Analyzing Organic Reactions: Nucleophiles, Electrophiles, and Leaving Groups

Introduction

Reactions in organic chemistry can be divided into two groups:
- Oxidation-reduction reactions
- Nucleophile-electrophile reactions
Focus for Objective 2: Define nucleophiles, electrophiles, and leaving groups, and discuss nucleophilic substitution reactions (SN2).

Definition: Nucleus-loving species with lone pairs or π bonds that can form new bonds to electrophiles.
Differences from Bases:
- Nucleophile strength: Kinetic property (reaction rates with electrophiles)
- Base strength: Thermodynamic property (equilibrium position of a reaction)
Examples of Nucleophiles:
- Anions (e.g., Br-, OH-, CN-)
- Molecules with π bonds (e.g., C=C, C≡C, benzene rings)
- Atoms with lone pairs (e.g., H2O, NH3)
Factors Determining Nucleophilicity:
- Charge: Increases with increasing electron density
- Electronegativity: Decreases with increasing electronegativity
- Steric Hindrance: Bulkier molecules are less nucleophilic
- Solvents: Protic solvents can hinder nucleophilicity

Polar Protic Solvents: Nucleophilicity increases down the periodic table
Polar Aprotic Solvents: Nucleophilicity increases up the periodic table
Example with Halogens:
- Protic solvents: I- > Br- > Cl- > F-
- Aprotic solvents: F- > Cl- > Br- > I-
Non-Polar Solvents: Not used because nucleophiles need to dissolve

Definition: Electron-loving species with a positive charge or polarized atom that accepts an electron pair forming bonds
Differences from Acids:
- Electrophilicity: Kinetic property
- Acidity: Thermodynamic property
Examples:
- Carbo cations (very electrophilic)
- Carbonyl carbons (less electrophilic)
Factors Affecting Electrophilicity:
- Positive Charge: Greater degree increases electrophilicity
- Nature of Leaving Group: Better leaving groups enhance reaction likelihood

Definition: Molecular fragments that retain electrons post-heterolysis
Properties of Good Leaving Groups:
- Ability to stabilize extra electrons
- Weak bases make better leaving groups (e.g., conjugate bases of strong acids: I-, Br-, Cl-)
Examples of Poor Leaving Groups:
- Alkyl and hydrogen ions (form reactive anions)

SN2 Reactions: Overview
- One-step (concerted) mechanism
- Bimolecular reaction (rate dependent on nucleophile and substrate concentration)
- Example: A nucleophile attacks an electrophilic carbon attached to a leaving group
- Energy Diagram: Shows one transition state (no intermediates)

Backside Attack: Nucleophile displaces leaving group
Factors Influencing SN2 Reactions:
- Less substituted carbons are more reactive
- Inversion of configuration at chiral centers