Chapter 15 Alcohols, Diols, and Thiols

1. Chapter 15Alcohols, Diols, and Thiols

2. 15.1Sources of Alcohols

3. Methanol is an industrial chemical: solvent, antifreeze, fuel. Principal use: preparation of formaldehyde. Prepared by hydrogenation of carbon monoxide. Methanol CO + 2H2 CH3OH

4. Ethanol is an industrial chemical. Most ethanol comes from fermentation. Synthetic ethanol is produced by hydrationof ethylene. Synthetic ethanol is denatured 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. Natural Product Alcohols Natural product - Any organic substance isolated from living organisms or material derived from living organisms.

7. Review - Preparation of Alcohols Hydration of alkenes Hydroboration-oxidation of alkenes Nucleophilic 1,2-addition of organometallic reagents to carbonyl compounds

8. Reduction of aldehydes and ketones. Reduction of carboxylic acids. Reduction of esters. Reaction of Grignard reagents with epoxides. 1,2-Diols by dihydroxylation of alkenes. New Ways to Prepare Alcohols

9. 15.2Preparation of AlcoholsbyReduction of Aldehydes and Ketones

10. R R H OH C O C H H Reduction of Aldehydes Gives Primary Alcohols

11. O + CH3O CH H2 CH3O CH2OH Example: Catalytic Hydrogenation Pt, ethanol (92%)

12. R H OH C R' Reduction of Ketones Gives Secondary Alcohols R C O R'

13. O Example: Catalytic Hydrogenation H OH Pt + H2 ethanol (93-95%)

14. R R C O H OH C H H R R H:– H OH C O C R' R' Retrosynthetic Analysis H:–

15. Both act as hydride (H:–) donors. H H – + – + H H Li Na H H Al B H H Lithiumaluminum hydride Metal Hydride Reducing Agents Sodiumborohydride

16. O2N O2N O CH2OH CH (82%) H OH O (84%) Sodium Borohydride Aldehyde NaBH4 methanol Ketone NaBH4 ethanol

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

18. O CH3(CH2)5CH2OH CH3(CH2)5CH (86%) OH O (C6H5)2CHCHCH3 (84%) Lithium Aluminum Hydride Aldehyde LiAlH4, diethyl ether 2. H2O Ketone LiAlH4, diethyl ether (C6H5)2CHCCH3 2. H2O

19. Neither NaBH4 or LiAlH4reduces carbon-carbondouble bonds. O LiAlH4, diethyl ether 2. H2O (90%) H OH Selectivity

20. 15.3Preparation of Alcohols By Reductionof Carboxylic Acids and Esters

21. Lithium aluminum hydride is only effective reducing agent. R H OH C H Reduction of Carboxylic AcidsGives Primary Alcohols R C O HO

22. O COH CH2OH Reduction of a Carboxylic Acid LiAlH4, diethyl ether 2. H2O (78%)

23. Lithium aluminum hydride preferred forlaboratory reductions. Catalytic hydrogenation used in industrybut conditions difficult or dangerous to duplicate in the laboratory (special catalyst, hightemperature, high pressure). Reduction of EstersGives Primary Alcohols

24. O COCH2CH3 LiAlH4, diethyl ether 2. H2O + CH3CH2OH CH2OH (90%) Reduction of an Ester

25. 15.4Preparation of Alcohols From Epoxides

26. CH3(CH2)4CH2CH2CH2OH (71%) Reaction of Grignard Reagentswith Epoxides CH2 H2C CH3(CH2)4CH2MgBr + O 1. diethyl ether 2. H3O+

27. Reaction of Grignard Reagentswith Epoxides Epoxide rings are strained (~29 kcal mol-1) and prone to nucleophilic attack at the carbon centers.

28. 15.5Preparation of Diols

29. O O HCCH2CHCH2CH CH3 HOCH2CH2CHCH2CH2OH CH3 3-Methyl-1,5-pentanediol (81-83%) Example: Reduction of a Dialdehyde H2 (100 atm) Ni, 125°C

30. Vicinal diols have hydroxyl groups on adjacent carbons. Ethylene glycol (HOCH2CH2OH), an antifreeze, is a familiar example. Hydroxylation of AlkenesGives Vicinal Diols

31. C C C C HO OH C C O O Os Cyclic osmate ester O O Osmium Tetraoxide is Key Reagent OsO4

32. CH3(CH2)7CH CH2 (CH3)3COOH,OsO4 (cat), tert-Butyl alcohol,HO– CH3(CH2)7CHCH2OH OH (73%) Example

33. Dihydroxylation with OsO4 Is a Sterespecific Reaction Only the cis-1,2-diol obtained because of the mechanism of initial cycloaddition step: both oxygen atoms on OsO4 attack same face of the alkene.

34. 15.6Reactions of Alcohols:A Review and a Preview

35. Reaction with hydrogen halides (alkyl halides). Reaction with thionyl chloride (alkyl chlorides). Reaction with phosphorous tribromide (alkyl bromides). Acid-catalyzed dehydration (alkenes). Conversion to p-toluenesulfonate esters (tosylates). Review of Reactions of Alcohols

36. Conversion to ethers Esterification Esters of inorganic acids Oxidation Cleavage of vicinal diols New Reactions of Alcohols

37. 15.7Conversion of Alcohols to Ethers

38. Conversion of Alcohols to Ethers Acid-catalyzed condensation of alcohols is an equilibrium reaction; most favorable for primary alcohols and works best if water is removed.

39. Example

40. •• OSO2OH H CH3CH2O •• H + – + OSO2OH CH3CH2O •• H Mechanism of Formation of Diethyl Ether Step 1: H

41. H H CH3CH2 CH3CH2 O + O •• + •• •• + CH3CH2O H •• H •• H CH3CH2O •• H Mechanism of Formation of Diethyl Ether Unlike hydroxide (HO-), H2O is an excellent leaving group, so acid catalysis is the key. Step 2:

42. CH3CH2 CH3CH2 + + CH3CH2O CH3CH2O •• •• •• H •• OCH2CH3 H •• H OCH2CH3 •• + H Mechanism of Formation of Diethyl Ether Step 3:

43. Intramolecular Etherification

44. 15.8Esterification

45. Esterification: A Reversible Process 1) Fischer esterification (a classical transformation). 2) Condensation process (H2O produced). 3) Acid-catalyzed (H2SO4 is source of H+ and dehydrating agent). 4) Reversible - aqueous acid hydrolyzesesters to carboxylic acids. Acidic Dehydration Acid + Alcohol Ester + Water Acidic Hydrolysis

46. Example of Fischer Esterification

47. Reaction of Alcohols with Acyl Chlorides Advantages over Fischer Esterification? Fast, high yields, mild conditions and not reversible.

48. Example

49. Reaction of Alcohols with Acid Anhydrides Note similar behavior of acid anhydrides to acyl chlorides.

50. Example