About The Authors

Chapter 10
These Powerpoint Lecture Slides were created and prepared by Professor
William Tam and his wife Dr. Phillis Chang.

Professor William Tam received his B.Sc. at the University of Hong Kong in
1990 and his Ph.D. at the University of Toronto (Canada) in 1995. He was an
NSERC postdoctoral fellow at the Imperial College (UK) and at Harvard
University (USA). He joined the Department of Chemistry at the University of
Radical Reactions Guelph (Ontario, Canada) in 1998 and is currently a Full Professor and
Associate Chair in the department. Professor Tam has received several awards
in research and teaching, and according to Essential Science Indicators, he is
currently ranked as the Top 1% most cited Chemists worldwide. He has
published four books and over 80 scientific papers in top international journals
such as J. Am. Chem. Soc., Angew. Chem., Org. Lett., and J. Org. Chem.

Dr. Phillis Chang received her B.Sc. at New York University (USA) in 1994, her
Created by M.Sc. and Ph.D. in 1997 and 2001 at the University of Guelph (Canada). She
lives in Guelph with her husband, William, and their son, Matthew.
Professor William Tam & Dr. Phillis Chang
Ch. 10 - 1 Ch. 10 - 2

1. Introduction: How Radicals Form 1A. Production of Radicals

and How They React

Heterolysis
Homolysis of covalent bonds
heterolytic ● Need heat or light (hν)
A B bond
A + B
(alkoxyl radical)
cleavage heat
ions R O O R 2R O

Homolysis
homolytic (chlorine radical)
A B bond
A + B Cl Cl
hν
2 Cl
cleavage radicals
Ch. 10 - 3 Ch. 10 - 4

1B. Reactions of Radicals 2. Homolytic Bond Dissociation

Almost all small radicals are short-lived, Energies (DH°)
highly reactive species H + H H H
o
∆H = −436 kJ/mol Bond formation is
an exothermic
substitution
Cl + Cl Cl Cl process.
Cl + H CH3 Cl H + CH3 o
∆H = −243 kJ/mol

H H H + H
R o Reactions in which
∆H = +436 kJ/mol
addition only bond breaking
R + C C C C
Cl Cl Cl + Cl occurs are always
o endothermic.
∆H = +243 kJ/mol
Ch. 10 - 5 Ch. 10 - 6

Single-Bond Homolytic Dissociation
energy must be be supplied to break covalent bonds
Energies (DH°) at 25°C

The energies required to break Bond Broken kJ/mol
covalent bonds homolytically are called
homolytic bond dissociation H–H 436
energies, and they are usually F–F 159
abbreviated by the symbol DH °
Cl–Cl 243

Br–Br 193

I–I 151
Ch. 10 - 7 Ch. 10 - 8

Single-Bond Homolytic Dissociation
Single-Bond Homolytic Dissociation

Energies (DH°) at 25°C Energies (DH°) at 25°C

Bond Broken kJ/mol Bond Broken kJ/mol Bond Broken kJ/mol

H–F 570 H3C–H 440

H–Cl 432 H3C–F 461

H–Br 366 H3C–Cl 352

H–I 298 H3C–Br 293 H3C–OH 387

H3C–I 240 H3C–OCH3 348

Ch. 10 - 9 Ch. 10 - 10

Single-Bond Homolytic Dissociation
Single-Bond Homolytic Dissociation

Energies (DH°) at 25°C Energies (DH°) at 25°C
Bond Broken kJ/mol Bond Broken kJ/mol Bond Broken kJ/mol Bond Broken kJ/mol

H H
Cl Br 423 369
354 294

H 413 H 465
maybe they are missed place
Cl 355 Br 298
H 400 Ph H 474

Cl 349 Br 292
Ph H 375 HC C H 547
Ch. 10 - 11 Ch. 10 - 12
energy from high to low
2A. Use Homolytic Bond Dissociation
Energies to Calculate Heats of Reaction
o
(DH = 432 kJ/mol) ☓ 2
o o ∆H = −2 (432 kJ/mol) + (436 kJ/mol + 243 kJ/mol)
(DH = 436 kJ/mol)
o
= −864 kJ/mol + 679 kJ/mol
(DH = 243 kJ/mol) = −185 kJ/mol

H H + Cl Cl 2H Cl
Overall, the reaction of 1 mol of H2 and

+679 kJ is required -864 kJ is evolved 1 mol of Cl2 to form 2 mol of HCl is
to cleave 1 mol of in formation of exothermic
H2 bonds and bonds in
1 mol of Cl2 bonds 2 mol of HCl

Ch. 10 - 13 Ch. 10 - 14

2B. Use Homolytic Bond Dissociation

Energies to Determine the Relative
Stabilities of Radicals
+ H
∆Ho = +423 kJ/mol
tert-Butyl radical
H + H ∆Ho = +400 kJ/mol
(a 3o radical)
Propyl radical H
o
(a 1 radical) H

∆Ho = +413 kJ/mol + H

Isobutyl radical
+ H ∆Ho = +422 kJ/mol
(a 1o radical)
Isopropyl radical
H
(a 2o radical)
Ch. 10 - 15 Ch. 10 - 16

Relative Stability 3. The Reactions of Alkanes with

● Carbon radicals are considered to Halogens
be electron deficient (similar to
carbocations), thus electron
Alkanes have no functional group and
donating groups stabilize radicals are inert to many reagents and do not
undergo many reactions
 3o > 2o > 1o

Halogenation of alkanes is one of the
CH3 H H H
most typical free radical reactions
CH3 C CH3 > CH3 C CH3 > CH3 C H>H C H

(positive inductive effect of alkyl groups stabilize radical)

Ch. 10 - 17 Ch. 10 - 18
 general

Alkanes react with molecular halogens 3A. Multiple Halogen Substitution
to produce alkyl halides by a
substitution reaction called radical H
heat
H Cl
halogenation H C H + Cl2 H C Cl + H C Cl
or
H light H H
heat
R H + X2 R X + H X Cl Cl
or
light (hν) + Cl C Cl + Cl C Cl
H Cl
not good from pov
cuz multiple product formations
+
radival is very reactive intermediate that we can H Cl
not control sometimes form intermediates
instead of final product
Ch. 10 - 19 so we have a mixture of product as we dont Ch. 10 - 20
have selectivity

3B. Lack of Chlorine Selectivity Polichlorinated

Cl2
Cl + + products + HCl

Chlorination of most higher alkanes light
Cl (23%)
gives a mixture of isomeric monochloro Isobutane Isobutyl tert-Butyl
chloride chloride
products as well as more highly (48%) (29%)
halogenated compounds
● Chlorine is relatively unselective; ● Because alkane chlorinations
it does not discriminate greatly usually yield a complex mixture of
among the different types of products, they are not useful as
hydrogen atoms (primary, synthetic methods when the goal is
secondary, and tertiary) in an preparation of a specific alkyl
alkane chloride
Ch. 10 - 21 Ch. 10 - 22

heat
● An exception is the halogenation of + Cl2
Cl
+ H Cl
an alkane (or cycloalkane) whose or
Neopentane light Neopentyl
hydrogen atoms are all equivalent.
(excess) chloride
[Equivalent hydrogen atoms are
defined as those which on
replacement by some other group ● Bromine is generally less reactive
(e.g., chlorine) yield the same toward alkanes than chlorine, and
compound.] bromine is more selective in the
site of attack when it does react

Ch. 10 - 23 Ch. 10 - 24
4. Chlorination of Methane:
Mechanism of Free Radical Chlorination
Mechanism of Reaction of CH4
(1) Chain initiation

Most radical reactions include 3 stages
(steps)
formation of radicals
hν
(1) chain initiation Cl Cl 2 Cl
(2) chain propagation formation of radicals (homolytic
(combination of
(3) chain termination radicals )stop gwoing
cleavage)
of radicals

● Radicals are created in this step

initiation is always endothermic cux we break bonds

ot alwyas endo then exo Ch. 10 - 25 Ch. 10 - 26
but you have to have exothermic for the reaction to occur

(2) Chain propagation (2) Chain propagation

H
● Other than CH3Cl, other
(i) Cl + H C H H Cl + CH3
chlorination products can be formed
H in the chain propagation step
Cl
(ii) CH3 + Cl Cl CH3Cl + Cl
(ia) Cl + H C H H Cl + CH2Cl
● Repeating (i) and (ii) in a chain
reaction provides the product CH3Cl H

● In chain propagation, one radical

generates another and the process
(II) imp to contiune the chain of our alkane
(iia) CH2Cl + Cl Cl CH2Cl2 + Cl
goesouron
radical now is responsible and able to provide more Cl atoms
once we start the reaction we continue
Ch. 10 - 27 repeating the steps of (i) (ii) Ch. 10 - 28
step 2 can be repeated

stop growing radicals chains that occur in (2)

(2) Chain propagation (3) Chain termination

Cl
(ib) Cl + H C Cl H Cl + CHCl2
Cl + CH3 Cl CH3
H

(iib) CHCl2 + Cl Cl CHCl3 + Cl

CH3 + CH3 H3C CH3

Cl Cl + CH2Cl2
CH2Cl
(ic) Cl + H C Cl H Cl + CCl3
Cl
CHCl2 + CCl3 Cl2HC CCl3
(iic) CCl3 + Cl Cl CCl4 + Cl mixture of product
Ch. 10 - 29 Ch. 10 - 30
 (3) Chain termination e.g.:
● Free radical reactions cannot be
completed without chain CH4 (large excess) + Cl2
termination hν
● All radicals are quenched in this CH3Cl (mainly)
step
● Radical reactions usually provide
CH4 + Cl2 (large excess)
mixture of many different products
● Synthesis of CH3Cl or CCl4 is hν
possible using different amounts of CCl4 (mainly)
reactants (CH4 and Cl2)
Ch. 10 - 31 Ch. 10 - 32

5. Chlorination of Methane:
Chain propagation

Energy Changes Step 2 H3C H + Cl CH3 + H Cl
o o
(DH = 440) (DH = 432)

Chain initiation o
∆H = +8 kJ/mol
Step 1 Cl Cl 2 Cl
(DHo = 243) Step 3 CH3 + Cl Cl H3C Cl + Cl
∆Ho = +243 kJ/mol
o o
(DH = 243) (DH = 352)
∆Ho = −109 kJ/mol

Ch. 10 - 33 Ch. 10 - 34

Chain termination
The addition of the chain-propagation

steps yields the overall equation for the
CH3 + Cl H3C Cl ∆Ho = −352 kJ/mol chlorination of methane
(DHo = 352)
H3C H + Cl CH3 + H Cl
o o
CH3 + CH3 H3C CH3 ∆H = −378 kJ/mol ∆H = +8 kJ/mol
o
(DH = 378)
CH3 + Cl Cl H3C Cl + Cl
o
Cl + Cl Cl Cl ∆H = −243 kJ/mol ∆Ho = −109 kJ/mol
(DHo = 243)
H3C H + Cl Cl H3C Cl + H Cl
o
∆H = −101 kJ/mol
Ch. 10 - 35 Ch. 10 - 36
5A. The Overall Free-
Free-Energy Change CH4 + Cl2 → CH3Cl + HCl

2 mol of the products are formed from the
o o
∆G = ∆H – T ∆S
o same number of moles of the reactants
● Thus the number of translational
degrees of freedom available to

For many reactions the entropy change products and reactants is the same
is so small that the term T ∆S o in the
CH3Cl is a tetrahedral molecule like CH4, and
above expression is almost zero, and HCl is a diatomic molecule like Cl2
o
∆G is approximately equal to ∆H
o ● This means that vibrational and
rotational degrees of freedom available
to products and reactants should also be
approximately the same
Ch. 10 - 37 Ch. 10 - 38

CH4 + Cl2 → CH3Cl + HCl 5B. Activation Energies

A low energy of activation means a reaction


o
∆S = +2.8 J K-1 mol-1 will take place rapidly; a high energy of
activation means that a reaction will take
place slowly

At room temperature (298 K) the T∆S o
Chain initiation
term is 0.8 kJ mol-1
Step 1 Cl2 → 2 Cl •
Eact = +243 kJ/mol
o Chain propagation

∆H = −101 kJ mol-1
Step 2 Cl • + CH4 → HCl + CH3 •
Eact = +16 kJ/mol

∆G o = −102 kJ mol-1 Step 3 Cl • + Cl2 → CH3Cl + Cl •
Ch. 10 - 39 Eact = ~8 kJ/mol Ch. 10 - 40

Estimates of energies of activation
Estimates of energies of activation

(1) Any reaction in which bonds are (2) Activation energies of endothermic
broken will have an energy of activation reactions that involve both bond
greater than zero. This will be true even formation and bond rupture will be
if a stronger bond is formed and the greater than the heat of reaction, ∆H o
reaction is exothermic. The reason:
H3C H + Cl CH3 + H Cl
Bond formation and bond breaking do o o
not occur simultaneously in the (DH = 440) ∆H = +8 kJ/mol (DHo = 432)
Eact = +16 kJ/mol
transition state. Bond formation lags
behind, and its energy is not all
available for bond breaking H3C H + Br CH3 + H Br
o o
(DH = 440) ∆H = +74 kJ/mol (DHo = 366)
Eact = +78 kJ/mol
Ch. 10 - 41 Ch. 10 - 42

Estimates of energies of activation
(3) The energy of activation of a gas-
phase reaction where bonds are broken
homolytically but no bonds are formed
is equal to ∆H o
Cl Cl 2 Cl o
∆H = +243 kJ/mol
(DHo = 243) Eact = +243 kJ/mol

Ch. 10 - 43 Ch. 10 - 44

Estimates of energies of activation 5C. Reaction of Methane with Other

(4) The energy of activation for a gas- Halogens
phase reaction in which small radicals FLUORINATION
combine to form molecules is usually o
∆H Eact
zero (kJ/mol) (kJ/mol)
2 CH3 H3C CH3 o
∆H = − −378 kJ/mol Chain initiation
o Eact = 0
(DH = 378)
F2 → 2 F • +159 +159
Chain propagation
F • + CH4 → HF + • CH3 −130 +5.0
• CH3 + F2 → CH3F + F • −302 small
o
Overall ∆H = −432
Ch. 10 - 45 Ch. 10 - 46

CHLORINATION BROMINATION
o o
∆H Eact ∆H Eact
(kJ/mol) (kJ/mol) (kJ/mol) (kJ/mol)
Chain initiation Chain initiation
Cl2 → 2 Cl • +243 +243 Br2 → 2 Br • +193 +193
Chain propagation Chain propagation
Cl • + CH4 → HCl + • CH3 +8 +16 Br • + CH4 → HBr + • CH3 +74 +78
• CH3 + Cl2 → CH3Cl + Cl • −109 small • CH3 + Br2 → CH3Br + Br • −100 small
o o
Overall ∆H = −101 Overall ∆H = −26

Ch. 10 - 47 Ch. 10 - 48
 6. Halogenation of Higher Alkanes
IODINATION
∆H
o
Eact
Mechanism for radical halogenation of
(kJ/mol) (kJ/mol) ethane
Chain initiation Chain initiation
light
I2 → 2 I • +151 +151 Step 1 Cl2 2 Cl
or heat
Chain propagation
I • + CH4 → HI + • CH3 +142 +140 Chain propagation
• CH3 + I2 → CH3I + I • −89 small Step 2 CH3CH2 H + Cl CH3CH2 + H Cl
o
Overall ∆H = +53
Step 3 CH3CH2 + Cl Cl CH3CH2 Cl + Cl
Ch. 10 - 49 Ch. 10 - 50

compare

propane Cl
Cl2
Cl +
Chain termination light
25oC
isobutane the teriary will be the more selective
product
CH3CH2 + Cl CH3CH2 Cl Cl2
Cl +
light Cl
25oC
CH3CH2 + CH3CH2 CH3CH2 CH2CH3
Cl2
Cl +
300oC Cl

Cl + Cl Cl Cl + +
Cl

Ch. 10 - 51 Cl Ch. 10 - 52

more selectivity than chlorination

6A. Selectivity of Bromine
Mechanism
hν

Bromination is slower than chlorination Br Br 2 Br
because the 1st propagation step is
more endothermic (overall still
H
exothermic). As a result, bromination Br + H Br
is more selective than chlorination
(major; 3o radical more stable)
hν H
H + Br2 Br
+
Br H
H
Br + H Br
(99%) (< 1%) H
teriary primary (minor; 1o radical less stable)
Ch. 10 - 53 Ch. 10 - 54
 you have to mentiond the main and the minor teriary

Mechanism products as the ratio different (3:1 etc)

Br2
Br +
Br hν Br
Br (major)
127oC (trace) (> 99%)
= few

Cl2 Cl +
H H
Br (minor) hν Cl
Br o (63%) (37%)
25 C
primary

Ch. 10 - 55 Ch. 10 - 56

7. The Geometry of Alkyl Radicals 8. Reactions That Generate

Tetrahedral Chirality Centers
p-orbital Cl
Cl2 Cl
+ *
R achiral
R C Pentane 1-Chloropentane ( )-2-Chloropentane
R (achiral) (achiral) (a racemic form)

+
sp2 hybridized
Cl

Planar, similar to carbocation 3-Chloropentane
(achiral)

Ch. 10 - 57 Ch. 10 - 58

The Stereochemistry of chlorination at 8A. Generation of a Second Chirality

C2 of pentane C2 Center in a Radical Halogenation
CH3CH2CH2CH2CH3
diastereomers
Cl Cl Cl
Cl2
Cl 2 3 2 3 + 2 3
hν
+ Cl + Cl H H Cl Cl
CH3
CH3 H3C (S)-2- (2S,3S)- (2S,3R)-
Cl2 Cl2
C Chloropentane Dichloropentane Dichloropentane
Cl H H Cl
(a) (b) (chiral) (chiral) (chiral)
CH2CH2CH3 H3CH2CH2C
H CH2CH2CH3
(S)-2-Chloropentane trigonal planar (R)-2-Chloropentane Cl from bottom Cl2 from top Cl2
(50%) radical (achiral) (50%) face face

enantiomers trigonal planar

Ch. 10 - 59 H Ch. 10 - 60
 9. Radical Addition to Alkenes: The
Anti-Markovnikov Addition of
Hydrogen Bromide

Anti-Markovnikov addition of HBr to

Note that other products are formed, alkenes – peroxide effect
of course, by chlorination at other ● Addition of HBr to alkenes usually
carbon atoms follows Markovnikov’s rule

Br H not H Br
HBr

Ch. 10 - 61 Ch. 10 - 62

● In the presence of peroxides (RO–
Mechanism

OR), anti-Markovnikov addition is ● Via a radical mechanism
observed
heat
RO OR 2 RO
H Br not Br H (homolytic cleavage)
HBr
(chain initiation)
RO OR
heat
RO + H Br ROH + Br

Ch. 10 - 63 Ch. 10 - 64

Synthetic application
Br +
Br Br
o
(3 radical, more stable) HBr

Br (via more stable

2o carbocation)
not Br +

(1o radical, less stable) HBr Br

H RO-OR
heat (via more stable
+ H Br + Br
2o radical)
Br Br Ch. 10 - 65 Ch. 10 - 66

Hydrogen bromide is the only hydrogen 10. Radical Polymerization of
halide that gives anti-Markovnikov Alkenes: Chain-Growth Polymers
addition when peroxides are present
peroxide

Hydrogen fluoride, hydrogen chloride, n CH2 CH2 CH2CH2
heat n
and hydrogen iodide do not give anti-
(monomer) (polymer)
Markovnikov addition even when
peroxides are present

Ch. 10 - 67 Ch. 10 - 68

Via radical mechanism

∆ (v) RO CH2CH2 CH2CH2 + OR
(i) RO OR 2 RO 2

(ii) RO + H2C CH2 RO CH2CH2 RO CH2CH2 CH2CH2OR

n

(iii) RO CH2CH2 + H2C CH2

(vi) RO CH2CH2 CH2CH2
RO CH2CH2CH2CH2 n

+ RO CH2CH2 CH2CH2
(iv) RO CH2CH2CH2CH2 + H2C CH2 n

RO CH2CH2 CH2CH2 RO CH2CH2 OR

2 Ch. 10 - 69 x
Ch. 10 - 70

Other common polymers
Other common polymers

ROOR
n CH2 CHCH3 CH2CH CH3 CH3
∆ ROOR
Polypropylene CH3 n n CH2 C CH2C
∆
COOMe COOMe
n
ROOR Polymethyl methacrylate
n CH2 CHCl CH2CH
∆ (windshield, contact lenses)
PVC (plumbing polymer) Cl n
ROOR
n CH2 CHPh CH2CH
ROOR ∆
n CF2 CF2 CF2CF2 Ph
∆ n Polysterene (styrofoam, n
Polytetrafluroethene (Teflon) coffee cup, etc.)
Ch. 10 - 71 Ch. 10 - 72
 END OF CHAPTER 10 

Ch. 10 - 73