SN1, SN2, E1, and E2 Reactions Lecture Notes

Introduction

• Overview of reaction mechanisms: SN1, SN2, E1, and E2.
• Importance of substrate type, solvent, and base strength in determining reaction pathway.

SN2 Reactions

• Methyl Substrate (e.g., Methyl Bromide): Proceeds via SN2 regardless of solvent or base.
• Primary Substrate (e.g., Ethyl Bromide):
  • SN2 is favored unless a bulky base is used, which leads to E2.
  • Strong, unhindered base (e.g., hydroxide) typically results in SN2.
  • Sterically hindered bases favor E2 over SN2.

E2 Reactions

• Occur with bulky bases and/or sterically hindered substrates.
• Secondary Alkyl Halide with Strong Base: E2 is often the major product.

SN1 and E1 Reactions

• Secondary Alkyl Halide with Protic Solvent:
  • Protic solvents favor SN1/E1 but can sometimes lead to SN2.
• Tertiary Alkyl Halide:
  • Leads to SN1 and E1; SN2 does not occur due to steric hindrance.
  • Protic solvents favor SN1; heat favors E1 over SN1.

Reaction Mechanism Examples

Example 1: Two Bromo Butane with Sodium Cyanide in Acetone

• SN2 reaction due to secondary alkyl halide and good nucleophile.
• Backside attack results in inversion of configuration.

Example 2: Tert-butyl Chloride with Water

• Tertiary substrate in protic solvent leads to SN1 and E1.
• SN1 results in substitution with OH group.
• E1 results in elimination to form a double bond (alkene).

Example 3: Reaction of Tertiary Alkyl Halide with Methanol

• Solvolysis reaction (SN1/E1 mechanism).
• SN1 leads to ethers with a racemic mixture of stereoisomers.
• E1 yields alkenes.

Mechanistic Insights

• SN2 Mechanism: Inversion of configuration due to backside attack.
• E1 Mechanism: Transition states and stability influence product.
• Influence of Leaving Groups: Better leaving groups favor SN1 and more stable transition states.

Factors Affecting Reaction Pathways

• Steric Hindrance: Affects SN2; bulky groups favor elimination (E2).
• Solvent: Protic solvents favor substitutions/eliminations; aprotic solvents favor substitutions.
• Base Strength and Nucleophile: Strong bases and good nucleophiles can push reactions towards E2 or SN2.

Special Cases and Exceptions

• Sterically hindered primary substrates can lead to SN1 or E1 due to carbocation rearrangements.
• Bad leaving groups (e.g., fluoride) can alter E2 to favor Hoffman product.

Comparative Analysis

• Comparison of reactions with different bases, solvents, and leaving groups for deeper understanding of mechanisms.

Summary

• Guidelines for predicting reaction pathways:
  • Methyl substrates: SN2
  • Primary: SN2 or E2 (with bulky base)
  • Secondary: Complicated; consider solvent, base, sterics
  • Tertiary: SN1/E1 except with strong base (E2)
• Importance of considering all factors for accurate prediction.