1. Organic Chemistry Second Edition Chapter 11 David Klein
Radical Reactions
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Klein, Organic Chemistry 2e

2. 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

3. 11.1 Free Radicals
Recall the orbital hybridization in carbocations and carbanions
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Klein, Organic Chemistry 2e

4. 11.1 Free Radicals
Free radicals can be thought of as sp2 hybridized or quickly interconverting sp3 hybridized
sp2 hybridized
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Klein, Organic Chemistry 2e

5. 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
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

6. 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?
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

7. 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

8. 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
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

9. 11.2 Radical Electron Movement
Homolytic Cleavage: initiated by light or heat
Addition to a pi bond
Hydrogen abstraction: NOT the same as proton transfer
Halogen abstraction
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

10. 11.2 Radical Electron Movement
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?
Coupling: the reverse of homolytic cleavage
Note that radical electron movement generally involves 2 or 3 fishhook arrows
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

11. 11.2 Radical Electron Movement
Note the reversibility of radical processes
Practice with SkillBuilder 11.3
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

12. Klein, Organic Chemistry 2e
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

13. 11.2 Radical Electron Movement
Radical electron movement is generally classified as either initiation, termination, or propagation
Initiation
Termination
Initiation occurs when radicals are created
Termination occurs when radicals are destroyed
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

14. 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

15. 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?
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

16. 11.3 Chlorination of Methane
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Klein, Organic Chemistry 2e

17. 11.3 Chlorination of Methane
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Klein, Organic Chemistry 2e

18. 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

19. Klein, Organic Chemistry 2e
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

20. 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
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

21. 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
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

22. 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
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

23. 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
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

24. 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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Klein, Organic Chemistry 2e

25. Klein, Organic Chemistry 2e
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

26. 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
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

27. 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

28. 11.10 Anti-Markovnikov Addition
The Br• radical reacts to give the more stable C• radical
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Klein, Organic Chemistry 2e

29. 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
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

30. Klein, Organic Chemistry 2e
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

31. 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?
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

32. 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
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

33. 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
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e