Synthesis of Amines

Overview

• Topic: Synthesis of amines in organic chemistry
• Presentation includes a review of previous reactions and introduction to new syntheses
• Key syntheses discussed:
  • Hoffman rearrangement
  • Curtius rearrangement
  • Schmidt reaction
  • Gabriel synthesis
  • Reductive amination

Reactions Overview

1. Reduction Reactions

• Reduction of Nitro Compounds
  • Convert nitro group to amine group
  • Methods: Catalytic hydrogenation or active metals (Zn, Sn, Fe) with acid
  • Example: Nitrobenzene to Aniline
• Reduction of Nitriles
  • Convert C≡N to C-N with lithium aluminum hydride (LiAlH₄)
• Reduction of Azides
  • New reaction
  • Similar mechanism, azide reduced to amine, using LiAlH₄ or catalytic hydrogenation
• Reduction of Amides
  • Use LiAlH₄ and H3O+
  • Lose oxygen, add two hydrogens

2. Hoffman Rearrangement

• Converts amides to amines with one fewer carbon
• Mechanism involves nucleophilic attack, rearrangement, isocyanate intermediate
• Hydrolysis of isocyanate leads to amine and CO2
• Key: Different from amide reduction in product carbon count

3. Curtius Rearrangement

• Similar to Hoffman, but starts with carboxylic acids
• Converts to isocyanate intermediate
• Ends with amine and loss of CO2

4. Schmidt Reaction

• Similar to Curtius
• Starts with carboxylic acid, uses azides
• Ends with formation of amine and CO2

5. Gabriel Synthesis

• Used for synthesis of primary amines
• Starts with phthalimide
• Involves alkylation followed by hydrolysis
• Avoids over-alkylation problem of direct amine alkylation

6. Reductive Amination

• Forms amines one substitution degree higher
• Involves reaction with aldehydes/ketones forming imines or enamines
• Reduction step typically uses sodium cyanoborohydride
• Converts ammonia to primary amine, primary to secondary, secondary to tertiary

Practical Applications

• Each synthesis method has specific applications and advantages
• Suitable choice depends on desired amine type and starting materials

Conclusion

• Lesson part of organic chemistry series
• Emphasis on understanding mechanisms and outcomes
• Encouragement to engage with more organic chemistry resources for deeper learning