Synthesis of Thiazole

Synthesis of Thiazole explains key routes like Hantzsch, Gabriel, and cyclization strategies with reagents, mechanisms, and applications.

1. Hantzsch Thiazole Synthesis (Classical and widely used)

   • Reactants: α-haloketone + thioamide
   • Conditions: Reflux in ethanol or basic medium
   • Reaction:
     • CH₃COCH₂Cl + NH₂–CS–NH₂ → Thiazole derivative
   • Mechanism:
     • Nucleophilic attack by thioamide
     • Cyclization
     • Elimination of HCl

2. Gabriel Synthesis

   • Uses α-haloketone and thiourea
   • Reaction:
     • CH₃COCH₂Br + NH₂–CS–NH₂ → 2-Aminothiazole

3. Gewald Reaction (For 2-amino-thiazoles)

   • Reactants: α-cyanoester + sulfur + ketone
   • Conditions: Basic (e.g., piperidine)
   • Reaction:
     • CH₃COCH₃ + S + NCCH₂COOEt → 2-Aminothiazole derivative
   • Useful in pharmaceutical synthesis

4. From Dithioformic acid and α-haloketones

   • Produces various substituted thiazoles

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