Organic Chemistry Series: Name Reactions

Importance of Name Reactions

• Name reactions have synthetic utility and are typically named after their discoverers or developers.
• Useful shorthand in organic chemistry to refer to specific reactions.
• Important for exams and chemistry research.

Examples of Name Reactions

• Previously Covered:
  • Williamson ether synthesis
  • Robinson annulation
  • Claisen condensation
  • Friedel-Crafts reactions
  • Clemmensen reduction
  • Grignard reaction
  • Wittig reaction
  • Beckmann rearrangement
  • Baeyer-Villiger oxidation

Gabriel Synthesis

• Purpose: Method of generating primary amines.
• Problem Addressed: Difficulty in synthesizing primary amines without side reactions like elimination or multiple alkylations.
• Solution: Use of potassium salt of phthalimide and alkyl halides in dipolar solvents, following an SN2 mechanism.

Reaction Details

• Phthalimide: Acts as a protected version of ammonia, reducing basicity and avoiding multiple alkylations.
• Solvents: DMSO or DMF are typically used.
• Mechanism:
  • SN2 reaction between primary alkyl halide and phthalimide.
  • Negative charge in phthalimide is stabilized across two carbonyl groups, reducing basicity.

Hydrolysis

• Methods:
  • Highly acidic/basic conditions.
  • Milder conditions using hydrazine to form phthalyl hydrazide and primary amine.

Considerations

• Best suited for primary alkyl halides due to reactivity.
• Side Reactions: Possible formation of O-alkylation product due to phthalimide being an ambident nucleophile.
• Detection: Distinguishing between N-alkylation and O-alkylation products can be challenging.

Variations

• Modified Synthesis: Use of differentially protected ammonia surrogates.
• Example: Benzyl tert-butyl imidodicarbonate for secondary amines with two different alkyl groups.
• Process:
  • Palladium-catalyzed hydrogenolysis to remove benzyloxy carbonyl group.
  • Second alkylation and removal of tert-butoxycarbonyl group under mildly acidic conditions.

Conclusion

• Gabriel synthesis remains a classic and important reaction in organic synthesis.
• Understanding variations and original synthesis is crucial for modern synthetic applications.