1. Dr. Wolf's CHM 201 & 202 15-1 Chapter 15 Alcohols, Diols, and Thiols

2. Dr. Wolf's CHM 201 & 202 15-2 15.1 Sources of Alcohols

3. Dr. Wolf's CHM 201 & 202 15-3 Methanol is an industrial chemical end uses: solvent, antifreeze, fuel principal use: preparation of formaldehyde MethanolMethanol

4. Dr. Wolf's CHM 201 & 202 15-4 Methanol is an industrial chemical end uses: solvent, antifreeze, fuel principal use: preparation of formaldehyde prepared by hydrogenation of carbon monoxide CO + 2H 2  CH 3 OH MethanolMethanol

5. Dr. Wolf's CHM 201 & 202 15-5 Ethanol is an industrial chemical Most ethanol comes from fermentation Synthetic ethanol is produced by hydration of ethylene Synthetic ethanol is denatured (made unfit for drinking) by adding methanol, benzene, pyridine, castor oil, gasoline, etc. EthanolEthanol

6. Dr. Wolf's CHM 201 & 202 15-6 Isopropyl alcohol is prepared by hydration of propene. All alcohols with four carbons or fewer are readily available. Most alcohols with five or six carbons are readily available. Other alcohols

7. Dr. Wolf's CHM 201 & 202 15-7 Hydration of alkenes Hydroboration-oxidation of alkenes Hydrolysis of alkyl halides Syntheses using Grignard reagents organolithium reagents Sources of alcohols Reactions discussed in earlier chapters (Table 15.1)

8. Dr. Wolf's CHM 201 & 202 15-8 Reduction of aldehydes and ketones Reduction of carboxylic acids Reduction of esters Reaction of Grignard reagents with epoxides Diols by hydroxylation of alkenes Sources of alcohols New methods in Chapter 15

9. Dr. Wolf's CHM 201 & 202 15-9 15.2 Preparation of Alcohols by Reduction of Aldehydes and Ketones

10. Dr. Wolf's CHM 201 & 202 15-10 CRHOH H CRH O Reduction of Aldehydes Gives Primary Alcohols

11. Dr. Wolf's CHM 201 & 202 15-11 Pt, ethanol (92%) Example: Catalytic Hydrogenation CH 3 O CH 2 OH O CH 3 O CH + H2H2H2H2

12. Dr. Wolf's CHM 201 & 202 15-12 CRHOH R' C R R' O Reduction of Ketones Gives Secondary Alcohols

13. Dr. Wolf's CHM 201 & 202 15-13 (93-95%) Example: Catalytic Hydrogenation + H2H2H2H2OPt ethanol HOH

14. Dr. Wolf's CHM 201 & 202 15-14 H:–H:–H:–H:– H:–H:–H:–H:– CRH OHOHOHOH H CRH O CRH OHOHOHOH R' CRR' O Retrosynthetic Analysis

15. Dr. Wolf's CHM 201 & 202 15-15 Sodium borohydride Lithium aluminum hydride Li+ Na+ – B HHHH – Al HHHH Metal Hydride Reducing Agents act as hydride donors

16. Dr. Wolf's CHM 201 & 202 15-16 NaBH 4 (82%) Examples: Sodium Borohydride CH 2 OH O CH O2NO2NO2NO2Nmethanol O2NO2NO2NO2N O HOH(84%) NaBH 4 ethanol Aldehyde Ketone

17. Dr. Wolf's CHM 201 & 202 15-17 Lithium aluminum hydride more reactive than sodium borohydride cannot use water, ethanol, methanol etc. as solvents diethyl ether is most commonly used solvent

18. Dr. Wolf's CHM 201 & 202 15-18 Examples: Lithium Aluminum Hydride (84%) Aldehyde KetoneO CH 3 (CH 2 ) 5 CH CH 3 (CH 2 ) 5 CH 2 OH 1. LiAlH 4 diethyl ether 2. H 2 O O (C 6 H 5 ) 2 CHCCH 3 1. LiAlH 4 diethyl ether 2. H 2 O (86%)OH (C 6 H 5 ) 2 CHCHCH 3

19. Dr. Wolf's CHM 201 & 202 15-19 neither NaBH 4 or LiAlH 4 reduces isolated double bonds HOH O 1. LiAlH 4 diethyl ether 2. H 2 O (90%) SelectivitySelectivity

20. Dr. Wolf's CHM 201 & 202 15-20 15.3 Preparation of Alcohols By Reduction of Carboxylic Acids and Esters

21. Dr. Wolf's CHM 201 & 202 15-21 lithium aluminum hydride is only effective reducing agent Reduction of Carboxylic Acids Gives Primary Alcohols CRHOH H C R HO O

22. Dr. Wolf's CHM 201 & 202 15-22 Example: Reduction of a Carboxylic Acid 1. LiAlH 4 diethyl ether 2. H 2 O COH O CH 2 OH (78%)

23. Dr. Wolf's CHM 201 & 202 15-23 Lithium aluminum hydride preferred for laboratory reductions Sodium borohydride reduction is too slow to be useful Catalytic hydrogenolysis used in industry but conditions difficult or dangerous to duplicate in the laboratory (special catalyst, high temperature, high pressure Reduction of Esters Gives Primary Alcohols

24. Dr. Wolf's CHM 201 & 202 15-24 Example: Reduction of an Ester 1. LiAlH 4 diethyl ether 2. H 2 O (90%)O COCH 2 CH 3 CH 3 CH 2 OH CH 2 OH +

25. Dr. Wolf's CHM 201 & 202 15-25 15.4 Preparation of Alcohols From Epoxides

26. Dr. Wolf's CHM 201 & 202 15-26 Reaction of Grignard Reagents with Epoxides CH 2 OMgX H3O+H3O+H3O+H3O+ H2CH2CH2CH2C O RMgXR RCH 2 CH 2 OH

27. Dr. Wolf's CHM 201 & 202 15-27 CH 3 (CH 2 ) 4 CH 2 MgBr H2CH2CH2CH2C CH 2 O + 1. diethyl ether 2. H 3 O + CH 3 (CH 2 ) 4 CH 2 CH 2 CH 2 OH (71%) ExampleExample

28. Dr. Wolf's CHM 201 & 202 15-28 15.5 Preparation of Diols

29. Dr. Wolf's CHM 201 & 202 15-29 Diols are prepared by... reactions used to prepare alcohols hydroxylation of alkenes

30. Dr. Wolf's CHM 201 & 202 15-30 OO HCCH 2 CHCH 2 CH CH 3 H 2 (100 atm) Ni, 125°C HOCH 2 CH 2 CHCH 2 CH 2 OH CH 3 3-Methyl-1,5-pentanediol (81-83%) Example: reduction of a dialdehyde

31. Dr. Wolf's CHM 201 & 202 15-31 vicinal diols have hydroxyl groups on adjacent carbons ethylene glycol (HOCH 2 CH 2 OH) is most familiar example Hydroxylation of Alkenes Gives Vicinal Diols

32. Dr. Wolf's CHM 201 & 202 15-32 syn addition of —OH groups to each carbon of double bond Osmium Tetraoxide is Key Reagent C C HOHOHOHO OHOHOHOH C C O O Os OO C C

33. Dr. Wolf's CHM 201 & 202 15-33 (CH 3 ) 3 COOH OsO 4 (cat) tert-Butyl alcohol HO – ExampleExample (73%) CH 2 CH 3 (CH 2 ) 7 CH CH 3 (CH 2 ) 7 CHCH 2 OH OH

34. Dr. Wolf's CHM 201 & 202 15-34 (CH 3 ) 3 COOH OsO 4 (cat) tert-Butyl alcohol HO – ExampleExample (62%)HH HH OH HO

35. Dr. Wolf's CHM 201 & 202 15-35 15.6 Reactions of Alcohols: A Review and a Preview

36. Dr. Wolf's CHM 201 & 202 15-36 Table 15.2 Review of Reactions of Alcohols reaction with hydrogen halides reaction with thionyl chloride reaction with phosphorous tribromide acid-catalyzed dehydration conversion to p-toluenesulfonate esters

37. Dr. Wolf's CHM 201 & 202 15-37 New Reactions of Alcohols in This Chapter conversion to ethers esterification esters of inorganic acids oxidation cleavage of vicinal diols

38. Dr. Wolf's CHM 201 & 202 15-38 15.7 Conversion of Alcohols to Ethers

39. Dr. Wolf's CHM 201 & 202 15-39 RCH 2 O H CH 2 R OH H+H+H+H+ RCH 2 O CH 2 R HOH+ Conversion of Alcohols to Ethers acid-catalyzed referred to as a "condensation" equilibrium; most favorable for primary alcohols

40. Dr. Wolf's CHM 201 & 202 15-40 ExampleExample 2CH 3 CH 2 CH 2 CH 2 OH H 2 SO 4, 130°C CH 3 CH 2 CH 2 CH 2 OCH 2 CH 2 CH 2 CH 3 (60%)

41. Dr. Wolf's CHM 201 & 202 15-41 Mechanism of Formation of Diethyl Ether Mechanism of Formation of Diethyl Ether Step 1: CH 3 CH 2 O H H OSO 2 OH CH 3 CH 2 O H OSO 2 OH H + – +

42. Dr. Wolf's CHM 201 & 202 15-42 Mechanism of Formation of Diethyl Ether Mechanism of Formation of Diethyl Ether Step 2: CH 3 CH 2 HH+ O CH 3 CH 2 O H + + CH 3 CH 2 CH 3 CH 2 O H HHO

43. Dr. Wolf's CHM 201 & 202 15-43 Mechanism of Formation of Diethyl Ether Mechanism of Formation of Diethyl Ether Step 3: + + CH 3 CH 2 CH 3 CH 2 O H OSO 2 OH – H OSO 2 OH CH 3 CH 2 CH 3 CH 2 O

44. Dr. Wolf's CHM 201 & 202 15-44 reaction normally works well only for 5- and 6-membered rings Intramolecular Analog HOCH 2 CH 2 CH 2 CH 2 CH 2 OH H 2 SO 4 130° O (76%)

45. Dr. Wolf's CHM 201 & 202 15-45 Intramolecular Analog HOCH 2 CH 2 CH 2 CH 2 CH 2 OH H 2 SO 4 130° O (76%) via: O H + O H H