Reactions Associated with Amines

SN2 Reaction with Ammonia

• Example: Reaction of 1-bromobutane with excess ammonia.
• Mechanism:
  • Ammonia acts as a nucleophile, attacks carbon, expels leaving group (bromide).
  • Nitrogen ends up with a positive charge due to four bonds.
  • Another NH3 removes a hydrogen, yielding butylamine.

Exhaustive Methylation

• Problem: Ammonia with methyl bromide can lead to over-alkylation.
• Process:
  • Stepwise addition of methyl groups to nitrogen, forming methyl amine, dimethylamine, etc., up to a quaternary ammonium ion.

Synthesis of Amines

Sodium Azide Method

• Reactant: Alkyl halide with sodium azide (NaN3).
• Mechanism:
  • Azide ion acts as nucleophile in SN2 reaction, displaces halide.
  • Reduction with lithium aluminum hydride (LiAlH4) and H2O removes excess nitrogen, forming an amine.

Cyanide Ion Method

• Reactant: Alkyl halide with sodium cyanide (NaCN).
• Mechanism:
  • Cyanide ion as nucleophile forms a nitrile.
  • Reduction (using H2/Nickel or LiAlH4) converts nitrile to amine.

Gabriel Synthesis

• Reactant: Thalimide with potassium hydroxide and alkyl halide.
• Mechanism:
  • Deprotonation and nucleophilic attack forms alkylated thalimide.
  • Reaction with hydrazine yields primary amine and thalimide hydroxide.

Reduction of Nitro Groups

• Process: Nitro group (NO2) reduced to NH2.
• Methods:
  • Iron and hydrochloric acid.
  • Catalytic hydrogenation with metal catalyst.

Reductive Amination

• Reactants: Ketones or aldehydes with ammonia or primary amines.
• Mechanism:
  • Formation of imine, reduced to amine using sodium cyanoborohydride.
  • Yields primary, secondary, or tertiary amines based on initial reactants.

Acylation Reduction

• Reactants: Acyl chloride with ammonia or amines.
• Mechanism:
  • Reaction forms amide.
  • Reduction with LiAlH4 converts amide to amine.

Rearrangement Reactions

Hofmann Rearrangement

• Reactants: Amide with halogen under basic conditions.
• Outcome: Loss of carbonyl group, formation of amine with one less carbon.

Curtius Rearrangement

• Reactants: Acyl chloride with sodium azide.
• Outcome: Formation of isocyanate intermediate, conversion to amine with loss of carbon.

Elimination Reactions

Hofmann Elimination

• Process: Converts amine to alkene.
• Steps:
  • Exhaustive methylation using methyl iodide.
  • Followed by reaction with silver oxide and water, forming a better leaving group.
  • Elimination gives less stable alkene (Hofmann product).

Cope Elimination

• Reactants: Tertiary amine oxidized to amine oxide.
• Mechanism:
  • Syn elimination forms less substituted alkene due to cyclic transition state.

Reaction of Amines with Carbonyls

• With Ketones/Aldehydes: Forms imines, reducible to amines.
• Ammonia with Unsaturated Ketones: Attacks beta carbon, favoring conjugate addition over direct addition.

Conclusion

• Discussed various reactions to synthesize and transform amines, including methylation, reductive amination, rearrangements, and eliminations.