Radical Reactions
Chapter 15
Smith
1
Introduction
• A radical is a chemical species with
a single unpaired electron in an
orbital.
• Two radicals arise when a bond is cleaved
homolytically.
Cl-Cl + heat  Cl• + Cl•
2
o
1,
o
2
and
o
3
Radicals
H
CH3
C
CH3
C CH3
CH3
C CH3
H
H
CH3
1o
2o
3o
The number of carbon atoms bonded to the carbon with the
lone electron determines the kind of radical.
Order of stability is the same as for carbocations: a tertiary radical
is more stable than a secondary radical, and a secondary radical is
more stable than a primary radical
3
Radical Reactions
• Radical reactions are initiated with heat
(D) or light (hn) and often with a
peroxide (RO-OR) initiator.
• Once formed, a radical reacts to form a
new radical.
• A radical formed by an initiation reaction
may abstract an H• radical from a C-H
bond or bond to a p electron of a p
bond. A new s bond is formed in both
cases.
4
Step 1. Initiation Reaction: Formation of chlorine radical
Cl
Cl
heat
H
2 Cl
H
H C H +
Cl
H
H C
+
H Cl
H
Step 2. Radical makes a radical: Chlorine radical reacts
to form methyl radical
or
Cl
C C
+
Cl
C C
Step 2. Radical makes a radical: Chlorine radical adds to
double bond to form a new radical
5
Two Radicals May React with
Each Other
Step 3. Termination: Radical reacts with radical
Cl
O O
+
Cl
+
Cl
Cl Cl
O O Cl
Oxygen is a radical inhibitor, it reacts with a radical such as
Cl thereby keeping it from reacting with another species.
Compounds that prevent radical reactions are called
radical inhibitors or radical scavengers.
Vitamin E is a radical scavenger.
6
Monohalogenation of Alkanes
(Replacement of one H with Br or Cl)
CH4
+ Br2
+ Cl2
heat
hn
CH3Br
+
HBr
Cl + HCl
All Hydrogens are alike, replacement of any one gives the same product.
Halogenation of an alkane is a substitution reaction.
7
Show the monohalogenation products
for the following reaction.
Cl2
heat or UV light
Cl
Cl
Cl
+
+
+
Cl
Cl
Five different H atoms produce five unique products.
Rule: We only make monohalogenation products in this course.
8
Example of a Radical Reaction
• Halogenation (bromination or
chlorination) of alkanes.
• CH4 + Br2 + heat or UV light  CH3Br +
HBr
•To do a halogenation, use a halogen (X2).
9
How do halogenation reactions
occur?
•
•
•
•
Three essential steps :
1. Radical Initiation (heat or UV light)
2. Radical Propagation (two steps)
3. Radical Termination (three ways)
10
Radical Initiation
• Halogen + heat or UV light  radical
Br2
D
or
hn
Br =
Br
Br
Initiation: Two radicals are formed by homolysis of a s bond, starting the rxn.
11
Radical Propagation
H
(a)
Br
+
homolytic clevage
of blue bond
C
H sp H
H
3
(b)
H
C H
H
H
+ H Br
sp
C H
H
2
homolytic clevage
of pink bond
+
Br Br
Br
H C H
H
+
Br
Propagation: A radical reacts with a reactant, forming a new s bond and
a radical. (A radical makes a radical in propagation sub-steps.
12
Radical Termination
(a)
(b)
Br
+
Br
H C H
H
(c) H
C H
H
Br Br
+
+
Br
H C H
H
Br
H C H
H
H
H
C
C
H
H
H
H
Termination: Two radicals combine to form a stable bond.
13
Energy Profile of Propagation
transition state [1]
CH4 + Br2 + heat
Energy
CH3Br + HBr
Ea[1]
transition state [2]
CH4 + Br
Ea[2]
DH overall
o
CH3
BrCH3
Reaction coordinate
14
Two propagation steps; the first is rate determining.
The weaker a C-H bond, the
easier it is to remove H
Increasing strength of C-H bonds
H
H C H
H
H H
H C C H
H H
CH3
H3C C H
H
CH3
H3C C H
CH3
methyl H's
primary H's
secondary H's
tertiary H's
Increasing ease of removal of H
Use this information to predict the product distribution when more
than one kind of H is present in the substrate.
15
Predict which H is easiest to
abstract in each compound.
Tertiary H is easier to remove than secondary, and secondary is
easier to remove than primary H.
16
Bromination vs Chlorination
• Bromination is slower and more
selective than chlorination.
• Selectivity is in the order IIIo > IIo
> Io, the order of radical stability.
• The selectivity of bromination can be
explained by Hammond’s postulate,
because alkyl radical formation in
bromination is endothermic and in
chlorination is exothermic.
17
Halogenation in Synthesis
• Convert alkanes (usually symmetrical) into
alkyl halides, from which alcohols, ethers
and alkenes can be formed in one step.
Br2
Br
heat
HO- (SN2)
Br
RO-
OH
OR
t-BuO (E2)
18
Make trans-1,2-dibromocyclohexane
from cyclohexene
Classroom Activity
19
Stereochemistry of Halogenation
Starting
material
Result
a. Achiral
(not chiral)
Product is achiral or a racemic mixture
b.1.Chiral
w/rxn away
from *
b.2. Chiral
w/rxn at *
center
Configuration at * (stereogenic center)
is retained
Configuration at * depends on the
mechanism of the reaction.
20
Halogenation of an Achiral Compound
+
Cl2
hn
Cl
+
1-chlorobutane
(achiral)
butane
+
Cl
Cl
(R)-2-chlorobutane (S)-2-chlorobutane
(racemic mixture of R and S enantiomers)
Halogenation of a Chiral Compound
*
Cl
+
(R)-2-chlorobutane
Br2
hn
*
Br
Cl
+
*
Cl
Br
reaction at * gives a
racemic mixure of enantiomers
+
*
*
Cl
+
*
*
Cl
Br
Br
creation of a new * gives
a pair of diastereomers
Halogenation at Io carbon away from * retains the R configuration.
21
Problems
• Work problems 15.1 through 15.18 in
Smith.
22