Reactions with Ethers and Epoxides

Ether Synthesis

Williamson Ether Synthesis

• Steps:
  1. Use a strong base (e.g., Sodium hydride, NaH) to form an alkoxide ion and hydrogen gas.
  2. React the alkoxide ion with an alkyl halide (e.g., ethyl bromide) in an SN2 reaction to form an ether.
• Key Points:
  • Use methyl and primary halides to avoid E2 reactions.
  • Example: Phenol + Sodium Hydroxide (NaOH) + Methyl Bromide → Methyl Phenyl Ether.
  • Phenol is more acidic (pKa = 10) than typical alcohols (pKa = 16-18) hence NaOH works effectively.

Reactions with Tert-Butoxide

• Behavior: Acts as a base due to steric hindrance, prefers to abstract hydrogen over nucleophilic attacks.
• Outcome: Formation of a six-membered ether ring through intramolecular reactions.

Ether Formation from Alkenes

Acidic Conditions with Methanol

• Mechanism:
  1. Hydrogen from acid adds to alkene leading to a more stable carbocation.
  2. Methanol attacks carbocation, forming a species.
  3. Further reaction with methanol leads to ether formation.

Alkoxymercuration-Demercuration

• Reagents: Mercury acetate, ethanol, followed by sodium borohydride.
• Result: Ether added to a secondary carbon.

Acid-Catalyzed Cleavage of Ethers

Reaction with Hydroiodic Acid (HI)

• Mechanism:
  • Tertiary carbocation intermediate formed after protonation and leaving of oxygen.
  • Iodide ion attacks to form alkyl halide.
• Products:
  • 1 equivalent HI: Produces tert-butyl iodide and methanol.
  • Excess HI: Converts methanol to methyl iodide, no alcohol remains.

Important Considerations

• Phenol: Cannot convert to a phenyl iodide using HI.
• General Alcohols: Excess HI converts all to alkyl halides.