Lecture Notes: Organic Chemistry - Ethers and Epoxides

Announcements

• Quizzes:
  • Quizzes for Quiz 4 are available.
  • Quiz 5 will be posted soon and is due on Wednesday at midnight.
    • Answers will be released at midnight (12:01 AM Thursday) with no late submissions allowed.
    • Quiz 5 includes career-relevant questions in addition to content.
• Upcoming Exam:
  • Next Friday.
  • Monday and Wednesday will be dedicated to review.
  • One topic related to Grignard reactions will be revisited before the exam.
• Resources:
  • SI leaders and TAs are available for guidance.

Review: Quiz 3 Issues

• Question #7 had a typo, leading to everyone receiving full credit.
• Synthesis Question:
  • Follow the rules given in questions, such as using hydrocarbons and specific reaction conditions.
  • Ozonolysis should be recognized as a key reaction for synthesis problems.
• Additional practice available in Chapter 17 and 18 workbooks.

Ethers and Epoxides

Williamson Ether Synthesis

• Involves deprotonating an alcohol using sodium hydride, followed by an SN2 reaction with a primary alkyl halide.
• Mechanism:
  1. Alcohol reacts with sodium hydride to form alkoxide ion.
  2. Alkoxide acts as a nucleophile in an SN2 reaction with an alkyl halide.
• Important:
  • Alkyl halide must be primary to avoid elimination reactions.

Epoxides

• Structure: Three-membered cyclic ethers.
• Highly electrophilic due to ring strain and oxygen’s electronegativity.
• Reactions with nucleophiles:
  • Strong nucleophiles add to the less substituted carbon.
  • Weak nucleophiles, with an acid catalyst, add to the more substituted carbon.
• Example Reactions:
  • Using hydroxide as a nucleophile results in anti-Markovnikov opening.
  • Grignard reagents can add to epoxides to form alcohols with new carbon-carbon bonds.

Key Concepts

• Sterics and Regiochemistry:
  • Strong nucleophiles favor less substituted carbon.
  • Weak nucleophiles (neutral) favor more substituted carbon with acid catalyst.
• Stereochemistry:
  • SN2-like mechanism leads to inversion of configuration at the carbon where nucleophile adds.
• Applications in Synthesis:
  • Different outcomes for alcohol placement when reacting aldehydes/ketones vs epoxides with Grignard reagents.

Upcoming

• Further discussion of epoxide reactions and mechanisms on Monday.
• Prepare for practice problems and review sessions next week.