Lecture 17 (3-28-17)
Goals:
Become familiar with reactions of radicals
Homework problems:
Chapter 11: 1, 2, 5, 7, 12, 14, 16, 20, 22, 23, 24, 31, 33, 36, 41, 45, 46
Next time: Finish Chapter 11
Chapter 11: Radicals
Radicals are reactive intermediates with one unpaired electron


Alkyl radicals do not occupy hybridized orbitals
Alkyl radicals are sp2 hybridized
p orbital
120

o
H
They are formed by homolysis of a covalent bond
H
H

Radical stability order is the same as carbocation stability:
Least stable
1o

Most stable
2o
3o
Radicals DO NOT undergo rearrangement to form more stable radicals (unlike
carbocations)
Radical Reactions:
1. Radical halogenation of alkanes

Important reaction – introduces a functional group
o Alkanes react with halogens to form alkyl halides
o Energy in the form of heat or light is required
o Only Cl2 and Br2 are used.
Cl2
H H
H
H
Cl2
Cl2
heat
or h
heat
or h
Cl
H Cl
H
heat
or h
H
Cl
Cl
1:1

When more than one type of hydrogen is present, multiple products are formed
Br2
heat
or h
Br
Br
Br
Br
major product
Mechanism of the radical chain reaction:

3 Types of Steps:
o Initiation – radical is formed
o Propagation – product is formed, byproduct is a radical so reaction continues
o Termination – two radicals form a bond, preventing propagation
pr opagat ion
pr opagat ion
initiat ion
Cl Cl
hv
Cl
Cl
H
CH3
H Cl
H3C
Cl
Cl
H3C Cl
an alkyl halide
Cl
H3C
CH3
H3C CH3
Cl
Cl
Cl
Cl
H3C
Cl
H3C Cl
an alkyl halide
termination
Selectivity in Radical Reactions

Chlorination is unselective. Is only synthetically useful if there is one type of C—H bond
present:

Bromination is selective. Can be synthetically useful if there are multiple types of C—H
bonds bonds

Usefulness of radical halogenation:
o An alkene can be formed from an alkane
Cl
Cl2, h
Br
Br2, h

K+
K
+
O
O
Stereochemistry of radical halogenation:
o If occurs at chiral carbon, get racemic mixture
Br
Br2, h
chiral reactant
achiral radical
intermediate
Br
racemic product
mixture
o If new chiral carbon is formed, get racemic mixture
Br
Br2, h
achiral reactant
achiral radical
intermediate
racemic product
mixture
o If chiral carbon is not involved, stereochemistry remains the same
Br2, h
Br
chiral reactant
chiral product
(reaction does NOT
occur at chiral carbon)
Br
Draw mechanism and products for the following reaction. Include the initiation step Indicate
stereochemistry where appropriate.
Br 2, hv
Br
mechanism:
init iation
Br
Br
2
Br
pr opagation
pr opagation
H
Br
Br
H Br
Br
Br
Br
Sample test question: Draw the radical intermediates and products for the following reaction.
Indicate stereochemistry where appropriate.
Cl
Cl
Cl2, hv
Cl
Cl
racemic
Cl
Cl
Cl
same
2 sets of enantiomers
Cl
racemic
Cl
Cl
Cl
Cl
racemic
same
racemic
Cl
2 sets of enantiomers
Cl
Radical Allylic Bromination
formed in trace
amounts from NBS
allylic hydrogens
O
N Br
H H
H Br
H
Br2
O
HBr
hv

An allylic radical is more stable (lower in energy) than a tertiary radical.
o Compare bond dissociation energies:
H
H
H = 95 kcal/mol
H
H = 91 kcal/mol
H
H = 87 kcal/mol
H
H
o Electronic explanation:
Resonance!
H
H
R
H
an allylic radical--resonance stabilized
Reaction mechanism (essentially the same as for radical halogenation of alkanes):

If there is more than one kind of allylic hydrogen, multiple products form:

Do not confuse radical allylic bromination with bromination of an alkene!!
NBS or Br 2,
hv
Br
Br
Br2 or NBS
no hv to initiate
radical reaction!
Br
Br
Br
Br
Cool applications of radicals: Vitamin E

Vitamin E is known as an antioxidant because is terminates free radical reactions. These
reactions can have slight to serious negative health effects.

The dangerous radicals are often reactive oxygen species (oxygen radicals) that come
from a variety of sources including:






cigarette smoke
environmental pollutants
radiation
ultraviolet light
certain drugs, pesticides, anesthetics and industrial solvents
ozone
a harmful free
radical
a very weak bond
CH3
H
R
O
H3C
O
CH3
CH3
CH3
CH3
Vitamin E
a very stable radical (effectively terminates the chain reaction)
CH3
CH3
O
O
H3C
O
CH3
CH3
CH3
CH3
H3C
CH3
CH3
CH3
CH3
CH3
O
O
H3C
O
CH3

O
CH3
CH3
CH3
CH3
H3C
O
CH3
CH3
CH3
CH3
The more resonance structures that can be formed, the better the anti-oxidant.
Radical halogenation of an alkene

Non Markovnikov addition of H—Br across an alkene
HBr, hv
or peroxides (ROOR)
Br
mechanism:
RO
RO
OR
initiation
H
RO
Br
Br
RO H
Br
Br
more stable radical is formed
(3o favored over 1o)
Br
H
Br
H
Br
Br
propagation

Do not confuse radical addition of HBr with hydrohalogenation of an alkene!!
HBr, hv
or ROOR
HBr
Br
Br
no hv or ROOR to
initiate radical reaction!
Br
List of reactions for flashcards:
Reaction
Do I have to know the mechanism?
Radical halogenation of an alkane
Yes
Radical allylic bromination
Yes
Radical bromination of an alkene
Yes