Substitution versus Elimination

Substitution vs. Elimination

Substitution and elimination reactions are two competing pathways in organic chemistry. Understanding the factors that influence which reaction occurs is crucial.

Review

  • Substitution: One atom or group is replaced by another.
    General Equation: R-LG + Nu → R-Nu + LG⁻
    Example: CH₃Br + OH⁻ → CH₃OH + Br⁻
  • Elimination: A double bond is formed by removing atoms or groups from adjacent carbons.
    General Equation: R-CH₂-CH₂-LG + Base → R-CH=CH₂ + LG⁻ + H-Base⁺
    Example: CH₃CH₂Br + OH⁻ → CH₂=CH₂ + Br⁻ + H₂O

Key Factors

  • Nucleophile (Nu): Electron-rich species seeking positive charge. Attacks electrophilic carbon in substitution.
  • Base: Species that accepts a proton (H⁺). Abstracts a proton in elimination.
  • Leaving Group (LG): Atom or group that departs with electrons.
  • Substrate: Molecule undergoing the reaction. Its structure is crucial.

Nucleophiles and Bases: Strength vs. Reactivity

When discussing nucleophiles and bases, it's important to distinguish between their inherent strength and their actual reactivity in a given reaction. These two properties are related but not always perfectly correlated. Here's a breakdown:

    • Strength (Strong/Weak): This refers to the *thermodynamic* ability of a species to react. A strong base is more thermodynamically inclined to accept a proton. A strong nucleophile is more thermodynamically inclined to attack an electrophile. This is related to the equilibrium constant for the reaction.
    • Effectiveness/Reactivity (Good/Poor): This refers to the *kinetic* ability of a species to react *at a reasonable rate*. A good nucleophile reacts quickly with an electrophile. A good base abstracts a proton quickly. This is related to the activation energy of the reaction.

Here's where the nuance lies:

    • Steric Hindrance: A bulky molecule might be a strong base (thermodynamically favored to accept a proton) but a poor nucleophile (kinetically hindered from attacking an electrophile due to its size). Tert-butoxide is a classic example. It's a very strong base, but a poor nucleophile because it's so bulky.
    • Solvent Effects: Solvents can influence the kinetic ability of a nucleophile or base. For example, a nucleophile might be strong in a polar aprotic solvent but weak in a polar protic solvent. This is because the solvent can affect the nucleophile's availability to react.

Common Nucleophiles and Bases: Strength and Reactivity

Species Nucleophile Reactivity Base Strength
OH⁻ Good Strong
RO⁻ (alkoxides) Good Strong
CN⁻ Good Strong
I⁻ Good Weak
Br⁻ Moderate Weak
Cl⁻ Moderate Weak
H₂O Poor Weak
ROH (alcohols) Poor Weak
NH₃ Moderate Weak
RNH₂ (primary amines) Good Moderate
R₂NH (secondary amines) Good Moderate
R₃N (tertiary amines) Moderate Moderate
(CH₃)₃CO⁻ (tert-butoxide) Poor Very Strong

 

Mechanisms and Factors

Feature SN1 SN2 E1 E2
Mechanism Two-step: Carbocation formation then nucleophile attack One-step: Nucleophile attack and leaving group departure Two-step: Carbocation formation then proton abstraction One-step: Base abstracts proton and leaving group departs
Kinetics First-order Second-order First-order Second-order
Substrate 3° > 2° > 1° > Me Me > 1° > 2° > 3° 3° > 2° > 1° 3° > 2° > 1°
Nucleophile/Base Weak nucleophile Strong nucleophile/base Weak base Strong base
Stereochemistry Racemization Inversion No specific outcome Anti-periplanar preferred
Carbocation Forms Does not form Forms Does not form
Example (CH₃)₃CBr + H₂O → (CH₃)₃COH + HBr CH₃Br + OH⁻ → CH₃OH + Br⁻ (CH₃)₃CBr + H₂O → (CH₃)₂C=CH₂ + HBr + H₃O⁺ CH₃CH₂Br + OH⁻ → CH₂=CH₂ + Br⁻ + H₂O

Choosing Between SN1/E1 and SN2/E2

  • Substrate: 3° favors SN1/E1; 1° favors SN2/E2; 2° depends.
  • Nucleophile/Base: Strong favors SN2/E2; weak favors SN1/E1.
  • Solvent: Polar protic favors SN1/E1; polar aprotic favors SN2/E2.
  • Temperature: Higher temperatures favor elimination.

V. Summary Table

Reaction Type Favored By Key Features
SN1 3° substrate, weak nucleophile, polar protic solvent Two-step, carbocation, racemization
SN2 1° substrate, strong nucleophile, polar aprotic solvent One-step, inversion
E1 3° substrate, weak base, polar protic solvent, high temp Two-step, carbocation, more substituted alkene
E2 Any substrate, strong base, high temp One-step, anti-periplanar, more substituted alkene

VI. Examples Illustrated

  • SN1: tert-Butyl bromide + water in ethanol → tert-butyl alcohol
  • SN2: Methyl bromide + hydroxide in acetone → methanol
  • E1: tert-Butyl bromide + trace base in ethanol at high temp → isobutylene
  • E2: Ethyl bromide + strong base in ethanol at high temp → ethene