Overview
Lecture covers E2 elimination reactions focusing on regioselectivity, explaining how base size determines whether Zaitsev or Hofmann products predominate in elimination reactions of alkyl halides.
E2 Elimination Basics
- E2 reactions involve strong bases removing beta protons from alkyl halides
- Alpha carbon is bonded to the leaving group (halide)
- Beta carbons are adjacent to alpha carbon and contain removable protons
- Multiple beta carbons can lead to different elimination products
- Product distribution depends on which beta proton is removed
Regioselectivity Rules
- Zaitsev product: more highly substituted alkene, thermodynamically more stable
- Hofmann product: less substituted alkene, sterically less hindered
- Non-bulky bases favor Zaitsev product formation
- Bulky, sterically hindered bases favor Hofmann product formation
- Base selection allows control over reaction regioselectivity
Base Selection and Product Distribution
| Base Type | Example | Major Product | % Zaitsev | % Hofmann |
|---|
| Non-bulky | Sodium ethoxide | Zaitsev | High | Low |
| Moderately bulky | tert-Butoxide | Hofmann | Lower | Higher |
| Highly hindered | Sterically hindered base | Hofmann | Lowest | Highest |
Common Non-Nucleophilic Bases
- Potassium tert-butoxide (KOtBu): moderately bulky, favors Hofmann products
- Diisopropylamine: bulky structure limits access to more substituted positions
- Triethylammonium: nitrogen surrounded by three ethyl groups
- Steric hindrance prevents these bases from functioning as nucleophiles
- Lone pairs function exclusively as bases rather than nucleophiles
Predicting Products
- Identify alpha carbon (bonded to leaving group)
- Locate all beta carbons with removable protons
- Evaluate base size and steric hindrance
- Non-bulky base: expect Zaitsev as major, Hofmann as minor
- Bulky base: expect Hofmann as major, Zaitsev as minor
- Beta carbons without protons cannot participate in elimination
Key Terms & Definitions
- Alpha carbon: carbon directly bonded to leaving group
- Beta carbon: carbon adjacent to alpha carbon
- Beta proton: hydrogen on beta carbon, removable by base
- Zaitsev product: more substituted alkene from elimination
- Hofmann product: less substituted alkene from elimination
- Regioselectivity: preference for reaction at specific molecular region
- Sterically hindered base: bulky base with limited access to crowded areas