1. Chapter 15 Alcohols, Diols, and Thiols Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

2. 15.1 Sources of Alcohols

3. 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 Methanol

4. 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. Ethanol

5. 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

6. 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)

7. Reduction of aldehydes and ketones Reduction of carboxylic acids Reaction of Grignard reagents with epoxides Diols by hydroxylation of alkenes Sources of Alcohols New methods in Chapter 15

8. 15.2 Preparation of Alcohols by Reduction of Aldehydes and Ketones

9. C R HOHOH H C R H O Reduction of Aldehydes Gives Primary Alcohols

10. Pt, ethanol (92%) Example: Catalytic Hydrogenation CH 3 OCH 2 OH O CH 3 OCH + H2H2

11. C R HOHOH R' C R O Reduction of Ketones Gives Secondary Alcohols

12. (93-95%) Example: Catalytic Hydrogenation + H2H2 O Pt ethanol HOH

13. H:–H:– C R HOHOH H C R H O H:–H:– C R HOHOH R' C R O Retrosynthetic Analysis

14. Sodium borohydride Na + – B H H HH Lithium aluminum hydride Li + – Al H H HH Metal Hydride Reducing Agents act as hydride donors

15. Examples: Sodium Borohydride O CH O2NO2N O NaBH 4 methanol (82%) CH 2 OH O2NO2N HOH (84%) NaBH 4 ethanol Aldehyde Ketone

16. Lithium Aluminum Hydride More reactive than sodium borohydride. Cannot use water, ethanol, methanol etc. as solvents. Diethyl ether is most commonly used solvent.

17. Examples: Lithium Aluminum Hydride Aldehyde Ketone O CH 3 (CH 2 ) 5 CH 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 (84%) CH 3 (CH 2 ) 5 CH 2 OH (86%) OH (C 6 H 5 ) 2 CHCHCH 3

18. Neither NaBH 4 or LiAlH 4 reduces carbon-carbon double bonds. O HOH 1. LiAlH 4 diethyl ether 2. H 2 O (90%) Selectivity

19. 15.3 Preparation of Alcohols By Reduction of Carboxylic Acids

20. lithium aluminum hydride is only effective reducing agent Reduction of Carboxylic Acids Gives Primary Alcohols C R HOHOH H C R HO O

21. Example: Reduction of a Carboxylic Acid 1. LiAlH 4 diethyl ether 2. H 2 O COH O CH 2 OH (78%)

22. 15.4 Preparation of Alcohols From Epoxides

23. Reaction of Grignard Reagents with Epoxides H2CH2C CH 2 O RMgX CH 2 OMgX R H3O+H3O+ RCH 2 CH 2 OH

24. CH 3 (CH 2 ) 4 CH 2 MgBr H2CH2C CH 2 O + 1. diethyl ether 2. H 3 O + CH 3 (CH 2 ) 4 CH 2 CH 2 CH 2 OH (71%) Example

25. 15.5 Preparation of Diols

26. Diols are Prepared by... Reactions used to prepare alcohols Hydroxylation of alkenes

27. O O 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

28. 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

29. Osmium Tetraoxide is Key Reagent C C HOHO OHOH C C OsO 4 O O Os OO C C Cyclic osmate ester

30. (CH 3 ) 3 COOH OsO 4 (cat) tert-Butyl alcohol HO – Example (73%) CH 2 CH 3 (CH 2 ) 7 CH CH 3 (CH 2 ) 7 CHCH 2 OH OHOH

31. Example H H (CH 3 ) 3 COOH OsO 4 (cat) tert-Butyl alcohol HO – (62%) H H OHOH HOHO Stereospecific syn addition of —OH groups to each carbon of double bond