Synthesis

• Hofmann degradation (aka Hofmann rearrangement) of amides to amines
  • Amides with an unsubstituted nitrogen can react with chlorine or bromine in a base to produce an amine:
    

    Figure 52.6: Hofmann degradation.

    

• Hofmann elimination
  • $E2$ elimination when a quaternary ammonium hydroxide is heated to produce an alkene, water and a tertiary amine:
    

    Figure 52.7: Hofmann elimination.

    

• Primary amine synthesis from reacting ammonia with alkyl halides (aka Gabriel synthesis)
  

  Figure 52.8: Primary amine synthesis: Gabriel synthesis.

  

• Reduction of nitro compounds
  

  Figure 52.9: Reduction of nitro compounds.

  

• Reductive animation of aldehydes or ketones.
  • Formation of 1$^{o}$, 2$^{o}$ and 3$^{o}$ amines
    

    Figure 52.10: Amine synthesis: Reductive animation of aldehydes or ketones to create primary, secondary or tertiary amines. For secondary and tertiary amines, a ketone needs to be used as the substrate reactant.

    

• Reduction of nitriles, oximes and amides
  • Formation of 1$^{o}$ and 3$^{o}$ amines
    

    Figure 52.11: Formation of 1$^{o}$ amines from the reduction of nitriles or oximes and the formation of 3$^{o}$ amines from the reduction of amides.