alkyl halides (haloalkanes) · pdf file 5 5 alkyl halides: r-x the carbon center is sp3...

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  • 1

    1

    Alkyl Halides (Haloalkanes)

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    2

    CH3 CH

    Cl

    CH CH3 CH3

    Cl

    CCl Cl

    Cl

    CH3 CH

    Br

    CH2 CH2 Cl

    F

    CH2CH3

    Br Cl

    Cl

    CCl F

    Cl

    F

    CCl F

    Cl

    F

    CF

    F

    C

    F

    H

    H

    Tetrachloromethane or carbon tetrachloride

    2-Chloro-3-methylbutane 3-Bromo-1-chlorobutane

    1-Ethyl-2-fluorocyclohexane 1-Bromobutane 2-Chloropropane or

    Isopropyl chloride

    Trichlorofluoromethane (Freon-11)

    Dichlorodifluoromethane (Freon-12) 1,1,1, 2-Tetrafluoroethane

    Structure of Alkyl Halides

    Chlorofluorocarbons (CFCs) :Refrigerant Gases, Ozone Depletion

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    3Halothane (Fluothane)

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    • Most alkyl halides are liquids at room temperature.

    • Liquid alkyl halides are insoluble in water and more dense than water.

    Physical Properties of Alkyl Halides

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    Alkyl Halides: R-X

    The carbon center is sp3 hybridized in alkyl halides and the C-X bond is polarized as shown because of the greater electronegativity of the halogen.

    C δ+ δ−

    X

    Electronegativity is defined as the ability of atoms to attract shared electrons in a covalent bond ------------ leads to nucleophilic substitution in alkyl halides

    Reactions of Alkyl halidesReactions of Alkyl halides

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    Nucleophilic Substitution Reactions

    Nu:- + nucleophile

    : :

    alkyl halide R-Nu + :

    :

    : -

    substrate product halide ion

    R-X X: :

    A characteristic reaction of alkyl halides is nucleophilic substitution where a nucleophile with an unshared pair of electrons replaces the halogen.

    Nu:- : :

    : :

    : -R X X: : Substitution occurs by bond heterolysis:

    +

    bond heterolysis

    Nu: +

    electron pair from nucleophile

    R:

    Examples of Nucleophilic Substitution

    : :

    - + :

    :HO: CH3-Cl:

    : : +

    : ::

    - CH3-OH Cl:

    : ::

    - :+

    : :I CH3CH2-Cl

    : :: +

    : :

    : - CH3CH2-I Cl

    ::

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    Nucleophiles

    . A nucleophile has an unshared pair of electrons available for bonding to a positive center

    Nucleophiles may be negatively charged:

    HO , CH3O , I , NH2 - - - -::

    : :

    : :

    ::::: :

    or neutral: H2O , H3N, CH3OH

    : :

    : : :

    Nucleophiles attack electropositive center.

    Halide ion is the leaving group.

    C X δ+

    δ− The polarity of the carbon-halogen bond determines the reactivity pattern:

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    Examples

    (1) - +

    nucleophile substrate

    HO C Cl

    H3C H

    H

    product leaving group

    C OH

    H3C H

    H

    + Cl

    (2) +

    nucleophile substrate

    C Cl

    H3C H

    H

    H O

    H

    ethyloxonium ion leaving group

    C O

    H3C H

    H

    + Cl

    H

    H

    product

    C OH

    H3C H

    H

    + H3O

    H2O

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    Leaving Groups

    : The halogen is only one of many leaving groups, "L". A more general description of nucleophilic substitution is

    Nu: + R-L- R-Nu + L:-

    leaving group

    .

    A good leaving group produces a stable anion or neutral molecule. Generally, the anions (conjugate bases) of strong acids are good leaving groups

    A good leaving group in R-A .

    + H2O + A: + -

    strong acid anion very stable

    H-A H3O

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    Neutral Molecules as Leaving Groups

    .

    Poor leaving groups can be turned into good leaving groups by protonation

    Hydroxide ion is a poor leaving group because it is the anion of a weak acid, H2O.

    CH3-OH

    :a nucleophilic substitution reaction occurs

    + CH3OH

    H + H2O

    leaving groupnucleophile +

    good leaving group

    CH3OH +

    CH3OCH3 H

    : : +

    + +CH3OH H2SO4 CH3OH H

    HSO4

    In the presence of a strong acid,

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    A Mechanism for the SN2 Reaction

    The Hughes-Ingold Mechanism for the SN2 Reaction

    In their mechanism, the nucleophile attacks the carbon center on the side opposite the leaving group. As overlap develops between the orbital with the electron pair of the nucleophile and the antibonding orbital of the substrate, the bond between the carbon and the leaving group weakens.

    In 1937 Edward Hughes and Sir Christopher Ingold proposed a mechanism to explain the second order kinetics and other important features of this nucleophilic substitution reaction that were known at that time.

    C Cl H

    H H

    OH- δ− δ−

    CHO Cl

    HH

    H

    + -ClCHO H

    H H

    TS

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    SN2 reaction

    All SN2 reactions proceed with backside attack of the nucleophile, resulting in inversion of configuration at the stereogenic center.

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    15

    Examples of inversion of configuration in the SN2 reaction

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    Reaction of t-Butyl Chloride with Hydroxide: SN1 Reaction

    :

    The reaction of t-butyl chloride with sodium hydroxide in a mixture of water and acetone (to help dissolve the RCl) shows the following rate expression

    + HO- acetone

    + Cl-CH3-C-Cl CH3

    CH3

    H2O CH3-C-OH

    CH3

    CH3

    . The reaction rate depends on the concentration of t-butyl chloride, but shows no dependence on the concentration of hydroxide ion

    A reaction rate that depends on the concentration of only one reactant (to the first power) is called first-order or unimolecular.

    The symbol is SN1.

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    SN1 reaction

    + + + +

    3o 2o 1o methyl

    > > >

    most stable least stable

    C R

    R R

    C R

    R H

    C H

    R H

    C H

    H H

    Relative stabilities of carbocations

    The key features 1. The mechanism has two steps. 2. Carbocations are formed as

    reactive intermediates. 3. Reactions proceed with

    racemization at a single stereogenic center.

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    Use of the SN2 Reaction in Organic Synthesis

    .

    The conversion of one compound into another through a chemical reaction is called synthesis. The SN2 reaction is often used to convert alkyl halides into other functional groups

    for R= CH3, 1o, 2o

    X = Cl,Br, I

    Nucleophiles

    R'O-

    -

    R'C

    R'-C-O- =

    R'3N:

    N3-

    R-X

    HO-

    HS-

    :CN

    C:-

    O

    alcohols

    R-OR' ethers

    thiols

    nitriles

    RC CR' alkynes

    R-O-C-R'

    =

    esters

    R-NR'3 ammonium ion

    azides

    R-OH

    R-SH

    R-CN

    O

    R-N3

    +

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    Stereochemistry of SN2 Synthetic Reactions

    . As in all SN2 reactions, these syntheses proceed with inversion at a stereocenter

    N C + C H3C

    Br

    H3CH2C H

    (R)-2-bromobutane

    C CH3

    C CH2CH3

    HN

    (S)-2-methylbutanenitrile

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    Elimination Reactions of Alkyl Halides

    In an elimination reaction, the atoms or groups X and Y are lost from adjacent carbons forming a multiple bond.

    C X

    C Y

    C C(-XY)

    The Dehydrohalogenation Reaction

    A standard synthesis of alkenes is the dehydrohalogenation reaction of alkyl halides.

    C X

    C H

    C C (-HX)

    alkyl halide alkene

    Example: The Dehydrobromination of tert-Butyl Bromide

    tert-butyl bromide

    + NaOCH2CH3CH3C-Br CH3

    CH3 CH2=C + HOCH2CH3

    + Na+ Br- isobutene

    CH3

    CH3

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    A Beta- or 1,2-Elimination Reaction

    C

    H

    H

    H

    C

    CH3

    CH3

    Br (-HBr)

    β position α position

    The α or 1 position is the carbon with the halogen leaving group.

    CH2 C CH3

    CH3

    β α CH2 C

    CH3

    CH3

    2 1 or

    The Role of Base in Dehydrohalogenation Reactions

    This reaction is described as a beta-elimination or 1,2-elimination indicating the positions of the lost atoms or groups.

    A number of different bases may be used in the dehydrohalogenation reaction. Typical bases are potassium hydroxide in ethanol (to solubilize the alkyl halide) or sodium ethoxide in ethanol. Potassium tert-butoxide is another oxygen base that is often used in dehydrohalogenation reactions.

    KOBu-t

    Some Oxygen Bases

    KOH NaOEt

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    Mechanism of Dehydrohalogenation: The E2 Reaction

    The reaction of isopropyl bromide with sodium ethoxide in ethanol to give propene:

    isopropyl bromide +

    sodium ethoxide ethanol CH3CHCH3

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