Synthesis of Pyridine

Synthesis of Pyridine covers Hantzsch, Kröhnke, and Bohlmann–Rahtz routes with reagents, mechanisms, and medicinal chemistry applications.

1. Hantzsch Pyridine Synthesis (most common lab method)

   • Reactants: Aldehyde + β-keto ester + ammonia
   • Conditions: Reflux in ethanol
   • Example:
     • 2 CH₃COCH₂COOEt  +  CH₃CHO  +  NH₃  →  Dihydropyridine  →  Pyridine (oxidation)
     • The dihydropyridine intermediate is oxidized (e.g., with nitric acid or air) to form pyridine.

2. Chichibabin Synthesis

   • Reactants: Aldehyde + formaldehyde + ammonia
   • Example: Acetaldehyde + formaldehyde + NH₃ → Pyridine derivative

3. Industrial Synthesis

   • Reactants: Acetaldehyde + formaldehyde + ammonia
   • Conditions: Vapor phase, 350–500 °C, aluminum oxide catalyst
   • Example:
     • CH₃CHO  +  HCHO  +  NH₃  →  Pyridine  +  H₂O

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