1. Radical Reactions

2. Free Radicals
Free radicals form when bonds break homolytically
Note the single-barbed or fishhook arrow used to show the electron movement

3. Free Radicals
Recall the orbital hybridization in carbocations and carbanions

4. Free Radicals
Free radicals can be thought of as sp2 hybridized or quickly interconverting sp3 hybridized
sp2 hybridized

5. 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 via hyperconjugation.

6. Free Radical Resonance
When drawing resonance for free radicals, use fishhook arrows to show electron movement
An allylic radical is stabilized by resonance

7. Free Radical Resonance
The benzylic radical is a hybrid that consists of 4 contributors
Hybrid δ δ δ δ

8. Resonance Stabilization
How does resonance affect the stability of a radical? WHY?

9. Resonance Stabilization
Vinylic free radicals are especially unstable
The vinylic free radical is located in an sp2 orbital, and cannot be stabilized by resonance.

10. 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

11. 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

12. 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)
Coupling: the reverse of homolytic cleavage
Note that radical electron movement generally involves 2 or 3 fishhook arrows

13. Radical Electron Movement
Note the reversibility of radical processes

14. 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

15. Radical Electron Movement
Propagation occurs when radicals are moved from one location to another
Propagation

16. 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

17. Chlorination of Methane

18. Chlorination of Methane
Why do termination reactions happen less often than propagation reactions?

19. Chlorination of Methane
The propagation steps give the net reaction
Initiation produces a small amount Cl• radical
H abstraction consumes the Cl• radical
Cl abstraction generates a Cl• radical, which can go on to start another H abstraction
Propagation steps are self-sustaining

20. Chlorination of Methane
Reactions that have self-sustaining propagation steps are called chain reactions
Chain reaction: the products from one step are reactants for a different step in the mechanism
Polychlorination is difficult to prevent, especially when an excess of Cl2 is present.

21. 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?

22. Radical Inhibitors
Inhibitors act in a reaction to scavenge free radicals to stop chain reaction processes
Oxygen molecules can exist in the form of a diradical, which reacts readily with other radicals. Use arrows to show the process

23. Radical Inhibitors
Hydroquinone is also often used as a radical inhibitor
Draw in necessary arrows in the reactions above

24. Halogenation Thermodynamics
If we want to determine whether a process is product favored, we must determine the sign (+/-) for ΔG
In a halogenation reaction, will ΔH or -TΔS have a bigger effect on the sign of ΔG? WHY?

25. Halogenation Thermodynamics
Because the -TΔS term should be close to zero, we can simplify the free energy equation
Considering the bonds that break and form in the reaction, estimate ΔHhalogenation for each of the halogens in the table below

26. Halogenation Thermodynamics

27. Halogenation Thermodynamics
Fluorination is so exothermic that it is impractical.
Iodination is nonspontaneous, so it is not product favored

28. Halogenation Thermodynamics
Consider chlorination and bromination in more detail
Chlorination is more product favored than bromination

29. Halogenation Thermodynamics
Which step in the mechanism is the slow step? Which reaction has a faster rate? Which is more product favored?
First step is endothermic
Both steps are exothermic
Second step is exothermic

30. Halogenation Regioselectivity
With substrates more complex than ethane, multiple monohalogenation products are possible
If the halogen were indiscriminant, predict the product ratio?

31. Halogenation Regioselectivity
For the CHLORINATION process, the actual product distribution favors 2-chloropropane over 1-chloropropane
Which step in the mechanism determines the regioselectivity?
Show the arrow pushing for that key mechanistic step

32. Chlorination Energy Diagram
Lower Ea, faster rate, so more stable intermediate is formed faster.

33. Halogenation Regioselectivity
For the BROMINATION process, the product distribution vastly favors 2-bromopropane over 1-bromopropane
Which step in the mechanism determines regioselectivity?
Show the arrow pushing for that key mechanistic step

34. Chlorination Vs. Bromination

35. Endothermic and Exothermic Diagrams

36. Halogenation Regioselectivity
Which process is more regioselective? WHY?

37. Halogenation Regioselectivity
Bromination at the 3° position happens 1600 times more often than at the 1° position

38. Halogenation Regioselectivity
Free-radical bromination is highly selective, chlorination is moderately selective, and fluorination is nearly nonselective.

39. Halogenation Stereochemistry
The halogenation of butane or more complex alkanes forms a new chirality center
2-chlorobutane will form as a racemic mixture
Which step in the mechanism is responsible for the stereochemical outcome?

40. Halogenation Stereochemistry
Three monosubstituted products form in the halogenation of butane because halogen abstraction will occur on either side of the plane with equal probability

41. Halogenation Stereochemistry
In the halogenation of (S)-3-methylhexane, the chirality center is the most reactive carbon in the molecule.

42. Halogenation Stereochemistry
Draw all of the monosubstituted products that would form in the halogenation below including all stereoisomers

43. Allylic Halogenation
When an C=C double bond is present it affects the regioselectivity of the halogenation reaction
Given the bond dissociation energies below, which position of cyclohexene will be most reactive toward halogenation?

44. 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
What other set of side-products is likely to form in this reaction?

45. Allylic Halogenation with NBS
To avoid the competing halogenation addition reaction, NBS can be used to supply Br• radicals
Heat or light initiates the process

46. 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

47. Allylic Halogenation with NBS
Give a mechanism that explains the following product distribution. Hint: resonance

48. Atmospheric Chemistry and O3
Ozone is both created and destroyed in the upper atmosphere
O3 molecules absorb harmful UV radiation
O3 molecules are recycled as heat energy is released

49. Atmospheric Chemistry and O3
For this process to be spontaneous, the entropy of the universe must increase
Heat is a more disordered form of energy than light. WHY?

50. Atmospheric Chemistry and O3
O3 depletion (about 6% each year) remains a serious health and environmental issue
Compounds that are most destructive to the ozone layer
Are stable enough to reach the upper atmosphere
Form free radicals that interfere with the O3 recycling process
Chlorofluorocarbons (CFCs) fit both criteria
Atmosphere O3 is vital for protection, but what effect does O3 have at the earth’s surface?

51. Atmospheric Chemistry and O3
CFC substitutes that generally decompose before reaching the O3 layer include hydrochlorofluorocarbons
Hydrofluorocarbons don’t even form the chlorine radicals that interfere with the O3 cycle

52. Combustion and Firefighting
Like most reactions, combustion involves breaking bonds and forming new bonds
A fuel is heated with the necessary Eact to break bonds (C-C, C-H, and O=O) homolytically
The resulting free radicals join together to form new O-H and C=O bonds
Why does the process release energy overall?
What types of chemicals might be used in fire extinguishers to inhibit the process?

53. Combustion and Firefighting
Water deprives the fire of the Eact needed by absorbing the energy
CO2 and Argon gas deprive the fire of needed oxygen
Halons are very effective fire-suppression agents
Halons suppress combustion in three main ways

54. Combustion and Firefighting
Halons suppress combustion in three main ways
As a gas, they can smother the fire and deprive it of O2
They absorb some of the Eact for the fire by undergoing homolytic cleavage
The free radicals produced can combine with C• and H• free radicals to terminate the combustion chain reaction

55. Combustion and Firefighting
How do you think the use of halons to fight fires affects the ozone layer?
FM-200 is an alternative firefighting agent
Practice with conceptual checkpoint 11.18