🕊️ Amines & Nitrogen Compounds

Nitrogen compounds showcase lone-pair basicity, nucleophilicity, and the versatile synthetic power of aryldiazonium salts ($Ar-N_2^{+}{X}^{-}$). High-yield exam topics include aliphatic vs aromatic amine basicity, Gabriel phthalimide limitations, Hoffmann bromamide retention of stereochemistry, and Sandmeyer vs Gattermann vs Azo dye coupling.

---

1. 🧪 Synthesis of Primary Amines

1.1 Gabriel Phthalimide Synthesis

$$\text{Phthalimide}\stackrel{KOH}{\to }\text{Potassium Phthalimide}\stackrel{R-X(S_{N}2)}{\to }N\text{-Alkylphthalimide}\stackrel{H_3{O}^{+}\text{ or }N{H}_{2}N{H}_2}{\to }\mathbf{R}\mathbf{-}{\mathbf{NH}}_{\mathbf{2}}\mathbf{(}\text{Pure }{\mathbf{1}}^{\circ }\text{ aliphatic amine}\mathbf{)}$$

• Major Limitation: Aromatic $1^{c}irc$ amines (Aniline) CANNOT be prepared by this method because aryl halides do not undergo nucleophilic substitution ($S_{N}2$) with phthalimide anion!

1.2 Hoffmann Bromamide Degradation Reaction

Conversion of $1^{c}irc$ acid amide into $1^{c}irc$ amine containing one less carbon atom:

$$R-CON{H}_2+B{r}_2+4KOH\stackrel{\mathrm{\Delta }}{\to }\mathbf{R}\mathbf{-}{\mathbf{NH}}_{\mathbf{2}}\mathbf{+}{\mathbf{K}}_{\mathbf{2}}{\mathbf{CO}}_{\mathbf{3}}\mathbf{+}\mathbf{2}\mathbf{KBr}\mathbf{+}\mathbf{2}{\mathbf{H}}_{\mathbf{2}}\mathbf{O}$$

• Intermediate Involved: Alkyl Isocyanate ($R-N=C=O$).
• Stereochemistry: The migration of alkyl/aryl group $R$ from carbonyl carbon to nitrogen proceeds with 100% retention of configuration at the migrating chiral center!

---

2. 🔍 Distinction of $1^{c}irc,2^{c}irc,3^{c}irc$ Amines: The Hinsberg Test

$$\text{Reagent: Benzene Sulfonyl Chloride }(Ph-S{O}_{2}Cl)$$

• $1^{c}irc$ Amine ($R-N{H}_2$): Forms $N$-alkyl benzene sulfonamide ($Ph-S{O}_{2}NHR$), which contains an acidic hydrogen attached to nitrogen $implies$ Soluble in aqueous $KOH$. Acidification precipitates it back.
• $2^{c}irc$ Amine ($R_{2}NH$): Forms $N,N$-dialkyl benzene sulfonamide ($Ph-S{O}_{2}N{R}_2$), which has no acidic hydrogen on nitrogen $implies$ Insoluble in aqueous $KOH$.
• $3^{c}irc$ Amine ($R_{3}N$): Has no replaceable hydrogen on nitrogen $implies$ Does NOT react with Hinsberg reagent.

---

3. 🌈 Aryl Diazonium Salts ($Ar-N_2^{+}C{l}^{-}$) & Synthetic Transformations

Preparation by Diazotization:

$$Ph-N{H}_2+NaN{O}_2+2HCl\stackrel{0-5^{\circ }\text{C}}{\to }\mathbf{Ph}\mathbf{-}{\mathbf{N}}_{\mathbf{2}}^{\mathbf{+}}{\mathbf{Cl}}^{\mathbf{-}}\mathbf{+}\mathbf{NaCl}\mathbf{+}\mathbf{2}{\mathbf{H}}_{\mathbf{2}}\mathbf{O}$$

Key Reactions of Benzene Diazonium Chloride:

• Sandmeyer Reaction ($CuCl/HCl,CuBr/HBr,CuCN/KCN$): Yields Chlorobenzene, Bromobenzene, Benzonitrile.
• Gattermann Reaction ($Cu/HCl,Cu/HBr$): Yields Chlorobenzene, Bromobenzene.
• Schiemann Reaction ($HB{F}_4,\mathrm{\Delta }$): Yields pure Fluorobenzene ($Ph-F$).
• Replacement by Iodide ($KI,\text{warm}$): Yields Iodobenzene ($Ph-I$).
• Reduction to Benzene: Using Hypophosphorous acid ($H_{3}P{O}_2+H_{2}O$) or Ethanol ($C{H}_{3}C{H}_{2}OH$).
• Hydrolysis to Phenol: Warming with water ($H_{2}O/{100}^{\circ }\text{C}$).
• Azo Coupling Reaction (Electrophilic Aromatic Substitution):
  • With Phenol at alkaline $\text{pH }9-10⟹$ $p$-Hydroxyazobenzene (Brilliant Orange Dye).
  • With Aniline at mildly acidic $\text{pH }4-5⟹$ $p$-Aminoazobenzene (Yellow Dye).