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16.10 Conversion of Vicinal Halohydrins to Epoxides

16.10 Conversion of Vicinal Halohydrins to Epoxides. Dr. Wolf's CHM 201 & 202. 16-51. H. O H. H. Br. Example. H. NaOH. O. H 2 O. H. (81%). Dr. Wolf's CHM 201 & 202. 16-52. H. O H. H. Br. Example. H. NaOH. O. H 2 O. H. (81%). ••. –. O. via:. • •. • •. H. H. Br.

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16.10 Conversion of Vicinal Halohydrins to Epoxides

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  1. 16.10Conversion of Vicinal Halohydrinsto Epoxides Dr. Wolf's CHM 201 & 202 16-51

  2. H OH H Br Example H NaOH O H2O H (81%) Dr. Wolf's CHM 201 & 202 16-52

  3. H OH H Br Example H NaOH O H2O H (81%) •• – O via: •• •• H H Br •• •• •• Dr. Wolf's CHM 201 & 202 16-53

  4. Epoxidation via Vicinal Halohydrins Br Br2 H2O OH antiaddition Dr. Wolf's CHM 201 & 202 16-54

  5. Epoxidation via Vicinal Halohydrins corresponds to overall syn addition ofoxygen to the double bond Br Br2 NaOH H2O O OH antiaddition inversion Dr. Wolf's CHM 201 & 202 16-55

  6. Epoxidation via Vicinal Halohydrins corresponds to overall syn addition ofoxygen to the double bond Br H3C Br2 H NaOH H3C H CH3 H H2O H O CH3 OH antiaddition inversion Dr. Wolf's CHM 201 & 202 16-56

  7. Epoxidation via Vicinal Halohydrins corresponds to overall syn addition ofoxygen to the double bond Br H3C Br2 H3C H H NaOH H3C H H CH3 CH3 H H2O H O CH3 OH antiaddition inversion Dr. Wolf's CHM 201 & 202 16-57

  8. 16.11Reactions of Epoxides:A Review and a Preview Dr. Wolf's CHM 201 & 202 16-58

  9. Reactions of Epoxides All reactions involve nucleophilic attack at carbon and lead to opening of the ring. An example is the reaction of ethylene oxide with a Grignard reagent (discussed in Section 15.4 as a method for the synthesis of alcohols). Dr. Wolf's CHM 201 & 202 16-59

  10. R MgX CH2 H2C O Reaction of Grignard Reagentswith Epoxides R CH2 CH2 OMgX H3O+ RCH2CH2OH Dr. Wolf's CHM 201 & 202 16-60

  11. CH2MgCl CH2CH2CH2OH Example CH2 H2C + O 1. diethyl ether 2. H3O+ (71%) Dr. Wolf's CHM 201 & 202 16-61

  12. CH2 H2C O In general... Reactions of epoxides involve attack by anucleophile and proceed with ring-opening.For ethylene oxide: + Nu—H Nu—CH2CH2O—H Dr. Wolf's CHM 201 & 202 16-62

  13. R CH2 C H O In general... For epoxides where the two carbons of thering are differently substituted: Nucleophiles attack herewhen the reaction iscatalyzed by acids: Anionic nucleophilesattack here: Dr. Wolf's CHM 201 & 202 16-63

  14. 16.12Nucleophilic Ring-OpeningReactions of Epoxides Dr. Wolf's CHM 201 & 202 16-64

  15. CH2 H2C O CH3CH2O CH2CH2OH Example NaOCH2CH3 CH3CH2OH (50%) Dr. Wolf's CHM 201 & 202 16-65

  16. – •• CH3CH2 O •• •• CH2 H2C O Mechanism •• •• Dr. Wolf's CHM 201 & 202 16-66

  17. – •• CH3CH2 O •• •• CH2 H2C O •• CH3CH2 O O CH2CH2 •• •• •• Mechanism •• •• – •• Dr. Wolf's CHM 201 & 202 16-67

  18. – •• CH3CH2 O •• •• CH2 H2C O O CH2CH3 •• •• CH3CH2 O O CH2CH2 H •• •• Mechanism •• •• •• – •• •• Dr. Wolf's CHM 201 & 202 16-68

  19. – •• CH3CH2 O •• •• CH2 H2C O O CH2CH3 •• •• CH3CH2 O O CH2CH2 H •• •• •• – O CH2CH3 •• Mechanism •• •• •• – •• •• •• •• CH3CH2 O O CH2CH2 H •• •• •• Dr. Wolf's CHM 201 & 202 16-69

  20. CH2 H2C O CH3CH2CH2CH2S CH2CH2OH Example KSCH2CH2CH2CH3 ethanol-water, 0°C (99%) Dr. Wolf's CHM 201 & 202 16-70

  21. H NaOCH2CH3 H CH3CH2OH O Stereochemistry Inversion of configuration at carbon being attacked by nucleophile Suggests SN2-like transition state OCH2CH3 H H OH (67%) Dr. Wolf's CHM 201 & 202 16-71

  22. Stereochemistry CH3 H3C Inversion of configuration at carbon being attacked by nucleophile Suggests SN2-like transition state R R H NH3 H OH O H2N H R H2O S H H3C CH3 (70%) Dr. Wolf's CHM 201 & 202 16-72

  23. Stereochemistry CH3 H3C R R H NH3 H OH O H2N H R H2O S H H3C CH3 (70%) H3C H d+ d- O H3N H H3C Dr. Wolf's CHM 201 & 202 16-73

  24. CH3O CH3 H3C CH3 CH3CH CCH3 C C OH H CH3 O Anionic nucleophile attacks less-crowded carbon consistent with SN2-like transition state NaOCH3 CH3OH (53%) Dr. Wolf's CHM 201 & 202 16-74

  25. MgBr CHCH3 H2C O CH2CHCH3 OH Anionic nucleophile attacks less-crowded carbon + 1. diethyl ether 2. H3O+ (60%) Dr. Wolf's CHM 201 & 202 16-75

  26. CH(CH2)7CH3 H2C O CH(CH2)7CH3 H3C OH Lithium aluminum hydride reduces epoxides Hydride attacksless-crowdedcarbon 1. LiAlH4, diethyl ether 2. H2O (90%) Dr. Wolf's CHM 201 & 202 16-76

  27. 16.13Acid-Catalyzed Ring-OpeningReactions of Epoxides Dr. Wolf's CHM 201 & 202 16-77

  28. CH2 H2C O Example CH3CH2OCH2CH2OCH2CH3 formed only on heating and/or longer reaction times CH3CH2OH CH3CH2OCH2CH2OH H2SO4, 25°C (87-92%) Dr. Wolf's CHM 201 & 202 16-78

  29. CH2 H2C O Example BrCH2CH2Br formed only on heating and/or longer reaction times HBr BrCH2CH2OH 10°C (87-92%) Dr. Wolf's CHM 201 & 202 16-79

  30. CH2 H2C CH2 H2C + O O •• •• – •• •• Br Br H H •• •• •• •• •• Mechanism •• Dr. Wolf's CHM 201 & 202 16-80

  31. – •• Br •• •• •• CH2 H2C CH2 H2C + O O •• •• •• Br H H •• •• •• Br •• •• H O CH2CH2 •• Mechanism •• •• Dr. Wolf's CHM 201 & 202 16-81

  32. H O H •• + H Figure 16.6 Acid-Catalyzed Hydrolysis of Ethylene Oxide Step 1 CH2 CH2 H2C H2C + O O •• •• H •• H O •• •• H Dr. Wolf's CHM 201 & 202 16-82

  33. H O H •• •• CH2 H2C + O •• H H + O H •• H O CH2CH2 Figure 16.6 Acid-Catalyzed Hydrolysis of Ethylene Oxide Step 2 •• •• Dr. Wolf's CHM 201 & 202 16-83

  34. H + O H •• H H H O •• •• O H •• •• H H O CH2CH2 + O H •• H O CH2CH2 Figure 16.6 Acid-Catalyzed Hydrolysis of Ethylene Oxide Step 3 •• •• •• •• Dr. Wolf's CHM 201 & 202 16-84

  35. Acid-Catalyzed Ring Opening of Epoxides Characteristics: nucleophile attacks more substituted carbon of protonated epoxide inversion of configuration at site of nucleophilic attack Dr. Wolf's CHM 201 & 202 16-85

  36. H3C CH3 C C H CH3 O Nucleophile attacks more-substituted carbon consistent with carbocation character at transition state OCH3 CH3OH CH3CH CCH3 H2SO4 CH3 OH (76%) Dr. Wolf's CHM 201 & 202 16-86

  37. H3C CH3 C H CH3 OH Nucleophile attacks more-substituted carbon consistent with carbocation character at transition state OCH3 CH3OH d+ d+ CH3CH CCH3 C H2SO4 CH3 OH (76%) d+ Dr. Wolf's CHM 201 & 202 16-86b

  38. H O H Stereochemistry H Inversion of configuration at carbon being attacked by nucleophile OH HBr H Br (73%) Dr. Wolf's CHM 201 & 202 16-87

  39. CH3OH H2SO4 Stereochemistry CH3 H3C Inversion of configuration at carbon being attacked by nucleophile R R H H OH O CH3O H R S H H3C CH3 (57%) Dr. Wolf's CHM 201 & 202 16-88

  40. CH3OH H2SO4 Stereochemistry CH3 H3C R R H H OH O CH3O H R S H H3C CH3 H3C H d+ d+ d+ H O CH3O H H H3C Dr. Wolf's CHM 201 & 202 16-89

  41. H O H CH3COOH O H H anti-Hydroxylation of Alkenes H2O HClO4 H OH H OH (80%) Dr. Wolf's CHM 201 & 202 16-90

  42. 16.14Epoxides in Biological Processes Dr. Wolf's CHM 201 & 202 16-91

  43. Naturally Occurring Epoxides are common are involved in numerous biological processes Dr. Wolf's CHM 201 & 202 16-92

  44. C + O2 + H+ C Biosynthesis of Epoxides + NADH enzyme-catalyzed oxygen transfer from O2 to alkene enzymes are referred to as monooxygenases enzyme + + NAD+ C C H2O O Dr. Wolf's CHM 201 & 202 16-93

  45. O Example: biological epoxidation of squalene this reaction is an important step in the biosynthesisof cholesterol O2, NADHmonoxygenase Dr. Wolf's CHM 201 & 202 16-94

  46. 16.15Preparation of Sulfides Dr. Wolf's CHM 201 & 202 16-95

  47. •• •• R R' X R' S •• •• •• CH2 CH2 CH3CHCH CH3CHCH Cl SCH3 Preparation of RSR' prepared by nucleophilic substitution (SN2) – + R S NaSCH3 methanol Dr. Wolf's CHM 201 & 202 16-96

  48. 16.16Oxidation of Sulfides:Sulfoxides and Sulfones Dr. Wolf's CHM 201 & 202 16-97

  49. – •• •• O O •• •• •• •• •• + R R R' R' S S •• •• O •• •• Oxidation of RSR' – either the sulfoxide or the sulfone can be isolated depending on the oxidizing agent and reactionconditions ++ R R' S – •• sulfide sulfoxide sulfone Dr. Wolf's CHM 201 & 202 16-98

  50. – •• O •• •• NaIO4 + •• SCH3 SCH3 •• •• Example Sodium metaperiodate oxidizes sulfides to sulfoxides and no further. water (91%) Dr. Wolf's CHM 201 & 202 16-99

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