alkyl halides why are alkyl halides reactive? consider ... biewerm/6-sn2.pdf · pdf...

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  • Alkyl Halides

    Why are alkyl halides reactive?

    Consider electron density distribution

  • Bond Polarity Allows the Bond to be Broken Easier

    When X leaves and Y attacks (concerted or sequentially) determines the type of reaction

    This process does not occur with alkanes

    (carbon-carbon bonds are difficult to break)

  • Type of Reactions that can Occur with Alkyl Halides

    Substitutions: a halide ion is replaced by another atom or ion during the reaction

    Therefore the halide ion has been substituted with another species

    Eliminations: a halide ion leaves with another atom or ion

    -no other species is added to the structure

    Therefore something has been eliminated

  • Nucleophilic vs. Electrophilic

    Lewis introduced the terms nucleophile and electrophile to describe Lewis acids and bases

    Nucleophile: a species that is attracted to the nucleus of another atom

    (therefore any species attracted to a positive charge)

    Nucleo - nucleus

    Phile - attract

    Electrophile: a species that is attracted to electrons

    (therefore attracted to a negative charge)

    Electro - electron

    Phile - attract

    **Therefore nucleophiles are often negatively charged species

    and electrophiles are positively charged species

  • Some Common Nucleophiles and Electrophiles Already Observed

    HO CH3O

    Cl Br I



    Hydroxides or alkoxides


    Amines with lone pair of electrons

    Negatively charges ions

    Or species having a lone pair of electrons


    H3C Br

    !+ !-

    Positive or partially positive sites

    Carbon is a typical electrophilic site

    (electrophilic carbon)

    When attached to a good leaving group

  • One Type of Substitution, SN2

    Substitution Nucleophilic Bimolecular (2)

    One substituent is substituted by another

    Both the original starting material and the nucleophile (which becomes part of the product) are involved in the transition state for the rate determining step

    Therefore this is a bimolecular reaction

  • Potential Energy Diagram for SN2

  • Species in a Given SN2 Reaction



    transition state


    Electron rich nucleophile reacts

    with electron poor electrophile

    A SN2 reaction is dependent upon the characteristics

    of the nucleophile and substrate (electrophile)

  • Kinetics

    A SN2 reaction is a second order reaction

    First order in respect to both the nucleophile and the electrophile

    Rate = k [CH3I][HO-]

    Both methyl iodide and hydroxide are involved in the transition state so they both are

    involved in the rate equation

  • Factors Affecting Nucleophile Characteristics

    1) Strength of nucleophile

    A strong nucleophile has a high density of electrons available to form a new bond



    Electron density plots

  • Ea Lowers with Stronger Nucleophile

  • Strength of Nucleophile is also Determined by the Polarizability

    During a SN2 reaction the nucleophile is forming a new bond

    with the electrophilic carbon

    If the nucleophilic atom is more polarizable then the new bond can form at longer distances

    Polarizability increases down the periodic table

  • Trends in Nucleophilicity

    - A species with a negative charge is a stronger nucleophile than a similar species without a negative charge. In other words, a base is a stronger nucleophile than its conjugate acid

    - Nucleophilicity decreases from left to right along a row in the periodic table. Follows same trend as electronegativity (the more electronegative atom has a higher affinity for

    electrons and thus is less reactive towards forming a bond)

    -Nucleophilicity increases down a column of the periodic table,

    following the increase in polarizability

  • 2) Solvent Effects

    Solvation impedes nucleophilicity

    In solution, solvent molecules surround the nucleophile

    the solvent molecules impede the nucleophile from attacking the electrophilic carbon

    smaller anions are more tightly solvated than larger anions in protic solvents

  • Any solvent with acidic hydrogens are protic solvents

    (usually involves O-H or N-H bonds)

    Alcohols (methanol, ethanol, etc.) and amines are therefore protic solvents

    To increase nucleophilicity of anions a solvent is necessary that does not

    impede the nucleophile (thus does not solvate the charged species)

    Use polar/aprotic solvents

    (have dipole with no O-H or N-H bonds)

    H3C C N H3C






    acetonitrile acetone dimethylformamide (DMF)

  • Remember the Rate of a SN2 Reaction is Related to the Transition State Structure

    The higher the energy of this structure, the higher the energy of activation

  • 3) Sterics of Nucleophile

    As the site of negative charge in the nucleophile becomes more sterically hindered

    the reaction becomes slower (higher energy of activation

    ethoxide anion

    tert-butoxide anion

  • Substrate (Electrophile) Factors for SN2 Reactivity

    1) Leaving group ability

    For a SN2 reaction to proceed not only is a strong nucleophile required

    but there must also be a good leaving group


    Electron withdrawing

    (polarizes C-X bond to make carbon more electrophilic)

    Needs to be stable after gaining two electrons

    (therefore not a strong base)

    As polarizability increases, rate increases

    (stabilizes the transition state)

  • Leaving Group Stability

    The stability of the leaving group is manifest in the energy diagram

    -If it is unstable the energy of the products will be high

    therefore the reaction will become endothermic and

    the equilibrium will favor the starting materials

    -In the transition state the leaving group is only partially bonded

    therefore if the energy of the leaving group is high

    the energy of the transition state will also be high

    and thus the rate will be slower

  • What makes a stable leaving group?

    Good leaving groups are WEAK bases

    Therefore the conjugate base of a strong acid can be a good leaving group

    A leaving group obtains excess electron density after the reaction

    Ability to handle the excess electron density determines the leaving group stability

  • Most Strong Nucleophiles are Poor Leaving Groups

    Since strong nucleophiles have a high electron density at the reacting site

    this makes them poor leaving groups, which need to spread out the excess

    electron density over the molecule

    There are notable exceptions

    - Primarily the halides

    I-, Br-, Cl- are good leaving groups and are also nucleophilic

  • Fluoride is the Exception

    F- is a very poor leaving group

    - Should never have F- leave in a SN2 reaction

    Due to poor polarizability of fluoride

    Same reason why fluoride is a worse nucleophile than the other halogens,

    the leaving group needs to be polarizable to lower the energy of the transition state

  • 2) Sterics of Substrate

    As the number of substituents on the electrophilic carbon increases the rate decreases

  • Consider Approach of Nucleophile

    Nucleophile must be able to react with electrophilic carbon in a SN2 reaction

    Nucleophile must be able to react with blue electrophilic carbon for reaction to proceed

  • As the Length of a Substituent Chain Increases the Sterics Do Not Increase

  • As the Bulkiness, or Branching, of a Substituent Increases

    Though the Rate Drops Dramatically

  • Stereochemistry of SN2 Reaction

    As the electrophilic carbon undergoes a hybridization change during the course of the reaction the substituents change in this view from pointing to the left in the starting material

    to pointing to the right in the product

    This is referred to as an inversion of configuration at the electrophilic carbon

    Therefore the stereochemistry changes

    (three-dimensional arrangement in space)

  • Consequence of Inversion in a SN2 Reaction

    A chiral carbon is still chiral but the chiralty is inverted

    (the R and S designation usually change

    but this depends on the priority of the new substituents)