SN2 Reaction Mechanism Lecture Notes

Introduction to SN2 Reaction

• SN2 Reaction: Stands for "Substitution Nucleophilic Bimolecular".
• Key Players:
  • Nucleophile: Hydroxide ion (OH⁻) with a negative charge.
  • Substrate: Alkyl halide.
  • Leaving Group: Usually a halide like bromide.
  • Example Reaction: Hydroxide ion attacks methyl group, expels bromine, forming methanol.
  • Transition State: Partial bonds between carbon, nucleophile (oxygen), and leaving group (bromine).

Reaction Mechanism

• Nucleophilic Attack: Nucleophile approaches from the back, avoids repulsion from bromine's partial negative charge.
• Product Formation: Methanol and bromide ion.
• Second Order Reaction: Rate depends on both nucleophile and substrate concentrations.

Factors Affecting SN2 Reactions

Solvent Effects

• Polar Aprotic Solvents: Enhance SN2 reactions, no OH or NH bonds (e.g., acetone, DMSO).

Reactivity of Alkyl Halides

• Order of Reactivity: Primary > Secondary > Tertiary.
• Steric Hindrance: Bulkier groups reduce reactivity.
• Example: Tertiary alkyl halides are too hindered for SN2, react slowly.

Nucleophile Strength

• Strong Nucleophiles: Anions like OH⁻, methoxide.
• Comparison: Hydroxide is stronger nucleophile than water.
• Periodic Trends:
  • In protic solvents: Iodide > Bromide > Chloride > Fluoride.
  • In aprotic solvents: Fluoride > Chloride > Bromide > Iodide.

SN2 Reaction Examples

Example 1

• Reaction: Butyl bromide with sodium methoxide.
• Product: Ether formation.

Example 2

• Reaction: 2-Bromo-butane with potassium iodide in acetone.
• Product: Inversion of configuration at chiral center (R to S).

Example 3

• Reaction: 1-Bromo-3,3-methyl-cyclohexane with sodium cyanide in DMSO.
• Product: Cyanide in equatorial position, inversion from axial bromine.

Energy and Reaction Diagram

• Single Transition State.
• Activation Energy: Difference between reactants and transition state.

Comparison of Alkyl Halides

• Most Reactive: Primary alkyl halides.
• Least Reactive: Tertiary alkyl halides.
• Special Cases: Aryl and vinyl halides are less reactive due to pi electron interference.

Practical Tips

• Nucleophilic Substitution Preference: Favor less sterically hindered substrates.
• Choose Solvent Wisely: Aprotic solvents for SN2, protic for SN1.

Example Problem

• Reactants: 1-Bromobutane with hydroxide vs. water.
• Conclusion: Hydroxide reaction proceeds faster due to stronger nucleophile.

Summary

• SN2 Mechanism: Concerted, single-step reaction with simultaneous bond-forming and bond-breaking.
• Nucleophile and Substrate Concentrations: Crucial for reaction rate, overall second-order kinetics.