In-Depth Notes on Nucleophilic Substitution Reactions and Stereochemistry

Nucleophiles and Electrophiles

• Nucleophiles:
  • Definition: Electron-rich reagents that donate an electron pair to electron-poor sites.
  • Examples: -OH, :NH₃
• Electrophiles:
  • Definition: Electron-deficient reagents that accept an electron pair from nucleophiles.
  • Example: H⁺

Mechanisms in Organic Chemistry

• Organic Reaction Mechanism: Represents a complete, step-by-step account of how organic compound reactions occur.
  • Correlates initial reactants' structures and final product structures.
  • Accounts for changes in structure and energy, intermediate formation, and species interconversion rates.
• Curly Arrows: Used to illustrate and predict outcomes in reactions.
  • Indicate electron flow from high to low electron density.

Curly Arrows - Rule Overview

• Arrows represent electron pair movement.
  • Three Actions:
  1. Unshared pairs become shared.
  2. Shared pairs shift to adjacent bonding locations.
  3. Shared pairs become unshared.
• Drawing Rules:
  1. Arrow tail against the electron pair to be moved.
  2. Arrow head points to new location (atom or bond).

Substitution Reactions

• Characterized by breaking and forming new bonds at carbon.
• Involves:
  • Electron-Rich Nucleophile
  • Electron-Poor Electrophile
• Key question: Where are the electrons in starting materials?

Faster Substitution with Different Substrates

• Primary Substrates: Fast reactions expected.
• Tertiary Substrates: Can be faster than primary in some cases due to stability.

Stereochemistry in Substitution Reactions

• Some reactions lead to complete inversion of stereochemistry.
  • Example: SN₂ reactions cause inversion.
  • Others mix retention and inversion.

SN2 vs. SN1 Mechanisms

• SN2 Reaction:
  • Involves inversion of configuration at chiral centers.
  • Rate Law: Rate = k[R-Br][Nu], sensitive to both nucleophile and substrate.
  • Mechanism includes a single step, known as 'backside attack'.
• SN1 Reaction:
  • Kinetics are unimolecular: r = k[R-X]; rate only depends on electrophile.
  • Rate-limiting step involves a carbocation intermediate.
  • Fast nucleophilic attack follows.

Factors Influencing SN1 and SN2

• For SN1:
  • Stabilization of carbocations (3° > 2° > 1°) increases speed.
• For SN2:
  • Steric hindrance affects nucleophile approach; bulky groups hinder attacks.
• Leaving Groups: Stronger leaving groups make displacement easier.

Chirality and Biological Implications

• Chirality is crucial, as many biomolecules exist predominantly as single enantiomers.
  • Enantiomers formed during SN reactions can impact biological activity.
• Cahn-Ingold-Prelog Rules: Used for naming but less common in biological contexts.
• SN2 Inversion: Produces a single stereoisomer; SN1 may produce racemic mixtures due to a planar carbocation.