Chapter 14: Ethers and Epoxides

Students then review the Williamson Ether Synthesis, a two-step SN2 process for creating ethers from alcohols and alkyl halides, with key restrictions on electrophile structure (must be primary or methyl). The chapter explains acidic cleavage of ethers using HX, differentiating between SN1 and SN2 pathways depending on whether the alkyl group is primary or tertiary. It then shifts focus to epoxides, three-membered cyclic ethers that form via peroxyacid oxidation of alkenes (e.g., with MCPBA) in a stereospecific manner. Students learn that cis alkenes give meso epoxides, while trans alkenes give racemic mixtures. Epoxides undergo ring-opening reactions, and the regiochemical and stereochemical outcome depends on the reaction conditions: under basic conditions, nucleophiles attack the less-substituted carbon via SN2 with inversion, while under acidic conditions, they attack the more-substituted carbon due to carbocationic character. The chapter concludes with extensive examples using strong nucleophiles (like NaCN, LiAlH₄, or Grignard reagents) and weak nucleophiles in acidic solvents (like methanol or water), reinforcing mastery of both mechanism and product prediction.