E2 reactions are a key type of elimination reaction in organic chemistry. They involve a base removing a proton while a leaving group departs, all in one step. This concerted mechanism creates a new carbon-carbon double bond.

Understanding E2 reactions is crucial for predicting organic reaction outcomes. The stereochemistry, substrate structure, and reaction conditions all play important roles in determining the products formed during these eliminations.

The E2 Reaction Mechanism

E2 reaction mechanism fundamentals

• Bimolecular elimination reaction occurs in a single concerted step
  • Simultaneous removal of a proton and departure of a leaving group from a substrate molecule
  • Base abstracts a proton from the $\beta$-carbon while the leaving group departs from the $\alpha$-carbon
• Rate depends on the concentrations of both the substrate and the base
  • Rate law: Rate = $k$[substrate][base]
  • Second-order overall, first-order in substrate and first-order in base
• Transition state involves partial bonding between the base and the $\beta$-hydrogen, and partial breaking of the C-H and C-LG bonds
  • Planar geometry with the $\beta$-hydrogen, $\alpha$-carbon, and leaving group all in the same plane
• Factors affecting the rate include:
  • Strength of the base: Stronger bases increase the reaction rate (NaOH)
  • Stability of the alkene product: More stable alkenes form faster (2-butene)
  • Steric hindrance: Bulky substituents near the reaction site slow down the reaction (tert-butyl group)

Key components of the E2 reaction

• Elimination reaction: The E2 reaction is a type of elimination reaction where two molecules are involved in the rate-determining step
• Leaving group: The group that departs from the α-carbon during the reaction, typically a halide or tosylate
• Beta hydrogen: The hydrogen atom on the carbon adjacent to the carbon bearing the leaving group, which is removed by the base
• Concerted mechanism: The E2 reaction occurs in a single step, with simultaneous breaking and forming of bonds

Evidence for the E2 Mechanism

Deuterium isotope effect evidence

• Investigates the rate-determining step of the E2 reaction
  • Deuterium (D) is an isotope of hydrogen with one proton and one neutron in its nucleus
  • C-D bond is stronger than the C-H bond due to the higher mass of deuterium
• Substrate containing a $\beta$-deuterium undergoes an E2 reaction slower compared to the same substrate with a $\beta$-hydrogen
  • Breaking the C-D bond requires more energy than breaking the C-H bond
  • Observed rate difference is called the kinetic isotope effect (KIE)
• Significant KIE suggests cleavage of the C-H/C-D bond is involved in the rate-determining step
  • Supports the concerted, one-step mechanism of the E2 reaction where the base abstracts the $\beta$-hydrogen in the same step as the leaving group departs
• Magnitude of the KIE for the E2 reaction is typically between 2 and 7
  • Larger KIE indicates a greater involvement of the C-H/C-D bond breaking in the rate-determining step

Stereochemistry of E2 Eliminations

Stereochemistry of E2 eliminations

• Determined by the periplanar geometry of the transition state
  • Periplanar geometry requires the $\beta$-hydrogen, $\alpha$-carbon, and leaving group to lie in the same plane
  • Arrangement allows for optimal orbital overlap and minimizes the energy of the transition state
• Periplanar requirement leads to anti-elimination
  • $\beta$-hydrogen and leaving group must be anti-periplanar (on opposite sides) relative to the C-C bond
  • Elimination occurs more readily when the leaving group is anti to the $\beta$-hydrogen
• In cyclic systems, the leaving group must be axial for the E2 reaction to occur
  • Axial leaving group allows for the necessary anti-periplanar arrangement with the $\beta$-hydrogen
  • Equatorial leaving groups cannot achieve the required periplanar geometry, making elimination difficult (cyclohexyl bromide)
• Stereochemistry of the resulting alkene depends on the stereochemistry of the substrate
  • Anti-elimination of a syn-disubstituted substrate leads to the (E)-alkene (trans-2-butene)
  • Anti-elimination of an anti-disubstituted substrate leads to the (Z)-alkene (cis-2-butene)
• In cases where multiple $\beta$-hydrogens are present, the more substituted or more stable alkene will be formed preferentially (Zaitsev's rule)
  • Due to the greater stability of the more substituted alkene and the lower energy of its transition state (2-pentene vs 1-pentene)