1. 15.6 Reactions of Alcohols: A Review and a Preview

2. 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

3. New Reactions of Alcohols in This Chapter conversion to ethers esterification esters of inorganic acids oxidation cleavage of vicinal diols

4. 15.7 Conversion of Alcohols to Ethers

5. 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

6. Example 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%)

7. Figure 15.2 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 + – +

8. Figure 15.2 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

9. Figure 15.2 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

10. 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%)

11. 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

12. 15.8 Esterification

13. condensation Fischer esterification acid catalyzed reversible Esterification ROH H2OH2OH2OH2O + H+H+H+H+ + R'COHO R'COR O

14. Example of Fischer Esterification H2OH2OH2OH2O + CH 3 OH + COHO COCH 3 O H 2 SO 4 0.1 mol 0.6 mol 70% yield based on benzoic acid

15. high yields not reversible when carried out in presence of pyridine Reaction of Alcohols with Acyl Chlorides ROH HCl ++ R'CClO R'COR O

16. pyridine + CCl O2NO2NO2NO2NO CH 3 CH 2 CH 3 OHOHOHOH (63%) NO 2 CH 3 CH 2 CH 3 OCOCOCOC O Example

17. analogous to reaction with acyl chlorides Reaction of Alcohols with Acid Anhydrides ROH ++ R'COR O O R'COCR'O R'COHO

18. pyridine (83%) + C 6 H 5 CH 2 CH 2 OH O F 3 CCOCCF 3 O C 6 H 5 CH 2 CH 2 OCCF 3 OExample

19. 15.9 Esters of Inorganic Acids

20. Esters of Inorganic Acids ROH + HOEWG ROEWG + H 2 O EWG is an electron-withdrawing group HONO 2 (HO) 2 SO 2 (HO) 3 P O+–

21. Esters of Inorganic Acids ROH + HOEWG ROEWG + H 2 O EWG is an electron-withdrawing group HONO 2 (HO) 2 SO 2 (HO) 3 P O+– CH 3 OH + HONO 2 CH 3 ONO 2 + H 2 O (66-80%)

22. 15.10 Oxidation of Alcohols

23. Primary alcohols Secondary alcohols from H 2 O Oxidation of Alcohols RCH 2 OH ORCHORCOHORCR' RCHR'OH

24. Aqueous solution Mn(VII) Cr(VI) KMnO 4 H 2 CrO 4 KMnO 4 H 2 CrO 4 H 2 Cr 2 O 7 Typical Oxidizing Agents

25. Aqueous Cr(VI) FCH 2 CH 2 CH 2 CH 2 OH K 2 Cr 2 O 7 H 2 SO 4 H2OH2OH2OH2O FCH 2 CH 2 CH 2 COH (74%)O

26. Aqueous Cr(VI) FCH 2 CH 2 CH 2 CH 2 OH K 2 Cr 2 O 7 H 2 SO 4 H2OH2OH2OH2O FCH 2 CH 2 CH 2 COH (74%)O Na 2 Cr 2 O 7 H 2 SO 4 H2OH2OH2OH2O (85%)HOH O

27. All are used in CH 2 Cl 2 Pyridinium dichromate (PDC) (C 5 H 5 NH + ) 2 Cr 2 O 7 2– Pyridinium chlorochromate (PCC) C 5 H 5 NH + ClCrO 3 – Nonaqueous Sources of Cr(VI)

28. Example: Oxidation of a primary alcohol with PCC CH 3 (CH 2 ) 5 CH 2 OH PCC CH 2 Cl 2 O CH 3 (CH 2 ) 5 CH (78%) ClCrO 3 – N H +

29. PDC CH 2 Cl 2 O(94%) CH 2 OH (CH 3 ) 3 C CH Example: Oxidation of a primary alcohol with PDC

30. Mechanism involves formation and elimination of a chromate ester C OHOHOHOH HOCrOH OO C O H HOO CrOH

31. Mechanism involves formation and elimination of a chromate ester C OHOHOHOH HOCrOH OO C O H HOO CrOH O CO

32. 15.11 Biological Oxidation of Alcohols

33. alcoholdehydrogenase Enzyme-catalyzed CH 3 CH 2 OH + NAD++ ++H NADH CH 3 CH O

34. nicotinamide adenine dinucleotide (oxidized form) HO HO O O N N NH 2 P O P O O HO OH H C O N O O OO + __ Figure 15.3 Structure of NAD +

35. Enzyme-catalyzed CH 3 CH 2 OH + N H CNH 2 O+ R +H +

36. Enzyme-catalyzed N H OR CH 3 CH OH

37. 15.12 Oxidative Cleavage of Vicinal Diols

38. Cleavage of Vicinal Diols by Periodic Acid CC HO OH HIO 4 C O O C +

39. Cleavage of Vicinal Diols by Periodic Acid HIO 4 CH CCH 3 CH 3 OHHO CH 3 CCH 3 OCHO+ (83%)

40. Cyclic Diols are Cleaved HIO 4 OHOH O HCCH 2 CH 2 CH 2 CH O