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

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Alkyl Halides (Haloalkanes)

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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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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