e1&2, sn1&2

Nucleophilic Substitution and Elimination Reactions

SN2 Mechanism (Substitution, Nucleophilic, Bimolecular)

• Mechanism:

  • Characterized as a one-step process involving a backside attack on the substrate.

• Stereochemistry:

  • Results in inversion of configuration at the carbon center.

• Substrate Preference:

  • Order of preference for substitution: methyl > 1° > > 2° (3° substrates are never involved).

• Nucleophile:

  • Should be strong and small; common examples include:

  • Hydroxide (OH)

  • Alkoxides (OR)

  • Cyanide (CN)

  • Azide (N)

• Solvent:

  • Polar aprotic solvents are preferred, such as:

  • Dimethyl sulfoxide (DMSO)

  • Dimethylformamide (DMF)

  • Acetone

• Rate:

  • The rate of reaction given by the equation:
    $ext{Rate} = k[ ext{substrate}][ ext{nucleophile}]$

• Key Notes:

  • No formation of carbocation occurs in this mechanism.

  • Steric hindrance can impede the SN2 reaction, affecting the reaction's feasibility.

  • Best suited for primary carbon substrates.

• Fast Phrase:

  • "Primary + strong nuc → SN2"

SN1 Mechanism (Substitution, Nucleophilic, Unimolecular)

• Mechanism:

  • Involves a two-step process where a carbocation is formed.

• Stereochemistry:

  • Leads to racemization at the reaction center due to the planar nature of the carbocation.

• Substrate Preference:

  • Reaction order preference: 3° > 2° (1° substrates are never involved).

• Nucleophile:

  • Should be weak; common examples include:

  • Water (HO)

  • Alcohols (ROH)

• Solvent:

  • Preferably in a polar protic solvent, such as: water or alcohols.

• Rate:

  • Determined by the expression:
    $ext{Rate} = k[ ext{substrate}]$

• Key Notes:

  • Can lead to possible rearrangements during the formation of the carbocation.

  • Commonly occurs in tandem with the SN1 reaction.

• Fast Phrase:

  • "Tertiary + weak nuc → SN1"

E2 Mechanism (Elimination, Bimolecular)

• Mechanism:

  • Characterized as a one-step elimination process.

• Base:

  • Requires a strong base, such as:

  • Hydroxide (OH)

  • Alkoxides (OR)

  • Tert-butoxide (tBuO)

• Substrate Requirement:

  • Typically occurs with 2° or 3° substrates.

• Geometry:

  • Requires the anti-periplanar orientation of hydrogen atoms to the leaving group.

• Rate:

  • Expressed mathematically as:
    $ext{Rate} = k[ ext{substrate}][ ext{base}]$

• Key Notes:

  • Heat favors elimination pathways over substitution pathways.

  • Generally follows Zaitsev's rule, unless a bulky base is used, leading to the Hofmann product.

• Fast Phrase:

  • "Strong base = E2"

E1 Mechanism (Elimination, Unimolecular)

• Mechanism:

  • Involves a two-step elimination process where a carbocation is formed.

• Base:

  • Requires a weak base for the reaction to proceed, such as:

    • Water (HO)

    • Alcohols (ROH)

• Substrate Requirement:

  • Generally occurs with 3° > 2° substrates.

• Solvent:

  • Preferably in a polar protic environment.

• Key Notes:

  • Possible rearrangements of carbocation may occur.

  • Frequently occurs alongside SN1 reactions.

• Fast Phrase:

  • "Tertiary + weak base + heat → E1"

Quick Decision Table

• Primary + strong nucleophile → SN2

• Primary + bulky base → E2

• Tertiary + weak nucleophile/base → SN1/E1

• Tertiary + strong base → E2

• Secondary + strong nucleophile → SN2/E2 mix

• Heat → favors elimination (E1/E2)

Memory Tips

• Strong nucleophile correlations:

  • Strong = SN2/E2

• Weak nucleophile correlations:

  • Weak = SN1/E1

• Substrate correlations:

  • Primary substrates prefer SN2

  • Tertiary substrates prefer SN1/E1 or E2

• Heat influence:

  • Heat favors elimination pathways over substitution pathways.