Chapter 14: Ethers, Epoxides, and Thioethers

Ethers

• Formula: ROR where R is an alkyl or aryl group.
• Types: Symmetrical or unsymmetrical.
• Structure and Polarity:
  • Oxygen is sp3 hybridized with a bent molecular geometry.
  • Tetrahedral C-O-C bond angle is approximately 110 degrees.
  • Bonds are polar.
• Boiling Points: Comparable to alkanes of similar molecular weight.
• Hydrogen Bonding:
  • Cannot hydrogen bond with other ether molecules, resulting in lower boiling points than alcohols.
  • Can hydrogen bond with water and alcohols, acting as hydrogen bond acceptors.

Ethers as Solvents

• Dissolve both polar and nonpolar substances.
• Unreactive towards strong bases, low boiling points simplify evaporation.
• Solvation of Ions:
  • Ionic substances like lithium iodide are soluble due to solvation by ether's lone pairs.
  • Ethers cannot serve as hydrogen bond donors.

Ether Complexes

• Grignard Reagents: Ethers stabilize and keep Grignard reagents in solution.
• Electrophiles: Nonbonding electrons stabilize borane.
• Crown Ether Complexes:
  • Complex metal cations based on ring size.
  • Enable dissolution of polar inorganic salts in nonpolar solvents.

Naming Ethers

• Common Names: Name alkyl groups attached to oxygen, followed by 'ether'.
• IUPAC Names: More complex alkyl group is the parent name, smaller becomes an alkoxy group.

Williamson Ether Synthesis

• Involves SN2 attack of alkoxide on primary halide/tosylate.
• Alkoxide made by adding Na, K, or NaH to alcohol.

Phenyl Ethers

• Phenoxide ions formed easily due to phenols being more acidic than aliphatic alcohols.
• Phenol used as alkoxide fragment in synthesis, not halide.

Ether Cleavage

• Cleaved by heating with concentrated HBr/HI.
• Protonated ether undergoes substitution via SN1 or SN2 depending on substituents.
• Phenyl ethers do not react further to halides.

Autoxidation of Ethers

• Ethers oxidize to hydroperoxides and dialkyl peroxides; both are explosive.
• Store in full bottles with tight caps to mitigate risk.

Protecting Groups

• Silyl Ethers: Protect alcohols from unwanted reactions.
  • Resistant to some acids, bases, and oxidizing agents.
  • Can be hydrolyzed easily.

Cyclic Ethers (Heterocycles)

• Include epoxides, oxetanes, furans (THF), pyrans (THP), and dioxanes.

Epoxides

• Nomenclature: Named by starting alkene + 'oxide'.
• Synthesis:
  • Peroxyacid Epoxidation: Converts alkenes to epoxides using peroxyacids like MCPBA.
  • Selectivity: Electron-rich bonds react faster; maintains stereochemistry.
  • Halohydrin Cyclization: Forms rings through an internal SN2 attack.
• Opening Reactions:
  • Protonation followed by nucleophilic attack opens the ring.
  • Regioselectivity: Nucleophile adds to more substituted carbon in acid-catalyzed conditions.

Reaction with Grignard and Organolithiums

• Strong bases open epoxide rings attacking less hindered carbon.

Biosynthesis of Steroids

• Squalene epoxidation leads to steroid biosynthesis.

Thioethers

• Structure: RSR, analogous to ether.
• Synthesis: Via Williamson ether synthesis using thiolate ion.
• Reactions:
  • Oxidized to sulfoxides and sulfones.
  • React with alkyl halides to form sulfonium salts.
  • Used as mild reducing agents due to easy oxidation.