Nucleophilic Substitutions

Electrophiles, Nucleophiles, and Leaving Groups

SN2 Mechanism

General Information

SN2: bimolecular dependent substitution reaction with nucleophile

Reaction rate=k[nucleophile][electrophile] OR Reaction rate=k[substrate][nucleophile]

  • Rate depends on the concentration of substrate (or electrophile) AND the nucleophile

  • example:

    • What will happen to the rxn rate if [nucleophile] increases by 2 and [electrophile] increases by 3?

      • rxn rate=[nucleophile]²[electrophile]³

        • multiply 2×3

        • rate of rxn increases by 6

SN2 is more prone to occur with the following conditions

  • Solvents: polar and aprotic (non-hydrogen bonding) solvents are favored for SN2 rxns

    • avoid protic solvents like alcohol and water since they are protic and hinder back-side attack

    • use aprotic solvents like DMF (dimethylformamide), acetone, or DMSO (dimethylsulfoxide)

  • Reactivity of substrate:

    • SN2 is more likely to occur if substrate contains smaller carbon groups due to backside attacks needing room to occur

    • More steric hindrance/strain negatively impacts SN2

      • Methyl (CH3) >1°>2°> > 3°

  • Favoring conditions: strong, non-bulky nucleophiles will favor SN2 reactions

Occurs in a singular step, aka no carbocation intermediate

The Reaction Mechanism

SN1 Mechanism

General Information

SN1: unimolecular dependent substitution reaction with nucleophile

Reaction rate=k[electrophile] OR Reaction rate=k[substrate]

  • due to the carbocation formation being the rate determining step (slower step than the substitution itself)

SN1 is more prone to occur with the following solvents and substrate reactivities:

  • Solvents: favored by protic (hydrogen bonding) solvents due to the solvent stabilizing the carbocation

  • Substrate reactivity:

    • 3°>2° > > 1° (due to carbocation stability)

  • Favoring conditions: non-basic, weaker nucleophiles favor unimolecular substitutions

Occurs in 2 steps: carbocation intermediate formation and final product formation

If leaving group is located on a dash or a wedge (stereochemistry involvement) and involves only one chiral center

  • Product will be racemic… but not a fully 50/50 racemic mixture (more like 70/30 or 60/40)

  • The major product will typically be the molecule with the opposite configuration as the reactant (due to backside attack being easier to achieve)

More than one chiral center being present on the molecule will yield diastereomers for the product

NOTICE: Positive ion goes on the most stabilized carbon

Solvolysis Reactions

Occurs when the solvent is used as the nucleophile, such as water, alcohol, or ammonia

Polar protic solvents/nucleophiles speed up the rate of reactions because it helps stabilize the transition state (intermediate carbocation)

Reaction occurs then in 3 steps:

  1. Leaving group leaves, creating a carbocation

  2. Solvent behaves as a nucleophile and interacts with carbocation, creating an intermediate

    • The oxygen that attaches to the carbocation obtains a plus charge, causing hydrogen atoms attached to the oxygen to become very acidic

  3. The very acidic hydrogen then leaves the intermediate to attach itself to the solvent and the end product is formed

The Reaction Mechanisms