Free Radical Reactions Halogenation of Alkanes

1. Free Radical ReactionsHalogenation of Alkanes RH + X2 RX + HX

2. Reactive Intermediates • Orbital hybridization in carbocations and carbanions:

3. Reactive Intermediates:Free Radicals • Free radicals can be thought of as sp2 hybridized or quickly interconverting sp3 hybridized.

4. Energetics • RH + X2 RX + HX • explosive for F2 • exothermic for Cl2 and Br2 • endothermic for I2

5. HalogenationThermodynamics

6. Chlorination of Methane

7. Chlorination of Methane • carried out at high temperature (400 °C) • CH4 + Cl2  CH3Cl + HCl • CH3Cl + Cl2  CH2Cl2 + HCl • CH2Cl2 + Cl2  CHCl3 + HCl • CHCl3 + Cl2  CCl4 + HCl

8. Mechanism of Chlorination of Methane

9. .. .. .. .. . . : : : : : Cl Cl Cl Cl .. .. .. .. Mechanism of Chlorination of Methane Free-radical chain mechanism. • The initiation step "gets the reaction going"by producing free radicals—chlorine atomsfrom chlorine molecules in this case. • Initiation step is followed by propagationsteps. Each propagation step consumes onefree radical but generates another one. Initiation step: (Light or Heat is Necessary) +

10. Question • Which of the above initiates reactions most readily? A) B) C)

11. .. .. . . H3C H : Cl: Cl: .. .. Second propagation step: .. .. .. .. . . + : : : : : Cl: + Cl Cl Cl H3C H3C .. .. .. .. Mechanism of Chlorination of Methane First propagation step: + H3C : H +

12. .. .. . . H3C H : Cl: Cl: .. .. .. .. .. .. . . : : : : : Cl: Cl Cl Cl H3C H3C .. .. .. .. .. .. .. .. : : Cl : : : H3C H : Cl: Cl Cl .. .. .. .. Mechanism of Chlorination of Methane First propagation step: + H3C : H + Second propagation step: + + + + H3C : H

13. .. .. . . H3C H : Cl: Cl: .. .. .. .. .. .. . . : : : : : Cl: Cl Cl Cl H3C H3C .. .. .. .. .. .. .. .. : : Cl : : : H3C H : Cl: Cl Cl .. .. .. .. Almost all of the product is formed by repetitivecycles of the two propagation steps. First propagation step: + H3C : H + Second propagation step: + + + + H3C : H

14. .. .. . . : : Cl H3C H3C Cl: .. .. Termination Steps • stop chain reaction by consuming free radicals • hardly any product is formed by termination stepbecause concentration of free radicals at anyinstant is extremely low +

15. Question • The step shown below is a _____________ step of the free-radical chlorination of • chloromethane. • A)initiation • B)propagation • C)chain-terminating • D)bond cleavage

16. Question • For the free-radical reaction below, light is involved in which of the following reaction • steps? • A)Initiation only • B)Propagation only • C)Termination only • D)Initiation and propagation

17. Halogenation of Higher Alkanes

18. Chlorination of Alkanes • can be used to prepare alkyl chlorides from alkanes in which all of the hydrogens are equivalent to one another 420°C CH3CH3 + Cl2 CH3CH2Cl + HCl (78%) h + Cl2 + HCl Cl (73%)

19. Chlorination of Alkanes Major limitation: Chlorination gives every possible monochloride derived from original carbonskeleton. Not much difference in reactivity ofdifferent hydrogens in molecule.

20. Example • Chlorination of butane gives a mixture of1-chlorobutane and 2-chlorobutane. (28%) CH3CH2CH2CH2Cl Cl2 CH3CH2CH2CH3 h CH3CHCH2CH3 (72%) Cl

21. 10% 10% 10% 10% 10% 10% 10% 10% 10% 10% Percentage of Product that Results from Substitution of Indicated Hydrogen if Every Collision with Chlorine Atoms is Productive

22. Percentage of Product that Actually Results from Replacement of Indicated Hydrogen 18% 18% 4.6% 4.6% 4.6% 4.6% 4.6% 4.6% 18% 18%

23. 4.6 4.6 18 4.6 Relative Rates of Hydrogen Atom Abstraction 18% 4.6% • divide by 4.6 = 1 = 3.9 A secondary hydrogen is abstracted 3.9 times faster than a primary hydrogen by a chlorine atom.

24. CH3 (63%) CH3CCH2Cl CH3 H Cl2 CH3CCH3 h H CH3 CH3CCH3 (37%) Cl • Similarly, chlorination of 2-methylbutane gives a mixture of isobutyl chloride and tert-butyl chloride

25. Question • How many monochlorination products do you expect to obtain from the chlorination of • 2-methylbutane? • A)two • B)three • C)four • D)five

26. Percentage of Product that Results from Replacement of Indicated Hydrogen 7.0% 37%

27. Relative Rates of Hydrogen Atom Abstraction • divide by 7 7.0 37 = 5.3 = 1 7 7 A tertiary hydrogen is abstracted 5.3 times faster than a primary hydrogen by a chlorine atom.

28. Radicals - Resonance ?

29. QuestionTrue (A) / False (B) • Hyperconjugationcontributes more to thermodynamic stability than resonance.

30. QuestionTrue (A) / False (B) • Vinyl free radicals are more thermodynamically stable thanbenzylic and allylic free radicals.

31. Selectivity of Free-radical Halogenation • R3CH > R2CH2 > RCH3 • chlorination: 5 4 1 • bromination: 1640 82 1 • Chlorination of an alkane gives a mixture of every possible isomer having the same skeletonas the starting alkane. Useful for synthesis only when all hydrogens in a molecule are equivalent. Bromination is highly regioselective for substitution of tertiary hydrogens. Major synthetic application is in synthesis of tertiary alkyl bromides.

32. Radicals - Bromination

33. Question • How many mono-bromination products are expected from the following reaction? • A. 5 B. 4 C. 3 D. 2 E. 1

34. Cl Cl2 h Synthetic Application of Chlorination of an Alkane • Chlorination is useful for synthesis only when all of the hydrogens in a molecule are equivalent. (64%)

35. Question • An alkane with a molecular formula of C8H18 reacts with Cl2 in the presence of light and • heat to give a single monochloride C8H17Cl. What is the most reasonable structure for the starting alkane? • A) CH3CH2CH2CH2CH2CH2CH2CH3 • B) (CH3CH2)2CHCH2CH2CH3 • C) (CH3)2CHCH2CH2CH(CH3)2 • D) (CH3)3CC(CH3)3

36. Br H CH3CCH2CH2CH3 CH3CCH2CH2CH3 CH3 CH3 Synthetic Application of Bromination of an Alkane Br2 • Bromination is highly selective for substitution of tertiary hydrogens. • Major synthetic application is in synthesis of tertiary alkyl bromides. h (76%)

37. Question • Which of the following best describes a mechanistic feature of the free-radical bromination (Br2, light) of 2-methylpropane? • A) The initiation step involves cleavage of a C-H bond. • B) The free-radical (CH3)3C· is produced in one propagation step and reacts with Br2 in another. • C) The reaction is characterized by the homolytic cleavage of the C-Br bond. • D) The reaction is concerted; i.e., it occurs in a single step.

38. Question • Which reaction has a faster rate? • Which product is kinetically favored? • A. I) and I) B. II) and II) C. I) and II) D. II) and I) I) II)

39. Question • Which reaction has a propagation step that is endothermic?Which reaction is more regioselective? • A. I) and I) B. II) and II) C. I) and II) D. II) and I) I) II)

40. Stereochemistry • Three mono-substituted isomers form in the halogenation of butane. The products are optically inactive.

41. Question • True (A) / False (B) • Bromination of optically active 3-methylhexane produces only (S)-3-bromo-3-methylhexane.

42. Question • How many products (including stereoisomers) are expected in the following halogenation? • A. 5 B. 4 C. 3 D. 2 E. 1

43. Allylic/BenzylicBromination • Resonance and regioselectivity: Br- A mixture is obtained that includes the di-brominated product. Di-bromination can be avoided using a specialized reagent: N-bromosuccinimide (NBS)

44. Allylic/BenzylicBromination • N-bromosuccinimide (NBS)

45. Question What is the major product of the following reaction?

46. Halogenated Marine Natural Products (A) Barbamide, a cyanobacterial peptide containing a trichloromethyl group and (B) dysidenin, a barbamide-related compound isolated from a sponge-cyanobacterial association

47. Polymers

48. Radical Polymerization • Free radical conditions are frequently used to form polymers. • Recall that a polymerization process joins together many small units called monomers in a long chain.

49. Radical Polymerization • Radical polymerizations commonly proceed through a chain reaction mechanism.

50. Radical Polymerization