1. Created by Professor William Tam & Dr. Phillis Chang Ch. 11 - 1 Chapter 11 Alcohols & Ethers

2. Ch. 11 - 2 1.Structure & Nomenclature  Alcohols have a hydroxyl (–OH) group bonded to a saturated carbon atom (sp 3 hybridized) 1o1o 2o2o 3o3o Ethanol2-Propanol (isopropyl alcohol) 2-Methyl- 2-propanol (tert-butyl alcohol)

3. Ch. 11 - 3

4. Ch. 11 - 4  Phenols ●Compounds that have a hydroxyl group attached directly to a benzene ring

5. Ch. 11 - 5  Ethers ●The oxygen atom of an ether is bonded to two carbon atoms

6. Ch. 11 - 6 1A.Nomenclature of Alcohols  Rules of naming alcohols ●Identify the longest carbon chain that includes the carbon to which the –OH group is attached ●Use the lowest number for the carbon to which the –OH group is attached ●Alcohol as parent (suffix)  ending with “ol”

7. Ch. 11 - 7  Examples

8. Ch. 11 - 8  Example 3-Propyl-2-heptanol

9. Ch. 11 - 9 1B.Nomenclature of Ethers  Rules of naming ethers ●Similar to those with alkyl halides  CH 3 O–Methoxy  CH 3 CH 2 O–Ethoxy  Example

10. Ch. 11 - 10  Cyclic ethers

11. Ch. 11 - 11 2.Physical Properties of Alcohols and Ethers

12. Ch. 11 - 12  Water solubility of ethers and alcohols ●Both ethers and alcohols are able to form hydrogen bonds with water ●Ethers have solubilities in water that are similar to those of alcohols of the same molecular weight and that are very different from those of hydrocarbons ●The solubility of alcohols in water gradually decreases as the hydrocarbon portion of the molecule lengthens; long- chain alcohols are more “alkane-like” and are, therefore, less like water

13. Ch. 11 - 13  Physical Properties of Ethers NameFormulamp ( o C) bp ( o C) (1 atm)

14. Ch. 11 - 14  Physical Properties of Alcohols NameFormulamp ( o C) bp ( o C) (1 atm) * * Water solubility (g/100 mL H 2 O)

15. Ch. 11 - 15 4. Synthesis of Alcohols from Alkenes  Acid-catalyzed Hydration of Alkenes

16. Ch. 11 - 16  Hydroboration–Oxidation

17. Ch. 11 - 17 H +, H 2 O or 1. Hg(OAc) 2, H 2 O, THF 2. NaBH 4, NaOH 1. BH 3 THF 2. H 2 O 2, NaOH Markovnikov regioselectivity Anti-Markovnikov regioselectivity

18. Ch. 11 - 18 5.Reactions of Alcohols  The reactions of alcohols have mainly to do with the following ●The oxygen atom of the –OH group is nucleophilic and weakly basic ●The hydrogen atom of the –OH group is weakly acidic ●The –OH group can be converted to a leaving group so as to allow substitution or elimination reactions

19. Ch. 11 - 19 C–O & O–H bonds of an alcohol are polarized  Protonation of the alcohol converts a poor leaving group (OH ⊖ ) into a good one (H 2 O)

20. Ch. 11 - 20  Once the alcohol is protonated substitution reactions become possible The protonated –OH group is a good leaving group (H 2 O)

21. Ch. 11 - 21 6.Alcohols as Acids  Alcohols have acidities similar to that of water pK a Values for Some Weak Acids AcidpKapKa CH 3 OH15.5 H2OH2O15.74 CH 3 CH 2 OH15.9 (CH 3 ) 3 COH18.0

22. Ch. 11 - 22  Relative Acidity H 2 O & alcohols are the strongest acids in this series Increasing acidity  Relative Basicity OH ⊖ is the weakest acid in this series Increasing basicity

23. Ch. 11 - 23 7.Conversion of Alcohols into Alkyl Halides ●HX (X = Cl, Br, I) ●PBr 3 ●SOCl 2

24. Ch. 11 - 24  Examples

25. Ch. 11 - 25 8.Alkyl Halides from the Reaction of Alcohols with Hydrogen Halides  The order of reactivity of alcohols ●3o●3o  The order of reactivity of the hydrogen halides ●HI > HBr > HCl (HF is generally unreactive) > 2 o > 1 o < methyl

26. Ch. 11 - 26 OH ⊖ is a poor leaving group H 3 O ⊕ is a good leaving group

27. Ch. 11 - 27 9.Alkyl Halides from the Reaction of Alcohols with PBr 3 or SOCl 2  Reaction of alcohols with PBr 3 ●The reaction does not involve the formation of a carbocation and usually occurs without rearrangement of the carbon skeleton (especially if the temperature is kept below 0°C)

28. Ch. 11 - 28  Mechanism

29. Ch. 11 - 29  Reaction of alcohols with SOCl 2 ●SOCl 2 converts 1 o and 2 o alcohols to alkyl chlorides ●As with PBr 3, the reaction does not involve the formation of a carbocation and usually occurs without rearrangement of the carbon skeleton (especially if the temperature is kept below 0°C) ●Pyridine (C 5 H 5 N) is often included to promote the reaction

30. Ch. 11 - 30  Mechanism

31. Ch. 11 - 31  Mechanism Cl ⊖

32. Ch. 11 - 32 10.Tosylates, Mesylates, & Triflates: Leaving Group Derivatives of Alcohols

33. Ch. 11 - 33  Direct displacement of the –OH group with a nucleophile via an S N 2 reaction is not possible since OH ⊖ is a very poor leaving group  Thus we need to convert the OH ⊖ to a better leaving group first

34. Ch. 11 - 34  Mesylates (OMs) and Tosylates (OTs) are good leaving groups and they can be prepared easily from an alcohol (methane sulfonyl chloride)

35. Ch. 11 - 35  Preparation of Tosylates (OTs) from an alcohol (p-toluene sulfonyl chloride)

36. Ch. 11 - 36  S N 2 displacement of the mesylate or tosylate with a nucleophile is possible

37. Ch. 11 - 37  Example Retention of configuration Inversion of configuration

38. Ch. 11 - 38  Example Retention of configuration Inversion of configuration

39. Ch. 11 - 39 11.Synthesis of Ethers 11A. Ethers by Intermolecular Dehydration of Alcohols

40. Ch. 11 - 40  Mechanism ●This method is only good for synthesis of symmetrical ethers

41. Ch. 11 - 41  For unsymmetrical ethers Mixture of ethers 1 o alcohols

42. Ch. 11 - 42  Exception

43. Ch. 11 - 43 11B. The Williamson Synthesis of Ethers  Via S N 2 reaction, thus R is limited to 1 o (but R ' can be 1 o, 2 o or 3 o )

44. Ch. 11 - 44  Example 1

45. Ch. 11 - 45  Example 2

46. Ch. 11 - 46  Example 3  However

47. Ch. 11 - 47 11C. Synthesis of Ethers by Alkoxy- mercuration – Demercuration Markovnikov regioselectivity

48. Ch. 11 - 48  Example

49. Ch. 11 - 49 11D. tert-Butyl Ethers by Alkylation of Alcohols: Protecting Groups  A tert-butyl ether can be used to “protect” the hydroxyl group of a 1 o alcohol while another reaction is carried out on some other part of the molecule  A tert-butyl protecting group can be removed easily by treating the ether with dilute aqueous acid

50. Ch. 11 - 50  Example

51. Ch. 11 - 51 ●Direct reaction will not work ☓ (Not Formed) ●Since Grignard reagents are basic and alcohols contain acidic proton

52. Ch. 11 - 52 ●Need to “protect” the –OH group first tert-butyl protected alcohol deprotonation

53. Ch. 11 - 53 12.Reactions of Ethers  Dialkyl ethers react with very few reagents other than acids

54. Ch. 11 - 54 12A. Cleavage of Ethers  Heating dialkyl ethers with very strong acids (HI, HBr, and H 2 SO 4 ) causes them to undergo reactions in which the carbon–oxygen bond breaks Cleavage of an ether

55. Ch. 11 - 55  Mechanism

56. Ch. 11 - 56 13.Epoxides  Epoxide (oxirane) ●A 3-membered ring containing an oxygen

57. Ch. 11 - 57 13A. Synthesis of Epoxides: Epoxidation  Electrophilic epoxidation

58. Ch. 11 - 58  Peroxy acids (peracids) ●Common peracids

59. Ch. 11 - 59 13B. Stereochemistry of Epoxidation  Addition of peroxy acid across a C=C bond  A stereospecific syn (cis) addition

60. Ch. 11 - 60 14.Reactions of Epoxides  The highly strained three-membered ring of epoxides makes them much more reactive toward nucleophilic substitution than other ethers

61. Ch. 11 - 61  Acid-catalyzed ring opening of epoxide

62. Ch. 11 - 62  Base-catalyzed ring opening of epoxide

63. Ch. 11 - 63  If the epoxide is unsymmetrical, in the base-catalyzed ring opening, attack by the alkoxide ion occurs primarily at the less substituted carbon atom 1 o carbon atom is less hindered

64. Ch. 11 - 64  In the acid-catalyzed ring opening of an unsymmetrical epoxide the nucleophile attacks primarily at the more substituted carbon atom This carbon resembles a 3 o carbocation

65. Ch. 11 - 65 15.Anti 1,2-Dihydroxylation of Alkenes via Epoxides  Synthesis of 1,2-diols

66. Ch. 11 - 66  Anti-Dihydroxylation ●A 2-step procedure via ring-opening of epoxides

67. Ch. 11 - 67 16.Crown Ethers  Crown ethers are heterocycles containing many oxygens  They are able to transport ionic compounds in organic solvents – phase transfer agent

68. Ch. 11 - 68  Crown ether names: x-crown-y ●x = ring size ●y = number of oxygen

69. Ch. 11 - 69  Different crown ethers accommodate different guests in this guest-host relationship ●18-crown-6 for K + ●15-crown-5 for Na + ●12-crown-4 for Li +  1987 Nobel Prize to Charles Pedersen (Dupont), D.J. Cram (UCLA) and J.M. Lehn (Strasbourg) for their research on ion transport, crown ethers

70. Ch. 11 - 70  Many important implications to biochemistry and ion transport

71. Ch. 11 - 71 17.Summary of Reactions of Alkenes, Alcohols, and Ethers  Synthesis of alcohols

72. Ch. 11 - 72  Synthesis of alcohols

73. Ch. 11 - 73  Synthesis of alcohols

74. Ch. 11 - 74  Reaction of alcohols

75. Ch. 11 - 75  Synthesis of ethers  Cleavage reaction of ethers