Basicity of amines measured by $pK_b$ (or $pK_a$ of conjugate acid, the ammonium salt $RNH_3^+$). Higher $pK_a$ of ammonium = more basic amine. Key factors affecting basicity: (1) Inductive effect (+I) of alkyl groups: alkyl groups donate electrons to N → increased electron density → better proton acceptance → more basic. (2) Resonance (-R) of aryl groups: benzene ring delocalises N lone pair through resonance → reduced electron density on N → less basic. Effect is large: aniline ($pK_a = 4.6$) vs ethylamine ($pK_a = 10.6$). (3) Solvation of ammonium ion in aqueous solution: larger cation (more alkyl groups) may be less well solvated → affects aqueous basicity. This is why tertiary aliphatic amine is slightly less basic than secondary in water despite having most alkyl groups. (4) Steric effect: bulky groups around N may hinder approach of proton. (5) Hybridisation: sp3 N is more basic than sp2 or sp N (electrons held less tightly in sp3 orbital). Pyrrole (N sp2, lone pair in aromatic ring) is non-basic.

Gas phase basicity increases monotonically with alkyl substitution: $R_3N > R_2NH > RNH_2 > NH_3$. Each added alkyl group donates electrons via +I effect. Aqueous solution: different! Secondary amine is most basic (for short alkyl chains). Tertiary is less basic than secondary because: ammonium ion $R_3NH^+$ is poorly solvated (3 bulky alkyl groups block water access to N-H) → less stabilisation of protonated form → less basic. Order in water (for methylamines): $(CH_3)_2NH > CH_3NH_2 > (CH_3)_3N > NH_3$. For ethylamines (this question): $(C_2H_5)_2NH > C_2H_5NH_2 > (C_2H_5)_3N > NH_3$. NEET questions on amine basicity: remember that the aqueous order is 2° > 1° > 3° > NH3 for simple alkylamines (for small alkyl groups). For larger alkyl groups: steric effect on solvation becomes more pronounced.

In aniline (PhNH2), the N lone pair is conjugated with benzene ring: $\text{Ph-NH}_2 \leftrightarrow \text{Ph}^- \text{NH}_2^+$ resonance structures. This partial positive charge on N reduces electron availability → weaker base. pKa values of ammonium salts: NH3: 9.25. CH3NH2: 10.6. (CH3)2NH: 10.7. (CH3)3N: 9.8. PhNH2 (aniline): 4.6. PhN(CH3)H (N-methylaniline): 4.85. Ph2NH (diphenylamine): 0.8. Ph3N (triphenylamine): essentially non-basic. Each additional phenyl group further delocalises lone pair → drastically reduces basicity. Electron-withdrawing groups on ring (NO2, CN) further reduce basicity: p-nitroaniline pKa = 1.0. Electron-donating groups (CH3, OCH3, OH) increase: p-methoxyaniline pKa = 5.3. o-toluidine pKa = 4.44. 2,4-dinitroaniline: pKa = -4.5 (extremely weak base).

Electron-donating groups (EDG): +I alkyl, +R OH, OCH3 → increase electron density on N → increase basicity. Electron-withdrawing groups (EWG): -I halogens, NO2, CN, COOH → decrease electron density → decrease basicity. For N-alkyl aromatic amines: +I of alkyl on N partially offsets -R of phenyl → N-methylaniline slightly more basic than aniline. For amines on ring: EDG on ring → more electron density → ring donates more to N? No: EDG on ring (para) increases electron density in ring → actually decreases the tendency of ring to accept N lone pair → N lone pair less delocalised → more available → more basic. So p-methoxyaniline > aniline > p-nitroaniline. This is because: when ring is electron-rich (EDG), the negative resonance delocalisation from N to ring is less favourable → N retains more electron density.

Pyridine (N in ring, sp2, lone pair in sp2 orbital in plane of ring, NOT in p-orbital): basic ($pK_a = 5.2$). Lone pair available for protonation, not in aromatic system. Pyrrole (N in ring, sp2, lone pair in p-orbital = part of aromatic 6π system): essentially non-basic ($pK_a \approx -3.8$ — lone pair delocalised into aromatic ring, unavailable for protonation). Imidazole: both pyridine-like N (basic, $pK_a = 7.0$) and pyrrole-like N (non-basic). In proteins: histidine has imidazole side chain — $pK_a \approx 6$, important for enzyme catalysis at physiological pH. Quinoline ($pK_a = 4.9$, less basic than pyridine due to extended delocalisation). Piperidine ($pK_a = 11.2$, sp3 N, most basic of common ring amines).

Basic character: react with acids to form ammonium salts (RNH2 + HCl → RNH3+Cl-). Nucleophilic character: react with alkyl halides (SN2, alkylation), acyl halides (amide formation), aldehydes/ketones (imine formation), CO2 (carbamate), NO2+ (nitrosation). Acylation: RNH2 + (CH3CO)2O → RNHCOCH3 (acetamide) + CH3COOH. Protection of amine: acetylation. Benzoylation (Schotten-Baumann, using NaOH). Hinsberg reaction: primary and secondary amines react differently with sulfonyl chloride. Primary amine product is soluble in NaOH (has N-H, acidic). Secondary amine product is insoluble (no N-H). Tertiary amine does not react. Used to distinguish 1°, 2°, 3° amines. Carbylamine reaction: primary amine + CHCl3 + KOH → isocyanide (foul-smelling). Specific to primary amines only.

Industrial amines: Aniline: precursor to dyes (azo dyes, indigo), pharmaceuticals (paracetamol synthesis), polyurethanes (MDI, TDI). Ethylamine: in pharmaceuticals, agricultural chemicals. Hexamethylenediamine + adipic acid → nylon-6,6. Aminoacids: 20 amino acids have amino group. pKa of amino group ≈ 9-10, carboxyl ≈ 2-3 → zwitterion at neutral pH. Neurotransmitters: dopamine, serotonin (5-HT), norepinephrine, epinephrine, histamine, GABA — all amines. Drugs: amphetamine, cocaine, morphine, atropine — all contain amine groups. The amine group can be protonated at physiological pH (positively charged) → important for receptor binding and drug transport across membranes. Drug design: pKa of amine affects membrane permeability (neutral form crosses membranes) and target binding.

From nitro compounds: ArNO2 + Fe/HCl → ArNH2 (aniline from nitrobenzene, industrial method). Also: Sn/HCl, Zn/NH4Cl, H2/Pd catalyst. From nitriles: RCN + H2/Ni → RCH2NH2 (primary amine, one C longer). LiAlH4 also reduces nitriles. Gabriel synthesis: phthalimide + KOH → potassium phthalimide + RX (SN2) → N-alkylphthalimide → hydrolysis (H2O/OH-) → primary amine + phthalic acid. Makes primary amines exclusively (without secondary/tertiary contamination). Hofmann bromamide reaction: RCONH2 + Br2 + NaOH → RNH2 (primary amine, one C SHORTER). Mechanism: N-bromination → ring closure → isocyanate intermediate → hydrolysis. Schmidt reaction: RCOOH + HN3 + H2SO4 → RNH2 (one C shorter). Beckmann rearrangement: ketoxime + H2SO4 → amide.