1. Chapter 12 Organic Chemistry 6th Edition Radicals Reactions of Alkanes
Paula Yurkanis Bruice
Chapter 12
Radicals
Reactions of Alkanes

2. Petroleum is a complex mixture of alkanes and
cycloalkanes that can be separated by distillation:

3. Alkanes are very unreactive compounds because
they have only strong s bonds and atoms with no partial charges
However, alkanes do react with Cl2 and Br2:

7. Consider the relative stabilities of alkyl radicals:
Alkyl groups stabilize carbocations about 5–10 times better than they stabilize radicals:
Radicals: Resonance > Hyperconjugation
Carbocations: Hyperconjugation > Resonance

8. Why does hyperconjugation stabilize carbocations more than radicals?
One of the
electrons is
in the antibonding
orbital
Carbocation:
Both electrons
are in the bonding
orbital

9. However, secondary hydrogens are more reactive than primary hydrogens
The Distribution of Products Depends on
Probability and Reactivity
Probability is based on relative number of primary and secondary protons, 6:4
However, secondary hydrogens are more reactive than primary hydrogens
Therefore, probability and reactivity both contribute to product distribution

11. To determine the the product distribution, consider both probability and reactivity:
Probability: the number of hydrogens that can be abstracted that will lead to the formation of the particular product
Reactivity: the relative rate at which a particular hydrogen is abstracted

12. An example of calculating the distribution of radical chlorination products:

13. The Reactivity–Selectivity Principle
Radical bromination is more selective than radical chlorination:

14. Reactivity–Selectivity Principle
Monochlorination reactions:
Monobromination reactions:

15. Radical stability important Radical stability not important
Why is the bromine radical more selective than the chlorine radical?
Radical stability important
Radical stability not important
Hammond postulate:
Endothermic, a product-like (radical) transition state
Exothermic, a reactant-like (alkane) transition state
Therefore, the bromine atom more readily distinguishes 3º, 2º, and 1º hydrogens

16. The more reactive a species is, the less selective it will
be:

17. What about fluorination and iodination?
Alkanes undergo chlorination and bromination, but not iodination
Fluorination is too violent a reaction to be useful:

18. Addition of Radicals to an Alkene
Peroxide is used to generate Br radical in trace quantities

19. An alkyl peroxide is a radical initiator
The electrophile adds to the sp2 carbon that is bonded to
the greater number of hydrogens

21. Radicals do not rearrange as readily as carbocations:

22. Why is the peroxide effect observed only for the addition
of HBr to alkene?
Because both of the propagation steps in the HBr addition reaction are exothermic.

23. Stereochemistry of Radical Substitution Reactions

24. Stereochemistry of Radical Addition Reactions

25. Why are both enantiomers formed?
Consider the first propagation step:

26. Radical Substitution of Benzylic and Allylic Hydrogens
The more stable radicals form faster:

27. The percentage of substitution at the benzylic or allylic
carbon is greater for bromination. Note the reactivity–selectivity principle:

28. No Br2 addition to the alkene
Because of the presence of an alkene functional group, N-bromosuccinimide is used as a brominating agent for allylic compounds:
No Br2 addition to the alkene

29. Mechanism of NBS Bromination
Azobisisobutylnitrile
radical initiator

30. Advantage: The low concentrations of Br2 and HBr present during NBS bromations result in no alkene addition reactions:

31. Designing a Multistep Synthesis
Example 1
Synthesis:

32. Example 2
Racemic
Racemic
Synthesis:

33. Retosynthetic analysis:
Example 3
Retosynthetic analysis:
Synthesis:

34. Radical Reactions in Biological Systems
Cytochrome-mediated hydroxylation of an alkane:
Conversion of nicotine to a polar metabolite:

35. The Heme Cofactor of a Cytochrome
The FeII is converted to the reactive FeV oxide

36. Antihistamine Metabolism: Allegra
Cytochrome oxidation
Site of oxidation depends on accessibility rather than radical stability

37. Other Reactions of Radicals
Reaction of ethers to form highly explosive peroxides:
Reactive Oxygen Species:
Caution: Ethers may have dangerous levels of peroxides!

38. Reactive Oxygen Species (ROS) Are Common in Biological Systems
Oxidation of an unsaturated fat:
Terminating the radical chain reaction with a phenolic compound:
Radical is resonance stabilized and not propagated

39. Radical Chain Terminators: Antioxidants
Fat-soluble
Water-soluble

40. Commonly Used Antioxidant Preservatives
BHT is used in packaging:
A radical that cannot propagate:
Resonance stabilized
Sterically hindered
Hydroquinone is used to preserve ethers:

41. Naturally Occurring Antioxidants
Rutin is a bioflavonoid glycoside with antioxidant and anticancer properties:
Bioflavonoids afford resonance-stabilized radicals:
Stars show the resonance delocation of the radical
Found in citrus fruit and berries

42. Green Tea Antioxidants
Note the abundance of phenolic hydroxyls:

43. Green Tea Antioxidants
Formed from catechins
during tea fermentation

44. Radicals and Stratospheric Ozone
Ozone is a major constituent of smog
Ozone shields Earth from harmful radiation

45. Chlorofluorocarbons remain very stable in the
atmosphere until they reach the stratosphere:
The chlorine radicals are ozone-removing agents: