RADICAL REACTIONS

Objectives

 Understand the properties of radicals

 How are radicals formed
 Understand the reactivity of radicals
 Understand the importance of radical based reactions in nature

What are radicals?

Species with unpaired electrons are called radicals.
They are involved in the chemistry of burning, aging, disease as well as in reactions related to the
destruction of the ozone layer and synthesis of products that enhance our everyday lives. For example
polyethylene (polyethene, which can have a molecular weight from thousands to millions, and
practical uses of ranging from plastic films and wraps to water bottles, bulletproof vests and, hip and
knee replacements, is made by a reaction involving radicals. Insert text! remove
Production of radicals
Energy in form of heat or light must be supplied to cause homolysis of covalent bonds.
For example, compounds with an oxygen-oxygen bond, called peroxides, undergo homolysis readily
when heated, because the oxygen-oxygens bond is weak. The products are two radicals, known as
alkoxyl radicals:

Homolysis of a dialkyl peroxide

Homolysis
R O O R
heat
2 R O

dialkyl peroxide alkoxyl radicals

Homolysis of a halogen atom

Homolysis
X:X X
heat or light
h

The products of this homolysis are halogen atoms, and because halogen atoms contain an unpaired
electron, they are radicals.

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REACTION OF RADICALS
 Almost all small radicals are short lived, highly reactive species.
When radicals collide with other molecules, they tend to react in a way that leads to pairing of their
unpaired electron. One way they can do this is by abstracting an atom from another molecule. To
abstract an atom means to remove an atom by homolytic bond fission (cleavage) as the atom forms a
bond with another radical. For example, and chlorine atom may abstract a hydrogen from and alkane.
This hydrogen abstraction gives the halogen atom an electron and (from hydrogen) to pair with
unpaired electron. Notice also that the other product is another radical intermediate, in this case, an
alkyl radical, R’, which goes on to react further, as shown later in this section.

Hydrogen atom abstraction

Hydrogen atom abstraction

X + H:R X H R

reactive radical Alkane alkyl radical intermediate

specific example

Cl + H CH3 Cl H + CH3

chlorine atom methane methyl radical

This behavior is characteristic of radical reactions.

Consider another example on that shows another way of in which radicals can react:
They can combine with a compound containing a multiple bond to produce a new radical, which goes
on to further, (more coverage on this type of reaction in the Chapter on alkenes).

Radical addition to a pi-bond

C C
R C C

reactive alkyl radical

intermediate alkene New radical intermedaite

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HOMOLYTIC BOND DISSOCIATION ENERGIES (DHO)
When atoms combine to form molecules energy is given out, this called exothermic reaction
When molecular bonds break energy is needed, we say energy is absorbed, this reaction is
endothermic.
For example

H + H H H Ho = - 436 kJ mol-1

Bond formation is an
exothermic process:
Ho = negative.
Cl + Cl Cl Cl Ho = - 243 kJ mol-1

Reactions in which only bond breaking occurs are always endothermic. The energy required to
breaking the covalent bond of hydrogen or chlorine homolytically is exactly equal to that evolved
when separate atoms combine to form molecules. In the bond cleavage process, DHo is positive.

H H H + H Ho = + 436 kJ mol-1

Bond breaking is an
endothermic process:
Ho = positive.

Cl Cl Cl + Cl Ho = + 243 kJ mol-1

HOW TO USE HOMOLYTIC BOND DISSOCIATION ENERGIES TO DETERMINE THE

RELATIVE STABILITIES OF RADICALS
The homolytic bond dissociation energies also provide us with a convenient way to estimate the
relative stabilities of radicals. If we examine the data given in table 1.0 below, we find the following
values of bond dissociation energies (DHo) for the primary and secondary carbon –hydrogen (C-H)
bonds of propane;

H
o -1
DH = 423 kJ mol DH o = 413 kJ mol-1

This means that for the reaction in which the designated C-H bonds are broken homolytically, the
values of ∆Ho are those given here below:

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 H + H
Ho = + 423 kJ mol-1
propyl radical

+ H
Ho = + 413 kJ mol-1

H isopropyl radical

These reactions resemble each other in two respects: They both begin with the same alkane
(Propane), and they both produce and alky radical and a hydrogen atom. They differ, however, in the
amount of energy required and in the type of carbon radical produced. These two differences are
related to each other.

 Alkyl radicals are classified as being primary, 1o, secondary, 2o, or tertiary, 3o based on the
carbon atom that has the unpaired electron, the same way that we classify carbocations based
on the carbon atom with the positive charge.
 More energy must be supplied to produce a primary alkyl radical (propyl radical) from
propane than is required to produce a secondary carbon radical (the isopropyl radical) from
the same compound. This means that the primary radical has absorbed more energy and thus
has greater potential energy. Because the relative stability of a chemical species is inversely
proportional to its potential energy, the secondary radical must be the more stable radical (Fig
1.0 below). Actually, the secondary isopropyl radical is more stable than the primary propyl
radical by 10 kJ mol-1.

TABLE: SINGLE-BOND HOMOLYTIC DISSOCIATION ENERGIES (DH) AT 25OC

BOND KJ/mol BOND KJ/mol BOND KJ/mol
BROCKEN BROCKEN BROCKEN
H-H 436 CH3CH2-OCH3 352 CH2=CH2-H 369
D-D 443 CH3CH2CH2-H 423 CH2=CH-H 465
F-F 159 CH3CH2CH2-F 444 C5H5-H 474
Cl-Cl 243 CH3CH2CH2-Cl 354 HCΞC-H 547
Br-Br 193 CH3CH2CH2-Br 294 CH3-CH3 378
I-I 151 CH3CH2CH2-I 239 CH3CH2-CH3 371
H-F 570 CH3CH2CH2-OH 395 CH3CH2CH2-CH3 374
H-Cl 432 CH3CH2CH2-OCH3 355 CH3CH2-CH2CH3 343
H-Br 366 (CH3)2CH-H 413 (CH3)2CH-CH3 371
H-I 298 (CH3)2CH-F 439 (CH3)3C-CH3 363
CH3-H 440 (CH3)2CH-Cl 355 HO-H 499
CH3-F 461 (CH3)2CH-Br 298 HOO-H 356
CH3-Cl 352 (CH3)2CH-I 222 HO-OH 214
CH3-Br 293 (CH3)2CH-OH 402 (CH3)3CO-OC(CH3)3 157
CH3-I 240 (CH3)2CH-OCH3 359 C5H5COO-OCOC6H5 139
CH3-OH 387 (CH3)2CHCH2-H 422 CH3CH2O-OCH3 184
CH3-OCH3 348 (CH3)3C-H 400 CH3CH2O-H 431
CH3CH2-H 421 (CH3)3C-Cl 349 CH3COH 364
CH3CH2-F 444 (CH3)3C-Br 292
CH3CH2-Cl 353 (CH3)3C-I 227
CH3CH2-Br 295 (CH3)3C-OH 400
Ch3CH2-I 233 (CH3)3C-OCH3 348
CH3CH2-OH 393 C6H5CH2-H 375

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‘’Data compiled from the national institute of standards(NIST) Standard reference Data base number 69, july2001 release,
accessed via NIST chemistry webBook(http://webbook.nist.gov/chemistry/) Copyright 2000. Data from CRC Handbook of
chemistry and physics, updated 3rd Electronic edition; Lide, David r, ed. DHO values were obtained directly or calculated
from heat of formation (Hf) data using the equation DHO [A-B] = Hf [A.] + Hf [B.] - Hf [A-B].’’

We can use the data in table to make a similar comparison of tert-butyl radical (a 3o radical)
and the isobutyl radical (a 1O radical) relative to isobutene:
+ Ho = +400KJ/mol
tert-butyl radical
H (a 3o radical)
H
+ Ho = +422 KJ/mol

isobutylradical
( a 1o radical)

Here we find (figure below) that the difference in stability of the two radicals is even larger.
The tertiary radical is more stable than the primary radical by 22 KJ/mol

1o Radical

1o Radical
+H
o
3 Radical
+H 2o Radical
Potential energy

22 KJ/mol
Potential energy

10KJ/mol +H
+H
ol
ol J/
m
J/ m 0
K
23
K 40 Ho = + 422 KJ/mol
+4 Ho =
+ 413 =
+
o = K J /m
o
H
H ol

(a) (b)

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The kind of pattern that we find in these examples is found with alkyl radicals generally.

 Overall, the relative stabilities of radicals are 3o >2o >1o >methyl

3o > 2o > 1o > methyl

C C C H
C C H H

C H H H

 The order of stability of alkyl radicals is the same as for carbocations.

Although the carbon atom is uncharged, the carbon that bears the odd electron is electron
deficient. Therefore the alkyl groups attached to this carbon provide a stabilizing effect
through hyper conjugation, and the more alkyl groups bonded to it, the more stable the radical
is, thus the reasons for relative stabilities of radicals and carbocations are similar.

REACTIONS OF ALKANES WITH HALOGENS

You have met the general free radical substitution reaction mechanism earlier in this section of study.
So you already know that:

 Alkanes react with molecular halogens to produce alkyl halide by a substitution reaction
called radical halogenation.
 A halogen atom replaces one or more of the hydrogens atoms of the alkane and the
corresponding hydrogen halide is formed as a by-product.
(Note that Iodine is unreactive and does not react in this way as F2, Br2 and Cl2, due to its
unfavourable reactions energetics. But F, Cl, and Br can reactive as given below.

MULTILE HALOGEN SUBSTITUTION

A complication with alkane halogenation is the multiple alkane halogenations which always occur,
unless excess alkane is used. Otherwise if we heat or irradiate an equimolar mixture of alkane plus
halogen (F2, Cl2, or Br2) with light of appropriate wavelength, a vigorous reaction occurs to give a
mixture of products, as follows:

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 H H Cl Cl H
heat or
H C H + Cl2 + H C Cl H C Cl + H C H + H Cl
Light H C Cl +

H H H Cl H hydrogen
chloromethane dichloromethane trichloromethane tetrachloromethane chloride

Note the following observations:

 The reaction is promoted by heat or light. At room temperature methane and chlorine does
not react at a perceptible rate as long as the mixture is kept away from light.
 At room temperature if the reaction mixture is irradiated with UV light a wavelength
absorbed by Cl2 they will react.
 The mixture can also react if heated in the dark to a temperature of above 100 oC.
 The light promoted reaction is highly efficient. A relatively small number of light photons
permits the formation of relatively large amounts of chlorinated product.

LACK OF CHLORINE SELECTIVITY

Chlorination of higher alkane gives a mixture of isomeric monochlorinated products as well as more
highly halogenated compounds.

 Chlorine is relatively unselective it does not discriminate greatly among the different types of
hydrogen atoms (primary, secondary, and tertiary) in an alkane.
An example is the light initiated chlorination of isobutane:

Cl2
Cl + + polychlorinated products + H-Cl
Light (23 %)
Cl
isobutane isobutyl chloride tert-butyl chloride
48 % 29 %

 Because alkane chlorinations usually yield a complex mixture of products, they are not useful
as synthetic methods when the goal is preparation of a specific alkyl chloride.

 It is useful only when the halogenation of an alkane (or cycloalkane) whose hydrogen atoms
are all equivalent (i.e., homotopic). (Homotopic hydrogen atoms are defined as those that on
replacement by some other group (e.g., chlorine) yield the same compounds).
Neopentane, for example, can form only one monohalogenation product, and the use of a large excess
of neopentane minimizes polychlorination.

heat
+ Cl2 Cl + H-Cl
or

neopentane Light
neopentyl chloride
(excess)

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  Bromine is generally less reactive toward alkanes than chlorine, and bromine is selective in
the site of attack when it does react, as shown below:
Chlorination of most alkanes whose molecules contain more than two carbon atoms gives a mixture of
isomeric monochloro products (as well as more highly chlorinated compounds). Several examples
follow The percentages given are based on the total amount of monochloro products formed in each
reaction.

Cl2 Cl
Cl
+
Light, 25oC
propane 1-chloropropane 2-chloropropane
45 % 55 %

Cl2
+
Cl
o
Light, 25 C Cl
neopentane 1-chloro-2-methylpropane 2-chloro-2-methylpropane
(excess) 63 % 37%

Cl2 Cl +
o
300 C Cl
1-chloro-2-methylbutane 2-chloro-2-methylbutane
2-methylbutane 22%
30%

+ +
Cl
Cl
2-chloro-3-methylbutane 1-chloro-3-methylbutane
33% 15 %

The ratios of products that we obtain from chlorination reactions of higher alkanes are not
identical to what we would expect if all the hydrogens atoms of the alkanes were equally reactive.
We find that there is a correction between reactivity of different hydrogens atoms and the type of
hydrogen atom (1o, 2o, or 3o) being replaced. The tertiary hydrogen atoms of an alkane are most
reactive, secondary hydrogen atoms are next most reactive and primary hydrogen atoms are the
least reactive.

THE SELECTIVITY OF BROMINE

 Bromine shows a much greater ability to discriminate among the different types of hydrogen
atoms.
 Bromine is less reactive than chlorine towards alkanes in general but bromine is more
selectivity in the site of attack.
 Bromination is selective for substitution where the most stable radical intermediate can be
formed.

8
The reaction of 2-methyl propane and bromine, for example, gives exclusive replacement of the
tertiary hydrogen atom:

Br2
+ +
h , 127oC Br
Br
>99% (trace)

A very different result is obtained when 2-methylpropane reacts with chlorine:

Cl2
+ + Cl
h , 25 oC
Cl
(37 %) (63%)

Fluorine, being much more reactive than chlorine, is even less selective than chlorine. Because the
energy of activation for the abstraction of any type of hydrogen by a fluorine atom is low, there is a
very little difference in the rate at which a 1o, 2o, or 3o hydrogens reacts with fluorine. Reactions of
alkanes with fluorine give (almost) the distribution of products that we would expect if all of the
hydrogens of the alkane were equally reactive.

THE GEOMETRY OF ALKYL RADICALS

Experimental evidence indicates that the geometric structure of most alkyl radicals is trigonal planar
at the carbon having the unpaired electron. This structure can be accommodated by sp2-hybridised
central carbon. In an alkyl radical, p orbital contains the unpaired electron.

sp3
H

H
C C H R C C
H
H
sp2 hybridized

REACTIONS THAT GENERATE TETRAHEDRAL CHIRALITY CENTERS

 When achiral molecules react to produce a compound with a single tetrahedral chirality
center, the product will be a racemic form.
This will be always true in the absence of any chiral influence on the reaction such as an
enzyme or the use of a chiral reagent or solvent.

9
Let us examine a reaction that illustrates this principle, the radical chlorination of pentane:

Cl
Cl2 Cl
+ +
achiral
Pentane Cl
(achiral) 1-Chloropentane ( _+)-2-Chloropentane
(achiral) (a racemic form) 3-Chloropentane
(achiral)

The reaction will lead to the products shown here, as well as more highly chlorinated products.( we
can use excess pentane to minimize multiple chlorinations) Neither 1-chloropentane nor 3-
Chloropentane contains a chirality center, but 2-Chloropentane does and it is obtained as a racemic
form.

THE STEREOCHEMISTRY OF CHLORINATION AT C2 OF PENTANE

CH3CH2CH2CH2CH3

Cl

CH3 H3C
CH3 Cl2 Cl2
C Cl + Cl
Cl + Cl (a) (b)
C C
H
CH2CH2CH3 H CH2CH2CH3 CH2CH2CH3
Trigonal planar (R)-2-Chloropentane
(S)-2-Chloropentane (50%)
radical
(50%) (achiral)

Enantiomers

Abstraction of a hydrogen atom from C2 produces a trigonal planar radical that is achiral. This radical
then reacts with Chlorine at either face [by path (a) or by path (b)]. Because the radical is achiral, the
possibility of reaction by either path is the same; therefore, the two enantiomers are produced in equal
amounts and a racemic form of 2-Chloropentane results.

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We can also say that the C2 hydrogens of pentane are enantiotopic because enantiomers are formed
by reaction at each C2 hydrogen.
ALLYLIC SUBSTITUTION AND ALLYLIC RADICALS

 An atom or group that is bonded to a sp3 hybridized carbon adjacent to an alkene double bond
is called an allylic group. The group is said to be bonded at the allylic position.
allylic position

allylic position
allylic position

Cl

Br
chlorine is bonded at the allylic position bromine is bonded at the allylic position

Allylic hydrogens are especially reactive in radical substitution reactions. We can synthesize allylic
halides by substitution of allylic hydrogens. For example, when propene reacts with bromine or
chlorine at higher at high temperature or under radical conditions where the concentration of the
halogen is small, the result is allylic substitution.
And on the other hand, when propene reacts with bromine or chlorine at a low temperature, an
addition reaction of the type below occurs:

high temperature X
+ X2 + HX
and low concentrationof X2

Note that at high temperature or in the presence of a radical initator) and low concentration of X2 a
substitution reaction occurs.
X
low Temp
+ X2 at low temp an addition reaction occurs
CCl4
X

To encourage this reaction towards allylic substitution we need to use reaction conditions that favour
formation of radicals and that provide a low but steady concentration of halogen.

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ALLYLIC CHLORINATION (HIGH TEMPERATURE)
Propene undergoes allylic chlorination when propene reacts in gas phase 400oC

400 oC Cl
+ Cl2 + HCl
gas phase
3-chloropropene
(allyl chloride)

The mechanism of allylic substitution is the same as the chain mechanisms for alkane halogenations
we have done earlier in the section. In chain initiation step, the chlorine molecule dissociates into
chlorine atoms.
Chain initiations step

Cl Cl 2 Cl

In the first chain propagation step the chlorine atom abstracts one of the allylic hydrogen atoms.
The radical that is produced in this step is called the allylic radical.

1st chain propagating step

H H Cl
+ Cl
an allylic radical

In the second chain propagating step the allyl radical reacts with a molecule of chlorine.

2nd chain-propagating step

Cl
+ Cl
+ Cl Cl
an allylic radical

This step results in the formation of a molecule of allyl chloride (2-chloro-1-propene) and a chlorine
atom. The chlorine atom then brings about a repetition of the first chain propagating step. The chain
reaction continues until the usual chain terminating steps consume the radicals.

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ALLYLIC BROMINATION WITH N-BROMOSUCCINIMIDE (LOW CONCENTRATION
OF BROMINE)
Propene undergoes allylic bromination when it is treated with N-bromosuccinimide (NBS) in the
presence of peroxide or light:
.
 The reaction is initiated by the formation of a small amount of bromine radical (Br ) possibly
formed by dissociation of the N-Br bond of NBS the main propagation step for this reaction
are the same as for allylic chlorination.
Mechanism:

H
+ Br + HBr

Br Br
+ Br Br +

N-Bromosuccinimide is a solid that provides a constant but very low concentration of bromine in the
reaction mixture. It does this by reacting very rapidly with the HBr formed in the substitution
reaction. Each molecule of HBr is replaced by one molecule of bromine (Br2).


Br H


N  N
O O  O O
+ H Br + Br2

molecular bromine
N-Bromosuccinimide Succinimide generated
(NBS)

Under these conditions, that is, in a non-polar solvent and with a very low concentration of bromine,
very little bromine adds to the double bond; it reacts by substitution and replaces an allylic hydrogen
atom instead. The following reaction is observed with cyclohexene as an example also of allylic
bromination with NBS.
Br

NBS, ROOR
heat

82-87 %

 Note that, NBS is a good reagent to use for allylic bromination.

Allylic radicals are stabilized by electron delocalization.
Examination of bond dissociation energy of an allylic carbon-hydrogen bond and compare it with the
bond dissociation energies of other carbon-hydrogen bonds. We see that an allylic carbon of propene
is broken with greater ease than even the tertiary carbon-hydrogen bond of isobutene and with far
greater ease than a vinylic carbon-hydrogen bond:

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 H Eact is low
X + HX

X H
+ HX Eact is high

The reason why allylic radicals are more stable than alkyl radicals is due to electron delocalization.
For example, we can draw the following contributing resonance structures and the corresponding
resonance hybrid for the allylic radical from propene:

 
contributing resonance structures resonance hybrid

Resonance delocalization of allylic radicals means that bonding of the halogen can occur at either
end of an allylic radical. With the allylic radical from propene the two possible substitutions are the
same, but unsymmetrical allylic radicals lead to products that are constitutional isomers.

BENZYLIC SUBSTITUTION AND BENZYLIC

An atom or group bonded to a sp3 hybridized carbon adjacent to a benzene ring is called a benzylic
group. The group is said to be bonded at the benzylic position.
The following are some examples;

benzylic position benzylic position Br

Cl

chlorine and bromine atoms are bonded at benzylic positions.

Benzylic hydrogens are even more reactive than allylic hydrogen in radical substitutions reactions due
to the additional delocalizations that is possible for a benzylic radical intermediate.
When methylbenzene reacts with N-bromosuccinimide (NBS) in the presence of light:
Major products shown below:

O O
CH3
N Br Light Br
+ + N H

O benzyl bromide O
methylbenzene (-bromotoluene)
(toluene) NBS
64%

END OF NOTES

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