Organic Compounds Containing Nitrogen (Amines & Diazonium Salts)

1. Structure, Classification & Nomenclature

• Electronic Geometry: Nitrogen is $sp^3$-hybridised with a trigonal pyramidal shape. The unshared electron pair occupies the fourth hybrid orbital, compressing the $\text{C}-\text{N}-\text{C}$ bond angle to $108^\circ$ (e.g., trimethylamine) due to lone pair-bond pair repulsion.
• Classification Framework:
  • Primary ($1^\circ$): One hydrogen of ammonia replaced by an alkyl/aryl group ($\text{R}-\text{NH}_2$).
  • Secondary ($2^\circ$): Two hydrogens replaced ($\text{R}_2\text{NH}$ or $\text{R}-\text{NH}-\text{R}'$).
  • Tertiary ($3^\circ$): All three hydrogens replaced ($\text{R}_3\text{N}$).
  • Quaternary Ammonium Salts: Tetra-alkylated nitrogen cations ($\text{R}_4\text{N}^+\text{X}^-$) used as cationic surfactants.
• IUPAC Nomenclature: Aliphatic amines are named as alkanamines by replacing the final 'e' of the alkane name with 'amine' (e.g., $\text{CH}_3\text{CH}_2\text{NH}_2$ is ethanamine). In secondary and tertiary amines, substituents on nitrogen take the locant prefix $N$ (e.g., $N$-methylethanamine, $N,N$-dimethylaniline).

2. Preparative Routes: Reduction, Gabriel & Hoffmann

• Reduction of Nitrogenous Precursors:
  • Nitro Compounds: Catalytic hydrogenation over $\text{Pd}/\text{Pt}$ or reduction with metals in acid:

$$\text{Ar-NO}_2 + 3\text{Fe} + 6\text{HCl} \longrightarrow \text{Ar-NH}_2 + 3\text{FeCl}_2 + 2\text{H}_2\text{O}$$

$\text{Fe} + \text{HCl}$ is preferred industrially because the generated $\text{FeCl}_2$ hydrolyses to regenerate $\text{HCl}$, requiring only catalytic acid initiation.

• Nitriles (Mendius Reduction): Reduction with $\text{LiAlH}_4$ or $\text{Na(Hg)}/\text{EtOH}$ yields primary amines with one additional carbon:

$$\text{R-C}\equiv\text{N} \xrightarrow{\text{LiAlH}_4} \text{R-CH}_2-\text{NH}_2$$

• Amides: $\text{R-CONH}_2 \xrightarrow{\text{(i) }\text{LiAlH}_4\text{, (ii) }\text{H}_2\text{O}} \text{R-CH}_2-\text{NH}_2$.
• Gabriel Phthalimide Synthesis: Potassium phthalimide undergoes nucleophilic $\text{S}_\text{N}2$ displacement with primary alkyl halides, followed by alkaline hydrolysis to yield pure primary aliphatic amines:

$$\text{Phthalimide} \xrightarrow{\text{KOH}} \text{Potassium Phthalimide} \xrightarrow{\text{R-X}} N\text{-Alkylphthalimide} \xrightarrow{\text{aq. NaOH}} \text{Sodium Phthalate} + \text{R-NH}_2$$

Aromatic primary amines cannot be prepared this way because aryl halides resist nucleophilic substitution by the phthalimide anion.

• Hoffmann Bromamide Degradation: Primary amides react with bromine in aqueous or ethanolic $\text{NaOH}$ to yield primary amines with one less carbon atom:

$$\text{R-CONH}_2 + \text{Br}_2 + 4\text{NaOH} \longrightarrow \text{R-NH}_2 + \text{Na}_2\text{CO}_3 + 2\text{NaBr} + 2\text{H}_2\text{O}$$

3. Physical Properties & The Basicity Paradox

• Physical State & Boiling Points: Lower aliphatic amines are gases with a fishy odour. Boiling points follow the order: $1^\circ\text{ Amine} > 2^\circ\text{ Amine} > 3^\circ\text{ Amine}$, because $1^\circ$ amines form two intermolecular hydrogen bonds, $2^\circ$ form one, and $3^\circ$ amines lack $\text{N}-\text{H}$ bonds entirely.
• Gas Phase Basicity: In the absence of solvent, basic strength is governed entirely by the $+I$ inductive electron push of alkyl groups:

$$\text{Gas Phase: } 3^\circ\text{ Amine} > 2^\circ\text{ Amine} > 1^\circ\text{ Amine} > \text{NH}_3$$

• Aqueous Phase Basicity Paradox: In water, basicity is governed by an interplay of three opposing factors: inductive effect ($+I$), steric hindrance, and stabilization of the conjugate ammonium cation by hydrogen-bonded solvation:
  • Ethyl series: $(\text{C}_2\text{H}_5)_2\text{NH} > (\text{C}_2\text{H}_5)_3\text{N} > \text{C}_2\text{H}_5\text{NH}_2 > \text{NH}_3$ ($2^\circ > 3^\circ > 1^\circ > \text{NH}_3$).
  • Methyl series: $(\text{CH}_3)_2\text{NH} > \text{CH}_3\text{NH}_2 > (\text{CH}_3)_3\text{N} > \text{NH}_3$ ($2^\circ > 1^\circ > 3^\circ > \text{NH}_3$).
• Arylamines Basicity: Aniline ($\text{p}K_b = 9.38$) is weaker than ammonia ($\text{p}K_b = 4.75$) due to resonance delocalization of the nitrogen lone pair into the ring. Electron-donating groups ($-\text{OCH}_3, -\text{CH}_3$) increase basicity, whereas electron-withdrawing groups ($-\text{NO}_2, -\text{CN}, -\text{X}$) decrease it.

4. Chemical Reactions: Acylation & Carbylamine Test

• Acylation & Benzoylation (Schotten-Baumann Reaction): Primary and secondary amines react with acid chlorides or anhydrides in the presence of pyridine to form substituted amides. Pyridine removes the formed $\text{HCl}$, driving equilibrium forward:

$$\text{C}_2\text{H}_5\text{NH}_2 + \text{CH}_3\text{COCl} \xrightarrow{\text{Pyridine}} \text{C}_2\text{H}_5\text{NHCOCH}_3 + \text{HCl}$$

• Carbylamine Test (Isocyanide Test for $1^\circ$ Amines): Primary aliphatic and aromatic amines on heating with chloroform and ethanolic $\text{KOH}$ produce foul-smelling isocyanides:

$$\text{R-NH}_2 + \text{CHCl}_3 + 3\text{KOH} \xrightarrow{\Delta} \text{R-NC}\ (\text{Carbylamine}) + 3\text{KCl} + 3\text{H}_2\text{O}$$

Secondary and tertiary amines do not undergo this reaction.

5. Hinsberg Test & Nitrous Acid Differentiation

• Hinsberg Reagent ($\text{C}_6\text{H}_5\text{SO}_2\text{Cl}$):
  • Primary Amines: Form $N$-alkylbenzenesulphonamide, which contains an acidic hydrogen on nitrogen and dissolves in aqueous $\text{KOH}$.
  • Secondary Amines: Form $N,N$-dialkylbenzenesulphonamide, which lacks an acidic hydrogen and remains insoluble in alkali.
  • Tertiary Amines: Do not react under Hinsberg conditions.
• Reaction with Nitrous Acid ($\text{HNO}_2$ generated in situ):
  • Primary Aliphatic Amines: Form highly unstable alkyldiazonium salts that decompose into alcohols, alkenes, and alkyl halides, liberating nitrogen gas quantitatively:

$$\text{R-NH}_2 + \text{HNO}_2 \xrightarrow{\text{NaNO}_2 + \text{HCl}} [\text{R-N}_2^+\text{Cl}^-] \xrightarrow{\text{H}_2\text{O}} \text{R-OH} + \text{N}_2\uparrow + \text{HCl}$$

• Primary Aromatic Amines: Form stable arenediazonium salts at low temperatures (273-278 K).
• Secondary Amines: Form yellow oily $N$-nitrosamines.

6. Ring Electrophilic Substitutions of Aniline

• Halogenation: Due to the strong activation of the $-\text{NH}_2$ group, aniline reacts with bromine water at room temperature to give an immediate white precipitate of 2,4,6-tribromoaniline:

$$\text{C}_6\text{H}_5\text{NH}_2 + 3\text{Br}_2\ (\text{aq}) \longrightarrow \text{2,4,6-Tribromoaniline}\downarrow + 3\text{HBr}$$

To obtain monobromoaniline, the amino group must be protected by acetylation with acetic anhydride before bromination, followed by ester/amide hydrolysis.

• Nitration: Direct nitration yields a mixture of products: $51\%\ p\text{-nitroaniline}$, $47\%\ m\text{-nitroaniline}$, and $2\%\ o\text{-nitroaniline}$. The high meta yield is due to protonation of aniline in strong acid to form the meta-directing anilinium ion.
• Sulphonation: Heating anilinium hydrogensulphate at 453-473 K gives sulphanilic acid, which exists as a dipolar zwitterion:

$$\text{C}_6\text{H}_5\text{NH}_2 + \text{conc. H}_2\text{SO}_4 \longrightarrow \text{C}_6\text{H}_5\text{NH}_3^+\text{HSO}_4^- \xrightarrow{453-473\text{ K}} p\text{-H}_3\text{N}^+-\text{C}_6\text{H}_4-\text{SO}_3^-\ (\text{Zwitterion})$$

7. Diazonium Salts: Preparation & Synthetic Hub

• Diazotisation Mechanism: Primary aromatic amines react with $\text{NaNO}_2 + 2\text{HCl}$ at 273-278 K ($0-5^\circ\text{C}$) to form benzenediazonium chloride:

$$\text{C}_6\text{H}_5\text{NH}_2 + \text{NaNO}_2 + 2\text{HCl} \xrightarrow{273-278\text{ K}} \text{C}_6\text{H}_5\text{N}_2^+\text{Cl}^- + \text{NaCl} + 2\text{H}_2\text{O}$$

• Displacement Reactions of Nitrogen:
  • Sandmeyer Reaction: $\text{Ar-N}_2^+\text{Cl}^- \xrightarrow{\text{Cu}_2\text{X}_2/\text{HX}} \text{Ar-X} + \text{N}_2\uparrow \quad (\text{X} = \text{Cl, Br, CN})$.
  • Gattermann Reaction: $\text{Ar-N}_2^+\text{Cl}^- \xrightarrow{\text{Cu}/\text{HX}} \text{Ar-X} + \text{N}_2\uparrow + \text{CuCl}$.
  • Iodination: $\text{Ar-N}_2^+\text{Cl}^- + \text{KI}\ (\text{warm}) \longrightarrow \text{Ar-I} + \text{KCl} + \text{N}_2\uparrow$.
  • Balz-Schiemann Reaction: $\text{Ar-N}_2^+\text{Cl}^- + \text{HBF}_4 \longrightarrow \text{Ar-N}_2^+\text{BF}_4^- \xrightarrow{\Delta} \text{Ar-F} + \text{BF}_3 + \text{N}_2\uparrow$.
  • Deamination: $\text{Ar-N}_2^+\text{Cl}^- + \text{H}_3\text{PO}_2 + \text{H}_2\text{O} \longrightarrow \text{Ar-H} + \text{N}_2\uparrow + \text{H}_3\text{PO}_3 + \text{HCl}$.
  • Hydrolysis: Warming with water above 283 K forms phenol: $\text{Ar-N}_2^+\text{Cl}^- + \text{H}_2\text{O} \longrightarrow \text{Ar-OH} + \text{N}_2\uparrow + \text{HCl}$.
• Azo Coupling Reactions: Diazonium salts act as electrophiles and couple with activated aromatic compounds:
  • With Phenol (mildly alkaline, $\text{pH } 9-10$): Yields $p$-hydroxyazobenzene (orange dye).
  • With Aniline (mildly acidic, $\text{pH } 4-5$): Yields $p$-aminoazobenzene (yellow dye).