Organic Chemistry
Second Edition
David Klein
Chapter 11
Radical Reactions
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Klein, Organic Chemistry 2e
11.1 Free Radicals
• Free radicals form when bonds break homolytically
• Note the single-barbed or fishhook arrow used to show
the electron movement
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Klein, Organic Chemistry 2e
11.1 Free Radicals
• Recall the orbital hybridization in carbocations and
carbanions
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11-3
Klein, Organic Chemistry 2e
11.1 Free Radicals
• Free radicals can be thought of as sp2 hybridized or
quickly interconverting sp3 hybridized
sp2 hybridized
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11-4
Klein, Organic Chemistry 2e
11.1 Free Radical Stability
• Free radicals do not have a formal charge but are
unstable because of an incomplete octet
• Groups that can push (donate) electrons toward the free
radical will help to stabilize it. WHY? HOW? Consider
hyperconjugation
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11-5
Klein, Organic Chemistry 2e
11.1 Free Radical Resonance
• Drawing resonance for free radicals using fishhook
arrows to show electron movement
• Remember, for resonance, the arrows don’t ACTUALLY
show electron movement. WHY?
• Draw the resonance hybrid for an allyl radical
• HOW and WHY does resonance affect the stability of the
free radical?
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Klein, Organic Chemistry 2e
11.1 Free Radical Resonance
• The benzylic radical is a hybrid that consists of 4
contributors
• Draw the remaining contributors
• Draw the hybrid
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Klein, Organic Chemistry 2e
11.2 Radical Electron Movement
• Free radical electron movement is quite different from
electron movement in ionic reactions
• For example, free radicals don’t undergo rearrangement
• There are SIX key arrow-pushing patterns that we will
discuss
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11-8
Klein, Organic Chemistry 2e
11.2 Radical Electron Movement
1. Homolytic Cleavage: initiated by light or heat
2. Addition to a pi bond
3. Hydrogen abstraction: NOT the same as proton transfer
4. Halogen abstraction
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Klein, Organic Chemistry 2e
11.2 Radical Electron Movement
5. Elimination: the radical from the α carbon is pushed
toward the β carbon to eliminate a group on the β
carbon (reverse of addition to a pi bond)
–
The –X group is NOT a leaving group. WHY?
6. Coupling: the reverse of homolytic cleavage
•
Note that radical electron movement generally involves
2 or 3 fishhook arrows
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11-10
Klein, Organic Chemistry 2e
11.2 Radical Electron Movement
•
Note the reversibility of radical processes
•
Practice with SkillBuilder 11.3
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11-11
Klein, Organic Chemistry 2e
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e
11.2 Radical Electron Movement
•
Radical electron movement is generally classified as
either initiation, termination, or propagation
Initiation
Termination
• Termination
occurs when
radicals are
destroyed
• Initiation
occurs
when
radicals are
created
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Klein, Organic Chemistry 2e
11.2 Radical Electron Movement
• Propagation occurs when radicals are moved from one
location to another
Propagation
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Klein, Organic Chemistry 2e
11.3 Chlorination of Methane
• Let’s apply our electron-pushing skills to a reaction
• We must consider each pattern for any free radical that
forms during the reaction
• Is homolytic cleavage also likely for CH4?
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Klein, Organic Chemistry 2e
11.3 Chlorination of Methane
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Klein, Organic Chemistry 2e
11.3 Chlorination of Methane
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Klein, Organic Chemistry 2e
11.3 Chlorination of Methane
• Draw a reasonable mechanism that shows how each of
the products might form in the following reaction
• Which of the products above are major and which are
minor? Are other products also possible?
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Klein, Organic Chemistry 2e
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e
11.7 Allylic Halogenation
• When an allylic hydrogen is abstracted, it leaves behind
an allylic free radical that is stabilized by resonance
• Based on the high selectivity of bromination that we
discussed, you might expect bromination to occur as
shown below
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11-20
Klein, Organic Chemistry 2e
11.7 Allylic Halogenation with NBS
• To avoid the competing halogenation addition reaction,
NBS can be used to supply Br• radicals
• Show how resonance stabilizes the succinimide radical
• Heat or light initiates the process
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11-21
Klein, Organic Chemistry 2e
11.7 Allylic Halogenation with NBS
• Propagation produces new Br• radicals to continue the
chain reaction
• Where does the Br-Br above come from? The amount of
Br-Br in solution is minimal, so the competing addition
reaction is minimized
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11-22
Klein, Organic Chemistry 2e
11.7 Allylic Halogenation with NBS
• The succinimide radical that is produced in the initiation
step can also undergo propagation when it collides with
an H-Br molecule. Show a mechanism
+ H-Br
• Give some examples of some termination steps that
might occur
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11-23
Klein, Organic Chemistry 2e
11.7 Allylic Halogenation with NBS
• Give a mechanism that explains the following product
distribution. Hint: resonance
• Practice with SkillBuilder 11.7
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11-24
Klein, Organic Chemistry 2e
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e
11.10 Anti-Markovnikov Addition
• We learned in chapter 9 that H-X will add across a C=C
double bond with anti-Markovnikov regioselectivity
when peroxides are present
• Now that we have discussed free radicals, we can
explain the mechanism for the anti-Markovnikov
addition
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Klein, Organic Chemistry 2e
11.10 Anti-Markovnikov Addition
• The O-O single bond can break homolytically with a
relatively low Eact
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Klein, Organic Chemistry 2e
11.10 Anti-Markovnikov Addition
• The Br• radical reacts to give the more stable C• radical
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Klein, Organic Chemistry 2e
11.10 Addition Stereochemistry
• Addition reactions often form a new chirality center
• Recall that at least 1 reagent in the reaction must be
chiral for the reaction to be stereoselective
• Predicts the product distribution for the reaction below
and explain the stereochemical outcome
• Practice with SkillBuilder 11.8
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11-29
Klein, Organic Chemistry 2e
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e
11.13 Synthetic Utility of Halogenation
• Radical chlorination and bromination are both useful
processes
• Recall that bromination is more selective. WHY?
• Temperature can be used to help avoid polysubstitution.
HOW?
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Klein, Organic Chemistry 2e
11.13 Synthetic Utility of Halogenation
• Chlorination can be useful with highly symmetrical
substrates
• It is difficult to avoid polysubstitution. WHY?
• The synthetic utility of halogenation is limited
– Chlorination is difficult to control
– Bromination requires a substrate with 1 site that is
significantly more reactive than all others
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Klein, Organic Chemistry 2e
11.13 Synthetic Utility of Halogenation
• Synthesizing a target molecule from an alkane is
challenging because of its limited reactivity
• Often halogenation is the best option
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Klein, Organic Chemistry 2e