Synthesis of Quinoline

Synthesis of Quinoline covers Skraup, Doebner–Miller, Friedländer, and Combes routes with key reagents, mechanisms, and uses.

1. Skraup Synthesis (classical method)

   • Reactants: Aniline + glycerol + oxidizing acid (e.g., H₂SO₄ + nitrobenzene)
   • Mechanism: Glycerol is dehydrated to acrolein, which condenses with aniline, followed by cyclization and oxidation.
   • Reaction:
     • Aniline  + Glycerol  +  H₂SO₄  +  Nitrobenzene  →  Quinoline

2. Doebner–Von Miller Synthesis

   • Reactants: Aniline + aldehyde + pyruvic acid
   • Conditions: Acidic reflux
   • Reaction:
     • Aniline  +  CHO–R  +  CH₃COCOOH  →  Substituted quinoline

3. Friedländer Synthesis

   • Reactants: 2-aminobenzaldehyde + carbonyl compound (ketone)
   • Conditions: Acid/base catalysis
   • Example:
     • • 2-Aminobenzaldehyde  +  Acetone  →  Quinoline derivative
     • Widely used for substituted quinolines in drug synthesis

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