Amines

Structure and classification

Amines are primary (RNH_2), secondary (R_2NH) or tertiary (R_3N) depending on how many carbon groups are attached to nitrogen. Quaternary ammonium salts, \mathrm{R_4N^+X^-}, are used as cationic surfactants in fabric softeners. Naming: ethylamine (ethanamine), N-methylethylamine, phenylamine (aniline).

Basicity

The nitrogen lone pair accepts H^+: \mathrm{CH_3NH_2 + H_2O \rightleftharpoons CH_3NH_3^+ + OH^-}. Relative strength:

• Primary aliphatic amines > ammonia: alkyl groups are electron-releasing (positive inductive effect), increasing electron density on N.
• Phenylamine < ammonia: the lone pair overlaps with the benzene π system, so it is less available.

Amines react with acids to form salts, e.g. ethylammonium chloride, which are soluble in water.

Preparation

• Aliphatic amines: heat a halogenoalkane with excess ethanolic ammonia in a sealed tube. The product amine is itself a nucleophile, so further substitution gives secondary and tertiary amines and quaternary salts; excess ammonia limits this. Alternatively, reduce a nitrile with LiAlH_4 or H_2/Ni, which gives only the primary amine (and adds one carbon).
• Aromatic amines: reduce nitrobenzene with tin and concentrated HCl, then add NaOH to liberate phenylamine.

Reactions as nucleophiles

• With halogenoalkanes: successive substitution (mechanism: N lone pair attacks the δ+ carbon).
• With acyl chlorides: vigorous nucleophilic addition–elimination giving N-substituted amides and HCl, e.g. \mathrm{CH_3COCl + 2CH_3NH_2 \rightarrow CH_3CONHCH_3 + CH_3NH_3^+Cl^-}.
• With acid anhydrides: similar, more controllable (used to make paracetamol).

Condensation polymers

Diamines and dicarboxylic acids (or diacyl dichlorides) form polyamides such as nylon-6,6; amide links can be hydrolysed by acid or alkali.

Basicity in detail

Compare pKaH values (pKa of R_3NH^+). Alkyl amines lie near 10–11; in water the order secondary > primary ≈ tertiary reflects induction (favouring more alkyl groups) offset by poorer solvation of R_3NH^+, which has fewer N–H bonds to hydrogen-bond to water. In the gas phase the order is simply 3° > 2° > 1° > NH_3.

Other influences:

• Hybridisation: sp^3 amine (~10) > sp^2 pyridine (5.2) > sp nitrile (very weak).
• Delocalisation: aniline 4.6; para-nitroaniline about 1, because the lone pair conjugates into the nitro group; para-methoxyaniline slightly more basic than aniline.
• Resonance-stabilised conjugate acids: amidines and guanidines (pKaH 12–14) are among the strongest neutral organic bases; DBU is widely used in synthesis.
• Steric hindrance: Hünig's base (iPr_2NEt) is basic but poorly nucleophilic.

Making amines cleanly

Direct alkylation over-alkylates, because each product is more nucleophilic than the starting amine. Better methods:

• Reductive amination: amine + aldehyde/ketone forms an imine or iminium, reduced in situ by NaBH_3CN or NaBH(OAc)_3, which reduce iminium ions faster than carbonyls.
• Gabriel synthesis: potassium phthalimide alkylation then hydrazinolysis gives clean primary amines.
• Reduction of amides, nitriles, azides (Staudinger, or H_2/Pd) and nitro compounds.
• Buchwald–Hartwig Pd-catalysed coupling of aryl halides with amines.

Amide formation

Acid chlorides react rapidly (base such as Et_3N mops up HCl). Directly heating acid and amine gives an unreactive ammonium carboxylate salt, so coupling reagents (DCC, EDC/HOBt, HATU) activate the acid in peptide synthesis. Amides are planar with restricted C–N rotation (partial double bond, barrier around 70–80 kJ mol^{-1}), which shapes protein backbones.

Diazonium chemistry

Primary aryl amines with NaNO_2/HCl below 5 °C form arenediazonium salts via the nitrosonium ion NO^+: N-nitrosation, tautomerisation and loss of water. Aliphatic diazonium ions lose N_2 immediately to give carbocations (and mixtures); aryl diazonium ions are stabilised by conjugation but still decompose above about 5–10 °C.

N_2 is an exceptional leaving group, enabling:

• Sandmeyer (CuCl, CuBr, CuCN; radical mechanism) → ArCl, ArBr, ArCN.
• KI → ArI; HBF_4 then heat → ArF (Balz–Schiemann); warm water → phenol; H_3PO_2 → ArH (removing an amino group after using it to direct substitution).
• Azo coupling: the diazonium ion is a weak electrophile that attacks activated arenes (phenoxides, anilines), usually para, giving coloured azo dyes such as methyl orange.

The strategy "install NH_2, use its directing effect, then replace via diazonium" gives substitution patterns inaccessible by direct electrophilic substitution, e.g. 1,3,5-tribromobenzene from aniline.