Lecture on Nucleophilic Substitution Reactions

Overview

• Focus on two common types of nucleophilic substitution reactions:
  • SN1 Reaction
  • SN2 Reaction

SN2 Reaction

• Second-order reaction: rate depends on concentration of substrate and nucleophile.
• Rate:
  • First-order with respect to both substrate and nucleophile.
  • Overall rate is second-order (1 + 1 = 2).
  • Doubling concentration of either doubles the reaction rate.
  • Example: Doubling substrate and tripling nucleophile increases rate by factor of 6.
• Substrate: Typically an alkyl halide (e.g., 2-bromo-butane).
• Mechanism:
  • Single-step, concerted mechanism.
  • Involves inversion of stereochemistry due to back-side attack by nucleophile.
  • No carbocations; no rearrangements.
• Preference:
  • Best with methyl substrates, then primary.
  • Ineffective with tertiary substrates due to steric hindrance.
• Example:
  • Methyl bromide reacts well with hydroxide (SN2), but tert-butyl bromide does not.

SN1 Reaction

• First-order reaction: rate depends only on concentration of the substrate.
• Steps:
  • Formation of a carbocation (rate-limiting step).
  • Nucleophile attack (fast step).
• Mechanism:
  • Two-step process with negatively charged nucleophile.
  • Three-step process with neutral nucleophile (solvolysis).
  • Carbocation can lead to rearrangements.
  • Results in racemic mixtures when nucleophile attacks from front and back.
• Preference:
  • Works better with tertiary substrates due to stable carbocation formation.
  • Methyl substrates ineffective due to instability.
• Example:
  • Tert-butyl bromide forms stable tertiary carbocation, reacts with iodide.

Additional Considerations

• Protic vs Aprotic Solvents:
  • Protic solvents favor SN1 reactions.
  • Polar aprotic solvents favor SN2 reactions.
• Example Mechanisms:
  • Secondary carbocation can rearrange through hydride or methyl shifts.
  • Reaction with methanol forms ether, reaction with water forms alcohol.
  • Chiral centers in products lead to stereoisomers.

Practice and Resources

• Mention of additional resources such as practice tests and other tutorial videos for further learning on nucleophilic substitution reactions.