1. Alkyl Halides

2. Name the following alkyl halides

4. How are alkyl halides prepared?
From alkanes
Free radical halogenation
From alkenes
Hydrohalogenation
Halogenation
From alcohols

5. Free Radical Chlorination

6. Experimental Evidence Helps to Determine Mechanism
Chlorination does not occur at room temperature in the dark.
The most effective wavelength of light is blue that is strongly absorbed by Cl2 gas.
The light-initiated reaction has a high quantum yield (many molecules of product are formed from each photon of light).

7. Free Radical Species are Constantly Generated Throughout the Reaction Propagation

8. Termination: Reaction of any 2 Radicals

9. Chlorination of Propane

10. Chlorination of Methylpropane

11. 3o Radicals are Easiest to Form

12. Stability of Free Radicals

14. (1) Consider the free radical monochlorination of 2,2,5-trimethylhexane. Draw all of the unique products (Ignore stereoisomers). (2) Consider the free radical monochlorination of 1,4-dimethylcyclohexane. The reaction affords three different products (all C8H15Cl). Draw the three products (Ignore stereoisomers).

15. Conversion of Alkenes into Alkyl Halides

16. Conversion of Alcohols into Alkyl Halides
Reactions with HX, SOCl2, PBr3

17. Conversion of Alcohol into a Leaving Group
Form Tosylate (p-TsCl, pyridine)
Use strong acid (H3O+)
Convert to Alkyl Halide (HX, SOCl2, PBr3)

18. Alcohols to Alkyl Halides

19. What the **** is SN1?
Unimolecular Nucleophilic Substitution

20. Lucas Test

21. Qualitative test for Alcohol Characterization

22. 1o and 2o Alcohols: best to use SOCl2, PBr3, or P/I2

23. Thionyl chloride mechanism

24. How would you prepare the following RX from the appropriate alcohols?

25. 7.25] Draw and name the monochlorination products of the reaction of 2-methylpentane with chlorine gas. Which are chiral?
7.36] How would you prepare the ff cpds, starting from cyclopentene and any other reagents needed?
Chlorocyclopentene
Cyclopentanol
Cyclopentylmagnesium chloride
cyclopentane

26. Reactions of Alkyl Halides
Grignard Reagents

27. What’s special with Grignard reagents?

28. Outline a synthetic scheme from the appropriate alkyl halide

29. Reactions of Alkyl Halides
Substitution and Elimination

30. Substitution, Nucleophilic, Bimolecular – SN2

31. Reaction Profile for SN2 Reaction (Wade)

32. Stereochemistry of SN2 Reaction Inversion of Configuration

33. Proof of Inversion of Configuration at a Chiral Center

34. Acetate Approaches from 180o Behind Leaving Group

35. Inversion on a Ring is often more Obvious: Cis Trans

36. Substrate Reactivity
Since the energy of the transition state is significant in determining the rate of the reaction, a primary substrate will react more rapidly than secondary (which is much more rapid than tertiary).

37. 1o > 2o >> 3o Bulkiness of Substrate

38. Polar, Aprotic Solvents favor SN2

39. Nucleophilicity

40. Iodide vs. Fluoride as Nucleophiles

41. Nucleophiles (preferably non-basic)

42. Good Leaving Groups are Weak Bases

43. Common Leaving Groups

44. SN2 and E2

45. Bimolecular Elimination - E2 Nucleophile acts as Bronsted Base

46. SN2 Competes with E2

47. SN2 Competes with E2

48. SN2 Competes with E2

49. Stereochemistry of E2

50. Anti-Coplanar Conformation

51. 3(R),4(R) 3-Bromo-3,4-dimethylhexane

52. H and Br Anti-coplanar orientation

53. In a Cyclohexane, Leaving Group must be Axial

54. Zaitsev’s Rule

55. More Stable Alkene Predominates

56. Hyperconjugation p bond associates with adjacent C-H s bond

57. With Bulky Base, Hofmann Product Forms

58. Which will react more rapidly?

59. Reactive Conformations

60. E2 Reaction of (R,R) 2-iodo-3-methylpentane

61. Stereochemistry is Important

62. Unimolecular Substitution and Elimination – SN1 and E1

63. SN1 mechanism (Wade) 1st step is rate determining

64. Reaction Profiles (Wade) SN1 SN2

65. SN1 Transition State

66. SN1 Solvent Effects

67. Partial Racemization in SN1

68. Carbocation Stability more highly substituted, lower energy

70. Carbocation Stability

71. Carbocations can Rearrange 1,2-Hydride Shift

72. Hydride shift

73. E1 Mechanism

74. E1 and SN1 Compete

75. Dehydration of Alcohols – E1

77. Draw the Major Product & Predict the Mechanism

91. Which Reacts More Rapidly in E2 Reaction?

92. Cis Reacts more Rapidly

93. What is an E1CB reaction?
Poor LG 2 carbons away from a carbonyl carbon (beta alcohol)
Proceeds via a carbanion intermediate stabilized by resonance.
Step 1: Abstraction of alpha proton
Step 2: Ejection of leaving group.