Reactions of Quinoline

Reactions of Quinoline involve electrophilic substitution, nucleophilic substitution, oxidation, and reduction crucial in drug development.

Reactions of Quinoline

1. Electrophilic Substitution (EAS)

   • Preferred Sites:
     • C-5 and C-8 on the benzene ring (electron-rich)
     • C-3 and C-4 are deactivated
   • Typical Reactions:
     • Nitration (mild): C-5 or C-8
     • Sulfonation: C-5 or C-8
     • Halogenation: Br₂ or Cl₂ at benzene ring positions

2. Nucleophilic Substitution (NAS)

   • More reactive at C-2 and C-4 (near nitrogen)
   • Substitution occurs if good leaving group and EWG present
   • Example:
     • 2-chloroquinoline + NH₃ → 2-aminoquinoline

3. Reduction Reactions

   • Catalytic hydrogenation:
     • Whole ring: → tetrahydroquinoline or decahydroquinoline
     • Selective: e.g., only pyridine ring reduced under mild conditions.
   • Birch reduction:
     • Li/NH₃ → partial reduction at benzene ring

4. Oxidation

   • Oxidation with KMnO₄:
   • Alkyl groups → carboxylic acid
   • Ring oxidation under harsh conditions possible

5. Metal Coordination

   • Quinoline coordinates via nitrogen to form metal complexes
   • Used in photochemistry, catalysis, and drug design

6. Synthesis and Functionalization

   • Skraup synthesis: Classic method of quinoline preparation using aniline + glycerol + oxidant (e.g., nitrobenzene).

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