8-1

Alkyl Halides & Radical Rx’sStructureNomenclaturePhysical PropertiesHalogenation of AlkanesMechanism of HalogenationAllylic HalogenationExamplesRadical additionNote the Chapter Summary and Key Rx’s

ClCl2

Δ

chapter 8

ss18 12

8-2

Chapter 8

H3C

CH3

H

H OH

CH

H3C F

HO

CH

H3CF

O

CO

H3C

H

OH

O

CO

H3C

OH

H

+

+

XH

H2 / M

Cl

IC

H

H3C D

NC

CH

H3CD

(-):CN:

CH2

OH O

HCH3

CH3

H

Br Mg CH3

δ+ δ−

LiCu

2

free radical substitution mechanism

allylicbenzylicHammondradical addition

Chapter 7

H3C

CH3

H

H OH

CH

H3C F

HO

CH

H3CF

O

CO

H3C

H

OH

O

CO

H3C

OH

H

+

+

XH

H2 / M

Cl

IC

H

H3C D

NC

CH

H3CD

(-):CN:

CH2

OH O

HCH3

CH3

H

Br Mg CH3

δ+ δ−

LiCu

2

8-48.1 Structure of ‘R-X’

haloalkane

sp3

(alkyl halide)

R-XH3C-Cl

haloarene

sp2

(aryl halide)

haloalkene

sp2

(a vinyl halide)

C

C

H H

CH3 X

X

8-58.1 Structure of ‘R-X’

Haloalkane (alkyl halide) sp3

R-X

H3C-Clmethyl chloride

R C

H

X

H1o halide

R C

H

X

R'2o halide

X

R C

R"

R'3o halide

8-6

IUPAC - halides (X) are substituentsSubstituent names: halo

fluoro, chloro, bromo, iodo

8.2 Nomenclature

#-haloalkane

#-halocycloalkane

(R)-4-bromo-1-chloro-4-fluoro-1-cyclopentenestructure ?

Br

F

Cl

8-88.3 Physical Properties

“polar covalent bond” - dipole- mismatch of electronegativity -size

H3C

C BrH3C

Hδ δ

8-9

8.4 Halogenation of Alkanes

X2 = Cl2, Br2 seldom F2 (too reactive - exothermic)or I2 (endothermic, unreactive)

hv = ultraviolet light, Δ = heat

substitution of X for H

H3C

CH3C

H3CH

+X X Δ

orhv

H3C

CH3CH3C X

H X+δ+

δ−

8-10

Substitution, products and by-products+ other R-X’s

H

CHH

H

+ Cl ClΔorhv

HC

HH Cl

H X+δ+ δ−

Cl

CHH Cl

hvCl2

Cl

C

ClH

Cl ClC

ClCl

Cl

hvCl2

hv Cl2

8-11Generally halogenation not useful - mixtures (separate)

A few rx’s are useful, e.g.:

+ Br2

ΔBr + HBr + other Br's

Others - allylic & benzylic

8-12Substitution, products and by-products

H3C CH3 + Br2hv

H3C CH2Br + HBr + diBr + etc

monobromination

bromination favors 3o > 2o > 1o

+ HBr + diBr +...

(92) (8)

CH3

CH2 + Br2

CH3

CH3

C

CH3

Br

CH3

CCH2Br

+Δ

H H H

CH3C

BrCH3

CH3C

HH

+ HBr + diBr +...

CH3

C

HCH3

CH3C

HH

+ Br2Δ

8-13Br+Br Br Brinitiation

H3CC

H3C HBr Br+

H3CC

H3C H

Br+ Br

H3CC

H3CH

HBr+

H3CC

H3C HH Br+propagation

terminationsH3C

CH3C H

Br H3CC

H3C H

Br

Br + BrBrBr

H3C

CH3C

H CH3

C CH3

H H3C

CH3C

H

CH3

C CH3

H

and/or

and/or

8-14

(92) (8)

Regioselective for 3o > 2o > 1o C-H

(57) (43)

>

>

ΔC

CH3

CH3

HHBr2

C

CH3

CH3

BrH +C

CH2Br

CH3

HH + HBr + other-Brs

ΔC

CH3

CH3

HHCl2

C

CH3

CH3

ClH +C

CH2Cl

CH3

HH + HCl + other-Cls

8-16Order of stability of R(+) / R.

R CR

R

R CH

R

R CH

H

H CH

H

>

>

>

E

R CR

R

R CH

R

R CH

H

H CH

H

>

>

>

E

same order

8-18

Selectivity 3o > 2o > 1o, but Cl and Br are different

Br2 1600 80 1Cl2 5 4 1

3o 2o 1o

major mono-X product

ΔCH3

H2C

CH3C CH3

H

+ X2

CH3H2C

CH3C CH3

X

+ HX + other R-X

Cl. more reactive less selective than Br.

8-19

Hammond’s Postulate Cl vs Br

Hammond’s Postulate: the structure of the transition state: – for an exothermic reaction looks more like the

reactants of that step

- for an endothermic reaction looks more like the products of that step

8-20

Hammond’s PostulateIn halogenation of an alkane, the rate-limiting step

is hydrogen abstraction– this step is endothermic for brominationand exothermic for chlorination.

ΔH°(kcalmol)

CH3 CH2-H + Br + H-BrCH3 CH2

+98 -88 +10

CH3 CH2-H + Cl + H-ClCH3 CH2

+98 -103 -5

8-21

Hammond’s Postulate

• transition state resembles the alkane and chlorine atom• little radical character on carbon in t.s.• regioselectivity only slightly influenced by radical

stability

For chlorination (hydrogen abstraction is exothermic):

8-22Hammond

R

C H

HR

Br

late t.s.

PE

SM prog rx Prod

stability of R. important SM prog rx Prod

PE

early t.s. - like SM

R

C H

HR

Cl

site of collision important

8-23

Halogenation (free radical substitution)

H H

+ Br2

Δ(heat)

H Br

+ H-Br

cool

H H

Br

Br

8-24Allyl Radical - resonance

CC

H2C

H

CC

H2C

H

HH

H

Br

H

H

Br2

Δ+ H-Br

Br

CH2C

H2C

H

H2CC

CH2

H

CH2C

H2C

H

8-25H

H

H

H

NBSH

Br

H

H

NBS for Br2

N-Br

O

O

N-H

O

O

HBr(trace) + Br2with progress rx

N

O

O

N

O

O

+hv

Br Brinitially

H-Br

8-26NBS for Br2

CH

H

+ HBrBr

CH3

Br2Δ

CH

H

Br

Br Br Br Br+

NBSΔ

+ H-BrN

O

O

H+

N

O

O

Br + N

O

O

CH

H

H

8-27Free Radical Stability

C

H

HC

H

HC

H

HC

H

H

CH

H

8-28

allylic

H2CC

CH2

H

benzylic

CH

H

Free Radical Stability

R CR

R

R CH

R

R CH

H

H CH

H

>

>

>

E

8-33

NBSΔ

H H

H

H

HH

H

H

H

H

H

H

H

Br

H H Cl2

hv

H

H

H

H

H

H

H

H

Br

+

HCl

+ H-Cl

H

H

H

H

8-34

Radical ADDITION - note rx conditions!!! Add H-X in the presence of peroxides

reverses normal addition“anti-Markovnikov”

H-XROOR H

X

H-XX

HMarkovnikov“normal”

H :Br

8-35

RO OR +RO OR

Radical ADDITION - note rx conditions!!! Add H-X in the presence of peroxides

reverses normal addition“anti-Markovnikov”X = Cl, Br, I

H-XROOR H

X

end

RO H X RO H + X

X X

XH X

HX

+ X

XX X X