Chapter 8: An Introduction to Multistep Mechanisms - SN1 and E1 Reactions

Chapter 8: An Introduction to Multistep Mechanisms: SN1 and E1 Reactions and Their Comparisons to SN2 and E2 Reactions

The Bimolecular Nucleophilic Substitution (SN2) Reaction

  • Mechanism for the general SN2 reaction:

    • Reaction involves a nucleophile (Nu:) attacking a substrate (C).

    • Reaction representation:
      (extNu+extC<br>ightarrowextNu−C+extL)ag8−1( ext{Nu} + ext{C} <br>ightarrow ext{Nu-C} + ext{L}) ag{8-1}

Unimolecular Nucleophilic Substitution (SN1) Reaction: Intermediates, Overall Reactants, and Overall Products

  • Mechanism for the general SN1 reaction:

    • Process involves the leaving group departing before the nucleophile attacks.

    • Reaction representation consists of two elementary steps:

    • Step 1: Leaving group (L) departs.

    • Step 2: Nucleophile attacks the carbocation.

    (extLeavinggroup<br>ightarrowextNu:+extC+)ag8−2( ext{Leaving group} <br>ightarrow ext{Nu:} + ext{C^+}) ag{8-2}

Overall Reactants, Overall Products, and Intermediates

  • Step 1:

    • Intermediate forms as the leaving group leaves the substrate.

  • Step 2:

    • Nucleophile combines with the formed carbocation.

    • Overall reaction representation:
      (extNu:+extC−L<br>ightarrowextNu−C−+extL)( ext{Nu:} + ext{C-L} <br>ightarrow ext{Nu-C}^− + ext{L})

Free Energy Diagram of an SN1 Reaction

  • Characteristics:

    • Two energy humps indicate two elementary steps involved in the mechanism.

Bimolecular Elimination (E2) Reaction

  • Mechanism for the general E2 reaction:

    • Base (B:) abstracts a proton while the leaving group departs simultaneously.

    • Reaction representation:
      (extB+extC<br>ightarrowextC=C+extL)ag8−3( ext{B} + ext{C} <br>ightarrow ext{C=C} + ext{L}) ag{8-3}

Unimolecular Elimination (E1) Reaction

  • Mechanism for the general E1 reaction:

    • Step 1: Leaving group departs, forming a carbocation.

    • Step 2: Base abstracts a proton from the neighboring carbon, yielding an alkene.

    • Reaction representation:
      (extBase+extC<br>ightarrowextC+extL)ag8−4( ext{Base} + ext{C} <br>ightarrow ext{C} + ext{L}) ag{8-4}

Overall E1 Reaction Representation

  • Overall reaction wording according to Equation 8-4:


    • (extBase+H−C=C−L<br>ightarrowextBH+extC=C+extL)ag8−5( ext{Base} + H-C=C-L <br>ightarrow ext{BH} + ext{C=C} + ext{L}) ag{8-5}

E1 Reaction Free Energy Diagram

  • Characteristics:

    • Transition states correspond to both steps showing energy barriers between reactants and products.

Kinetics of SN2, SN1, E2, and E1 Reactions: Evidence for Reaction Mechanisms

Rate Laws for Reactions

  • The rate laws distinguish between the different mechanisms based on their reaction rates:

    • SN2:
      (extRate=kSN2[extNu−][extR−L])ag8−6( ext{Rate} = k_{SN2}[ ext{Nu}^-][ ext{R-L}]) ag{8-6}

    • SN1:
      (extRate=kSN1[extR−L])ag8−7( ext{Rate} = k_{SN1}[ ext{R-L}]) ag{8-7}

    • E2:
      (extRate=kE2[extB−][extR−L])ag8−8( ext{Rate} = k_{E2}[ ext{B}^-][ ext{R-L}]) ag{8-8}

    • E1:
      (extRate=kE1[extR−L])ag8−9( ext{Rate} = k_{E1}[ ext{R-L}]) ag{8-9}

Rate-Determining Steps

  • Definition:

    • The rate-determining step (slow step) dominates the overall reaction rate.

  • SN2 Reaction:

    • Mechanism is a single step, thus, it is the rate-determining step.

  • SN1 Reaction:

    • The first step is the slow step and thus the rate-determining step.

Comparison of the E1 and E2 Rate Laws

  • Both E1 and E2 reactions display differing rate laws based on their mechanisms:

    • E2 Rate includes both base and substrate in the rate-dependent expression:
      (extRate=KE2[extB−][extR−L])ag8−12( ext{Rate} = K_{E2}[ ext{B}^-][ ext{R-L}]) ag{8-12}

    • E1 Rate only depends on substrate:
      (extRate=KE1[extR−L])ag8−13( ext{Rate} = K_{E1}[ ext{R-L}]) ag{8-13}

Molecularity of Mechanisms

  • Definition:

    • The molecularity refers to the number of reactants in the rate-determining step:

    • Bimolecular Reactions (e.g., SN2, E2): Two reactant species in the rate-determining step.

    • Unimolecular Reactions (e.g., SN1, E1): Only one reactant species in the rate-determining step.

Theoretical Rate Laws and Transition State Theory

  • Theoretical Rate Law:

    • Rate laws derived from proposed elementary reaction mechanisms.

    • Each elementary step has a corresponding theoretical rate law.

    • General form for an elementary step where a, b indicate stoichiometric coefficients:
      (extRate(theoretical)=k[extA]a[extB]b)( ext{Rate (theoretical)} = k[ ext{A}]^a[ ext{B}]^b)

SN1 and SN2 Theoretical Rate Laws

  • Theoretical rate laws are as follows:

    • SN2:
      (extRate(theoretical)=k[extNu−]1[extR−L]1=k[extNu−][extR−L])ag8−16( ext{Rate (theoretical)} = k[ ext{Nu^-}]^1[ ext{R-L}]^1 = k[ ext{Nu^-}][ ext{R-L}]) ag{8-16}

    • SN1:
      (extRate(theoretical)=k[extR−L]1=k[extR−L])ag8−17( ext{Rate (theoretical)} = k[ ext{R-L}]^1 = k[ ext{R-L}]) ag{8-17}

Stereochemistry of Nucleophilic Substitution and Elimination Reactions

  • Differences in Stereochemical Configurations:

    • SN1 and SN2 yield potentially different stereochemical products.

    • Likewise for E1 and E2 reactions.

Stereochemistry of SN2 Reaction

  • SN2 mechanism involves:

    • Inversion of the stereochemical configuration at the carbon initially attached to the leaving group.

    • Stereospecific reaction.

Backside Attack in SN2 Reaction

  • The nucleophile attacks the substrate from the opposite side of the leaving group (backside attack):

    • Known as Walden inversion.

Frontside Attack in SN2 Reaction

  • Description of a theoretical frontside attack shows:

    • Products remain on the same side as the original substrate, which does not occur in SN2 due to steric hindrance and charge repulsion.

Stereochemistry of SN1 Reaction

  • If an SN1 reaction is conducted on a stereochemically pure substrate, a racemic mixture of both R and S enantiomers will be produced.

Ion Pair Formation in SN1 Reaction

  • Formation of an ion pair occurs when the bond to the leaving group breaks, and electrostatic interactions keep the leaving group associated with the formed carbocation.

Production of Diastereomers in SN1 Reaction

  • When multiple chiral centers exist, a mixture of products can arise due to the different approaches of the nucleophile to the planar carbocation, resulting in R and S products being formed in differing quantities.

Stereochemistry of E2 Reaction

  • E2 reactions favor configurations where the leaving group and the hydrogen atom being eliminated are in an antiperiplanar orientation to each other.

Formation of Diastereomers in E2 Reaction

  • A precise orientation of the groups affects the stability of the resulting products and their stereochemical configurations.

Reasonableness of a Mechanism: Proton Transfers and Carbocation Rearrangements

  • Mechanisms can often involve more than two elementary steps, which introduces complexity, such as proton transfer and carbocation rearrangement processes.

Avoiding Incompatible Acids & Bases

  • Strong acids should generally not appear in mechanisms under basic conditions, and vice versa, to avoid producing incompatible species.

Strong and Weak Acids and Bases Overview

  • Strong Acids: pKa < 0, examples include H3O+{H₃O^+}, CH3OH2+{CH₃OH^+_2}

  • Weak Acids: significantly weaker than H3O+{H₃O^+}

  • Strong Bases: HO−{HO^{-}}, H2N−{H₂N^{-}}

  • Weak Bases: e.g., Water, Ammonia, Halides

Solvent-Mediated Proton Transfer

  • Solvent-assisted proton transfer mechanisms are often more reasonable than direct intramolecular transfers.

Rule 3: Avoid Termolecular Steps

  • Reactions generally do not involve steps with three reactants due to low likelihood.

Carbocation Rearrangements

  • Rearrangements occur to stabilize carbocations through shifts, as losing stable carbocations is energetically disfavored.

Favorable Shifts

  • Favorable shifts (e.g., 1,2-Hydride or 1,2-Methyl shifts) will generally occur over other potential step pathways if they enhance stability.