Transcript Document

Spring 2009
Dr. Halligan
CHM 236
Chapter 15
Radical Reactions
1
Introduction
• A significant group of reactions involve radical
intermediates.
• A radical is a reactive intermediate with a single
unpaired electron, formed by homolysis of a covalent
bond.
• A radical contains an atom that does not have an octet of
electrons.
• Half-headed arrows are used to show the movement of
electrons in radical processes.
2
Introduction
• Carbon radicals are classified as 1°, 2° or 3°.
• A carbon radical is sp2 hybridized and trigonal planar,
like sp2 hybridized carbocations.
• The unhybridized p orbital contains the unpaired
electron and extends above and below the trigonal
planar carbon.
3
Introduction
Figure 15.1
The relative stability of 1°
and 2° carbon radicals
4
General Features of Radical Reactions
• Radicals are formed from covalent bonds by adding
energy in the form of heat () or light (h).
• Some radical reactions are carried out in the presence of
a radical initiator.
• Radical initiators contain an especially weak bond that
serves as a source of radicals.
• Peroxides, compounds having the general structure
RO—OR, are the most commonly used radical initiators.
• Heating a peroxide readily causes homolysis of the weak
O—O bond, forming two RO• radicals.
• Radicals undergo two main types of reactions—they
react with  bonds, and they add to  bonds.
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Reaction of a Radical X• with a C-H Bond.
• A radical X• abstracts a hydrogen atom from a C—H  bond to
from H—X and a carbon radical.
Reaction of a Radical X• with a C=C Bond.
• A radical X• also adds to the  bond of a carbon—carbon double
bond.
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Two Radicals Reacting with Each Other.
• A radical X•, once formed, rapidly reacts with whatever is
available, usually a stable  or  bond.
• Occasionally, two radicals react to form a sigma bond.
• The reaction of a radical with oxygen (a diradical in its ground
state electronic configuration) is another example of two radicals
reacting with each other.
• Compounds that prevent radical reactions from occurring are
called radical inhibitors or radical scavengers. Besides O2,
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vitamin E and other related compounds are radical scavengers.
Chlorination and Bromination of Alkanes
• Alkanes are not very reactive since they only contain
strong s bonds.
• The only two reactions that alkanes undergo are
combustion and halogenation.
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Chlorination and Bromination of Alkanes
• In addition to combustion reactions, alkanes undergo halogenation.
• These reactions take place only with heat (D) or in the presence of
light (hn).
• When subjected to high temperatures or light, Cl-Cl and Br-Br bonds
will cleave homolytically to produce two radicals (initiation step).
• If the goal is to maximize the yield of monohalogenated product,
then an excess of alkane should be used.

a.
CH4
Cl2
+
or
h
CH3Cl
+
HCl
+
HBr

b.
CH3CH3
+
Br2
or
h
Br
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Monochlorination of Alkanes
*Monobromination follows the same mechanism.
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Radical Stability follows the same trend a
Carbocation Stability
• Radicals are stabilized
by hyperconjugation
just like carbocations
and so neighboring
alkyl groups provide
stabilization.
• The stabilization for
radicals derived
through
hyperconjugation is
not as dramatic
because there is an
unpaired electron in
an antibonding MO.
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Factors that Determine Product Distribution
• When more than one proton is available for abstraction, there will be
a distribution of products.
• The ratio of halogenated products depends on both probability
(number of available hydrogens for abstraction) and the stability of
the alkyl radical formed during the rate determining hydrogen
abstraction step.
• Radical stability follows the same order as carbocation stability.
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Monochlorination of Butane
• Consider the monochlorination of butane.
• Experimentally, it is observed that 1-chlorobutane is produced
in 29% and 2-chlorobutane is formed in 71% yield.
• How can we predict this distribution?
• Let’s calculate the product distribution based on probability
and reactivity.
+
Cl2
h
Cl
+
expected = 40%
experimental = 71%
Cl
expected = 60%
experimental = 29%
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Bromine is much more selective
+
Br2
h
Br
+
expected = 40%
experimental = 98%
Br
expected = 60%
experimental = 2%
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Why is bromine much more selective?
• By comparing the DH values for chlorination and
bromination, we see that bromination is a slower process
and requires more energy.
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Why is bromine much more selective?
• These reaction coordinate diagrams help explain why
radical bromination reactions are more selective. See if
you can explain it.
16
Radical fluorination and iodination are
not synthetically useful reactions.
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Factors that Determine Product Distribution
• When more than one proton is available for abstraction, there will be
a distribution of products.
• The ratio of halogenated products depends on both probability
(number of available hydrogens for abstraction) and the stability of
the alkyl radical formed during the rate determining hydrogen
abstraction step.
• Radical stability follows the same order as carbocation stability.
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The Ozone Layer and CFCs
• Ozone is vital to life, and acts as a shield, protecting the earth’s
surface from harmful UV radiation.
• Current research suggests that chlorofluorocarbons (CFCs) are
responsible for destroying ozone in the upper atmosphere.
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The Ozone Layer and CFCs
• CFCs are inert, odorless, and nontoxic, and have been used as
refrigerants, solvents, and aerosol propellants.
• They are water insoluble and volatile, and readily escape into the
upper atmosphere, where they are decomposed by high-energy
sunlight to form radicals that destroy ozone by a radical chain
mechanism.
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The Ozone Layer and CFCs
• The overall result is that O3 is consumed as a reactant and O2 is
formed.
• In this way, a small amount of CFC can destroy a large amount of
O3.
• New alternatives to CFCs are hydrochlorofluorocarbons (HCFCs)
and hydrofluorocarbons (HFCs) such as CH2FCF3.
• These compounds are decomposed by HO• before they reach the
stratosphere and therefore they do not take part in the radical
reactions resulting in O3 destruction.
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The Ozone Layer and CFCs
Figure 15.7
CFCs and the
destruction
of the ozone layer
22
Radical addition of HBr
• If HBr is added in the presence of a peroxide, the reaction proceeds
in an anti-Markovnikov fashion.
• Take a look at the mechanism for an explanation for these results.
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Radical addition of HBr
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Radical addition of HBr
• During propagation, the reaction continues because
there is a radical present.
• The reaction stops when the radicals are converted to
stabled, paired electron species.
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The Peroxide Effect
•
The Peroxide effect is only observed for reactions with HBr and
peroxides, not with any of the other hydrogen halides and peroxides.
•
Both propagation steps are exothermic for the reaction of HBr/peroxides
with an alkene.
26
Stereochemistry of Radical Substitution
and Addition Reactions
• In the following radical substitution reaction, a new
asymmetric center is formed and thus gives rise to a pair of
enantiomers.
• Why are these two compounds a pair of enantiomers and not
a pair of diastereomers?
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Stereochemistry of Radical
Substitution and Addition Reactions
• In the following radical addition reaction of an alkene with
HBr/peroxides, a new asymmetric center is generated.
• Again, a racemic mixture is formed since there is only one
chiral carbon in the product.
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How Do We Explain the Stereochemistry
of Radical Reactions?
• A radical intermediate is similar to a carbocation in terms of
geometry; it is planar (flat).
• So, the next atom that attaches to the radical may approach from
the front side or the back side, leading to two stereoisomers.
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Radical Halogenation at an Allylic Carbon
• An allylic carbon is a carbon adjacent to a double bond.
• Homolysis of the allylic C—H bond in propene generates an
allylic radical which has an unpaired electron on the carbon
adjacent to the double bond.
• The bond dissociation energy for this process is even less than
that for a 30 C—H bond (91 kcal/mol).
• This means that an allyl radical is more stable than a 30 radical.
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Radical Halogenation at an Allylic Carbon
• The allyl radical is more stable than other radicals
because two resonance forms can be drawn for it.
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Radical Halogenation at an Allylic Carbon
• Because allylic C—H bonds are weaker than other sp3 hybridized
C—H bonds, the allylic carbon can be selectively halogenated
using NBS in the presence of light or peroxides.
• NBS contains a weak N—Br bond that is homolytically cleaved
with light to generate a bromine radical, initiating an allylic
halogenation reaction.
• Propagation then consists of the usual two steps of radical
halogenation.
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Radical Halogenation at an Allylic Carbon
33
Radical Halogenation at an Allylic Carbon
• NBS also generates a low concentration of Br2 needed in
the second chain propagation step (Step [3] of the
mechanism).
• The HBr formed in Step [2] reacts with NBS to form Br2,
which is then used for halogenation in Step [3] of the
mechanism.
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Radical Halogenation at an Allylic Carbon
Thus, an alkene with allylic C—H bonds undergoes two
different reactions depending on the reaction conditions.
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Radical Halogenation at an Allylic Carbon
Question:
Why does a low concentration of Br2 (from NBS) favor allylic
substitution (over ionic addition to form the dibromide)?
Answer:
• The key to getting substitution is to have a low concentration of
bromine (Br2).
• The Br2 produced from NBS is present in very low
concentrations.
• A low concentration of Br2 would first react with the double bond
to form a low concentration of the bridged bromonium ion.
• The bridged bromonium ion must then react with more bromine
(in the form of Br¯) in a second step to form the dibromide.
• If concentrations of both intermediates—the bromonium ion and
Br¯ are low (as is the case here), the overall rate of addition is
very slow, and the products of the very fast and facile radical
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chain reaction predominate.
Radical Halogenation at an Allylic Carbon
• Halogenation at an allylic carbon often results in a mixture of
products. Consider the following example:
• A mixture results because the reaction proceeds by way of a
resonance stabilized radical.
37
Radical Halogenation at an Allylic Carbon
• Oils are susceptible to allylic free radical oxidation.
Figure 15.8
The oxidation of unsaturated
lipids with O2
38
Antioxidants
• An antioxidant is a compound that stops an oxidation from
occurring.
• Naturally occurring antioxidants such as vitamin E prevent
radical reactions that can cause cell damage.
• Synthetic antioxidants such as BHT—butylated hydroxy
toluene—are added to packaged and prepared foods to prevent
oxidation and spoilage.
• Vitamin E and BHT are radical inhibitors, so they terminate
radical chain mechanisms by reacting with the radical.
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Antioxidants
• To trap free radicals, both vitamin E and BHT use a hydroxy
group bonded to a benzene ring—a general structure called a
phenol.
• Radicals (R•) abstract a hydrogen atom from the OH group of an
antioxidant, forming a new resonance-stabilized radical. This new
radical does not participate in chain propagation, but rather
terminates the chain and halts the oxidation process.
• Because oxidative damage to lipids in cells is thought to play a
role in the aging process, many anti-aging formulations contain
antioxidants.
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Polymers and Polymerization
• Polymers are large molecules made up of repeating units of
smaller molecules called monomers. They include biologically
important compounds such as proteins and carbohydrates, as
well as synthetic plastics such as polyethylene, polyvinyl
chloride (PVC) and polystyrene.
• Polymerization is the joining together of monomers to make
polymers. For example, joining ethylene monomers together
forms the polymer polyethylene, a plastic used in milk containers
and plastic bags.
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Polymers and Polymerization
• Many ethylene derivatives having the general structure
CH2=CHZ are also used as monomers for polymerization.
• The identity of Z affects the physical properties of the
resulting polymer.
• Polymerization of CH2=CHZ usually affords polymers
with Z groups on every other carbon atom in the chain.
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Polymers and Polymerization
43
Polymers and Polymerization
44
Polymers and Polymerization
• In radical polymerization, the more substituted radical
always adds to the less substituted end of the monomer,
a process called head-to-tail polymerization.
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