbon groups on nitrogen, not the class of the carbon (that is how alcohols are classified). Simple amines have identical groups, mixed amines have different groups.

Naming. IUPAC: alkane loses –e and gains –amine (CH₃CH₂NH₂ ethanamine, CH₃CH(NH₂)CH₃ propan-2-amine). Substituents on nitrogen use the locant N: CH₃NHCH₂CH₃ is N-methylethanamine; (CH₃)₃N is N,N-dimethylmethanamine. Aromatic: C₆H₅NH₂ is benzenamine (aniline); C₆H₅N(CH₃)₂ is N,N-dimethylbenzenamine.

Structure. Nitrogen is sp³ with a lone pair, so the shape is pyramidal and the C–N–C angle is a little less than 109.5° (108° in trimethylamine). The lone pair is what makes amines basic and nucleophilic.

2. Methods of Preparation

1. Reduction of nitro compounds: H₂/Pd (or Ni, Pt), or Sn/HCl, or Fe/HCl. Fe/HCl is preferred because the FeCl₂ formed hydrolyses and releases HCl, so only a little acid is needed to start.
2. Ammonolysis of alkyl halides: R–X + NH₃ (ethanolic, sealed tube, 373 K) gives a mixture of 1°, 2°, 3° amines and the quaternary salt, because each product is a nucleophile too. A large excess of NH₃ favours the 1° amine. Reactivity RI > RBr > RCl.
3. Reduction of nitriles: LiAlH₄ or H₂/Ni gives R–CH₂NH₂ (adds one carbon, "ascent of the amine series").
4. Reduction of amides: LiAlH₄ gives R–CH₂NH₂ (same carbon count).
5. Gabriel phthalimide synthesis: phthalimide + KOH gives the potassium salt; heat with R–X; alkaline hydrolysis releases the pure 1° aliphatic amine. Aryl halides do not undergo nucleophilic substitution with the phthalimide anion, so aromatic amines cannot be made this way.
6. Hofmann bromamide degradation: R–CONH₂ + Br₂ + 4NaOH → R–NH₂ + Na₂CO₃ + 2NaBr + 2H₂O. The alkyl (or aryl) group migrates from C to N, so the amine has one carbon less. Benzamide gives aniline.

3. Physical Properties

• Lower aliphatic amines are fishy-smelling gases; aniline turns brown on storage (oxidation).
• Boiling point: 1° > 2° > 3° for isomers (1° has two N–H bonds to H-bond, 3° has none). Amines boil higher than alkanes but lower than alcohols of similar mass, because N (3.0) is less electronegative than O (3.5), so N–H···N bonds are weaker than O–H···O. (n-C₄H₉NH₂ 351 K > (C₂H₅)₂NH 329 K > C₂H₅N(CH₃)₂ 311 K; butan-1-ol 390 K.)
• Solubility: lower amines dissolve in water by H-bonding; solubility falls as the alkyl part grows. Butan-1-ol is more soluble than butan-1-amine (more polar, stronger H-bonds).

4. Basic Strength of Amines

Amines are Lewis bases: R–NH₂ + H₂O ⇌ R–NH₃⁺ + OH⁻; larger K_b or smaller pK_b means stronger base. The stronger base forms the more stable cation.

Alkylamines vs ammonia: the +I effect of alkyl groups makes the lone pair more available and stabilises R–NH₃⁺, so alkylamines are stronger than NH₃. In the gas phase the order is 3° > 2° > 1° > NH₃. In water solvation (H-bonding to the cation, 1° > 2° > 3°) and steric hindrance disturb it:

• Methylamines: (CH₃)₂NH > CH₃NH₂ > (CH₃)₃N > NH₃
• Ethylamines: (C₂H₅)₂NH > (C₂H₅)₃N > C₂H₅NH₂ > NH₃

Arylamines vs ammonia: in aniline the lone pair is conjugated with the ring (five resonance structures), while anilinium has only two, so protonation is unfavourable. Aniline is a weaker base than NH₃. On the ring, EDG (–CH₃, –OCH₃) increase basicity and EWG (–NO₂, –SO₃H, –COOH, –X) decrease it: p-toluidine > aniline > p-nitroaniline. Benzylamine (lone pair not in the ring) is stronger than aniline.

Amines form water-soluble ammonium salts with acids; NaOH regenerates the free amine. This separates amines from non-basic organic compounds. Methylamine in water precipitates hydrated Fe₂O₃ from FeCl₃ because it gives OH⁻ (basic).

5. Chemical Reactions of Amines

• Acylation: 1° and 2° amines react with acid chlorides, anhydrides or esters to give amides (H of N–H replaced by acyl), in the presence of a base like pyridine that removes HCl and shifts the equilibrium. Reaction with benzoyl chloride is benzoylation. 3° amines do not react.
• Carbylamine test: only 1° amines (aliphatic or aromatic) with CHCl₃ + alc. KOH, heat, give foul-smelling isocyanides R–NC.
• Nitrous acid (NaNO₂ + HCl): aliphatic 1° amines give alcohols + N₂ (quantitative N₂ is used to estimate amino acids); aromatic 1° amines at 273–278 K give diazonium salts.
• Hinsberg's reagent (C₆H₅SO₂Cl): 1° amine gives a sulphonamide with an acidic N–H, soluble in alkali; 2° gives an alkali-insoluble sulphonamide; 3° does not react.

Electrophilic substitution in aniline. –NH₂ is a very strong o/p-directing activator.

• Bromine water gives a white ppt of 2,4,6-tribromoaniline at once. To get mono-bromo aniline, first acetylate (–NHCOCH₃ is less activating as the N lone pair is in resonance with C=O), brominate, then hydrolyse to p-bromoaniline (major).
• Direct nitration gives oxidation tar plus p (51%), m (47%) and o (2%) products, because in the acid medium aniline is protonated to anilinium (–NH₃⁺), which is meta-directing. Acetylation first gives p-nitroaniline as the major product.
• Sulphonation: aniline + conc. H₂SO₄, heat at 453–473 K gives sulphanilic acid (a zwitterion).
• No Friedel–Crafts: AlCl₃ (Lewis acid) forms a salt with the basic –NH₂, putting a positive charge on N and deactivating the ring.

6. Diazonium Salts

Preparation (diazotisation): C₆H₅NH₂ + NaNO₂ + 2HCl at 273–278 K → C₆H₅N₂⁺Cl⁻ + NaCl + 2H₂O (HNO₂ is made in situ). It is used at once, because it decomposes on warming. Arenediazonium ions are stable in cold solution because of resonance with the ring; alkyldiazonium ions have no such stabilisation and lose N₂ immediately. Benzenediazonium fluoroborate is stable at room temperature and insoluble in water.

Replacement of N₂ (a very good leaving group):

• Sandmeyer: Cu₂Cl₂/HCl, Cu₂Br₂/HBr or CuCN/KCN gives ArCl, ArBr, ArCN. Gattermann: Cu powder with HCl or HBr (lower yield).
• KI gives Ar–I. HBF₄, then heat gives Ar–F. H₃PO₂/H₂O (or ethanol) gives Ar–H. Warm water (283 K) gives phenol. HBF₄, then NaNO₂/Cu, heat gives Ar–NO₂.

Coupling (N₂ group retained): with phenol in alkaline medium at para position gives p-hydroxyazobenzene (orange dye); with aniline in mild acid gives p-aminoazobenzene (yellow dye). It is an electrophilic substitution and the –N=N– group makes extended conjugation, so azo compounds are coloured.

7. Quick Sheet & Last-Minute Checklist

Before the exam, check you can:

• Explain why aniline is weaker than NH₃, and rank amines in water and in the gas phase.
• Write Gabriel and Hofmann, and count carbons correctly in each.
• Distinguish 1°, 2°, 3° amines (Hinsberg, carbylamine) and aniline from ethylamine.
• Explain why aniline gives a meta product on direct nitration and why it fails Friedel–Crafts.
• Convert one compound into another via a diazonium salt (Sandmeyer, Gattermann, coupling).