Free Radical Reactions

Free Radical → any atoms or groups of atoms that has one or more unpaired
electrons. They usually has do not have a positive or negative charge, but are highly
reactive and short lived reaction intermediates

homolytic bond cleavage of σ bond

Production of Radicals
Homolysis of relatively weak bonds such as O-O or X-X bonds can occur
with addition of energy in the form of heat or light

Sec. 12 - free radicals 1

 Homolytic Bond Dissociation Energies and Heats of Reaction
The homolytic bond dissociation energy is abbreviated DHo

The more stable the bond the more energy required to cleave the covalent bond

Homolytic Bond Dissociation energies can be used to calculate the enthalpy

change (DHo) for a reaction

DHo is positive for bond breaking and negative for bond forming
Example
This reaction below is highly exothermic since DHo is a large and
negative
DHo is not dependant on the mechanism; only the initial and final states
of the molecules are considered in determining DHo

Sec. 12 - free radicals 2

 Free Radical Reactions

Initiation

Cl Cl + 246 kJ mol-1 2 Cl

Propagation: The initial formation of a few radicals results in the propagation of

new radicals in a self perpetuating reaction called a chain reaction.

Termination: The formation of stable

Cl + H CH3 molecules

CH3 + Cl Cl Cl + CH3

Cl + H CH2Cl CH3 + CH3

etc.
CH2Cl + Cl Cl

etc.

Sec. 12 - free radicals 3

 Hydrogen Abstraction
Hydrogen abstraction is usually the rate determining step. The reaction does not
follow 1st or 2nd order kinetics because of cyclical process.

CH4 + Cl CH3 + HCl 12 times faster

C-D is a stronger bond than C-H bond
CD4 + Cl CD3 + DCl

Stability of Radicals
Which hydrogen is extracted?
Look at the stability of the
transition state. The abstraction
of a hydrogen that produces a
more stable radical (lower ∆G‡) is
more likely to occur.
Remember the transition state
for an endergonic reaction
looks very much like the
product. Any bonds that are
forming are more than half
formed, and any bonds that are
breaking are more than half
broken
Sec. 12 - free radicals 4
 Radical stability parallels cation stability

Methyl 1° 2° 3° allylic and

benzylic
Increasing rate of reaction towards Br2
3°

benzylic

allylic

Halogen Reactivity
I2 < Br2 < Cl2 < F2

I2 Forms stable radicals F2

1° Explosive
Not due to halogen cleavage
I2 Br2 Cl2 F2
2°
Bond 151 193 243 159
dissociation (kJmol-
1
)

Sec. 12 - free radicals 5

 Order of reactivity depends on Eact for the propagation steps.
First lets define Activation Energy Eact

The Overall Free­Energy Change: ∆Go = ∆Ho ­ T (∆So)
In radical reactions such as the chlorination of methane the overall 
entropy change (∆So) in the reaction is small and thus it is appropriate to 
use ∆Ho values to approximate ∆Go values (∆Go ~ ∆Ho)
∆Go = ­102 kJ mol­1 and ∆Ho = ­101 kJ mol­1 for this reaction

Activation Energies
When using enthalpy values (∆Ho) the term for the difference in energy between 
starting material and the transition state is the energy of activation (Eact)
Recall when free energy of activation (∆Go) values are used this difference is ∆ G‡

Sec. 12 - free radicals 6

 Energy of activation values can be predicted
A reaction in which bonds are broken will have Eact > 0 even if a stronger bond is
formed and the reaction is highly exothermic
Bond forming always lags behind bond breaking

An endothermic reaction which involves bond breaking and bond forming 
will always have Eact > ∆Ho

Sec. 12 - free radicals 7

A gas phase reaction in which only bond homolysis occurs has ∆Ho = Eact

A gas phase reaction in which small radicals combine to form a new bond 
usually has Eact = 0

Sec. 12 - free radicals 8

 Back to the Order of reactivity of the Halogens which depends on
Eact for the rate determining step in the propagation steps.
Initiation
F2 + 159 kJ mol-1  2F • ∆H = 159 kJ mol-1 Eact = 159 kJ mol-1
Propagation
rate determining
F• + CH4 → HF + •CH3 + 130 kJ mol-1 ∆H = - 130 kJ mol-1 Eact = 5 kJ mol-1 step

•CH3 + F2 → CH3F + F• + 302 kJ mol-1 ∆H = - 302 kJ mol-1 Eact = small

CH4 + F2 → CH3F + HF ∆H = - 432 kJ mol-1

Explosive because Eact is low and the heat produced by the exothermic reaction
increases the rate of reaction.
Initiation
I2 + 151 kJ mol-1  2I • ∆H = 151 kJ mol-1 Eact = 151 kJ mol-1
Propagation
rate
I• + CH4 + 142 kJ mol-1 → HI + •CH3 ∆H = 140 kJ mol-1 Eact = 142 kJ mol-1 determining
step
•CH3 + I2 → CH3I + I• + 89 kJ mol-1 ∆H = - 89 kJ mol-1 Eact = small

CH4 + I2 → CH3I + HI ∆H = 53 kJ mol-1

The propagation steps are overall endothermic.

The I radical is stable and does not
Sec.abstract hydrogens.
12 - free radicals 9
 Chlorination is more reactive than Bromination

Potential Energy
CH3 + HCl ∆H = 8 kJ mol-1

CH4 + Cl ∆H = -109 kJ mol-1

(+Cl2)
∆H = -101 kJ mol-1

CH3Cl + Cl
Reaction Coordinate
Potential Energy

CH3 + HBr
∆H = 74 kJ mol-1
(+Br2) ∆H = -100 kJ mol-1

CH4 + Br ∆H = -26 kJ mol-1

CH3Br + Br
Reaction Coordinate
Sec. 12 - free radicals 10
 Mono Halogenation of higher alkenes and the selectivity differences
between Chlorination and Bromination
2 Br Br
Br
hv CH3CH2CH2 + CH3CHCH3 + HBr CH3CH2CH2Br + CH3CHCH3
CH3CH2CH3 + Br2
1° 2° 98 %

2 Cl Cl
Cl
hv CH3CH2CH2 + CH3CHCH3 + HCl CH3CH2CH2Cl + CH3CHCH3
CH3CH2CH3 + Cl2
1° 2° 55 %

Bromination is more selective than chlorination because it is less reactive.

There are only a few bromine radicals that have enough energy to abstract a hydrogen
that will produce the less stable molecule. Thus a greater number of the more stable
intermediates are produced in the reaction. This creates the selectivity in the reaction.

The chlorine radical being more reactive will produce more of the unstable
intermediate, thus producing more of a mixture of products. Fluorine being much more
reactive than chlorine is even less selective and there is little difference between the
rate of abstracting a 1°, 2° or 3° radicals.

Sec. 12 - free radicals 11

 What are the major products formed in the following reactions

CH3
Br2
H3C C CH3
hv, 127°
H

CH3
Cl2
H3C C CH3
hv, 25°
H

Br2
hv

Note: Radicals do not rearrange.

Sec. 12 - free radicals 12

 Stereochemistry of an alkyl radical

Cl
H
Cl2 H3CH2C
C C CH2Cl Cl
H3CH2C hv
H3C
H3C CH2Cl

(-)-1-chloro-2-methylbutane (±)-1,2-dichloro-2-butane
radical intermediate (a racemic form)

Halogenation of butane
C
Br (S)

Br
HBr +
1 equiv.
Br (R)
C

Sec. 12 - free radicals 13

Now chlorinate at C3

Br C C

Cl C
H C 2(S) H
1 equiv.
CH3
H3C C
C

steric hindrance from

CH3 bottom less product
H Br Cl2 Diastereomers
+
H H May not be equally
produced
CH3

If we did the same thing with (2R)- CH3CH2CHBrCH3 the results would be:

Sec. 12 - free radicals 14

If we did the same thing with (2R) - CH3CH2CHBrCH3 the results would be:

(2R)-2-bromobutane → (2R,3R)-2,3-bromochlorobutane (60%)

+ (2R,3S)-2,3-bromochlorobutane (40%)

+ +

Which compounds are enantiomers?

Would this solution be optically active?

Sec. 12 - free radicals 15

Sec. 12 - free radicals 16