15.6 Reactions of Alcohols: A Review and a Preview

1. 15.6Reactions 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. 15.7Conversion of Alcohols to Ethers

5. RCH2O CH2R H OH RCH2O CH2R H OH Conversion of Alcohols to Ethers acid-catalyzed referred to as a "condensation" equilibrium; most favorable for primary alcohols H+ +

6. H2SO4, 130°C Example 2CH3CH2CH2CH2OH CH3CH2CH2CH2OCH2CH2CH2CH3 (60%)

7. •• OSO2OH H CH3CH2O •• Figure 15.2 Mechanism of Formation of Diethyl Ether Step 1: H H + – + OSO2OH CH3CH2O •• H

8. H H CH3CH2 CH3CH2 O O •• + •• •• + CH3CH2O H •• H •• H CH3CH2O •• H Figure 15.2 Mechanism of Formation of Diethyl Ether Step 2: +

9. CH3CH2 CH3CH2 + CH3CH2O CH3CH2O •• •• •• H •• •• OSO2OH OSO2OH H •• •• •• – Figure 15.2 Mechanism of Formation of Diethyl Ether Step 3: +

10. O Intramolecular Analog HOCH2CH2CH2CH2CH2OH reaction normally works wellonly for 5- and 6-memberedrings 130° H2SO4 (76%)

11. H •• + O •• O •• H O H Intramolecular Analog HOCH2CH2CH2CH2CH2OH via: 130° H2SO4 (76%)

12. 15.8Esterification

13. O O R'COH R'COR Esterification condensation Fischer esterification acid catalyzed reversible H+ + + ROH H2O

14. O + COH CH3OH H2SO4 O COCH3 Example of Fischer Esterification 70% yield based on benzoic acid 0.1 mol 0.6 mol + H2O

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

16. CH3CH2 O O2N OH CCl CH3 CH3CH2 O NO2 OC CH3 Example + pyridine (63%)

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

18. O O + C6H5CH2CH2OH F3CCOCCF3 O C6H5CH2CH2OCCF3 Example pyridine (83%)

19. 15.9Esters of Inorganic Acids

20. + (HO)3P O Esters of Inorganic Acids ROH + HOEWG ROEWG + H2O EWG is an electron-withdrawing group – HONO2 (HO)2SO2

21. + (HO)3P O Esters of Inorganic Acids ROH + HOEWG ROEWG + H2O EWG is an electron-withdrawing group – HONO2 (HO)2SO2 CH3OH + HONO2 CH3ONO2 + H2O (66-80%)

22. 15.10Oxidation of Alcohols

23. O O O OH RCHR' Oxidation of Alcohols Primary alcohols RCH2OH RCH RCOH Secondary alcohols from H2O RCR'

24. Typical Oxidizing Agents Aqueous solution Mn(VII) Cr(VI) KMnO4 H2CrO4 H2Cr2O7

25. O Aqueous Cr(VI) FCH2CH2CH2CH2OH H2SO4 K2Cr2O7 H2O FCH2CH2CH2COH (74%)

26. H OH O O Aqueous Cr(VI) FCH2CH2CH2CH2OH H2SO4 K2Cr2O7 H2SO4 H2O Na2Cr2O7 H2O FCH2CH2CH2COH (74%) (85%)

27. Nonaqueous Sources of Cr(VI) All are used in CH2Cl2 Pyridinium dichromate (PDC) (C5H5NH+)2 Cr2O72– Pyridinium chlorochromate (PCC) C5H5NH+ ClCrO3–

28. N + H O CH3(CH2)5CH Example: Oxidation of a primary alcohol with PCC ClCrO3– PCC CH3(CH2)5CH2OH CH2Cl2 (78%)

29. (CH3)3C CH2OH O (CH3)3C CH Example: Oxidation of a primary alcohol with PDC PDC CH2Cl2 (94%)

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

31. •• O •• O O O O C O Mechanism H H involves formation and elimination of a chromate ester C C HOCrOH CrOH OH O

32. 15.11Biological Oxidation of Alcohols

33. + NAD + H O NAD CH3CH H Enzyme-catalyzed + CH3CH2OH alcohol dehydrogenase + +

34. _ _ O O O O H P P O O O O O NH2 HO N + C OH N HO HO N O NH2 Figure 15.3 Structure of NAD+ nicotinamide adenine dinucleotide (oxidized form)

35. O H CNH2 + H + N R Enzyme-catalyzed + CH3CH2OH +

36. O O CNH2 CH3CH Enzyme-catalyzed H H •• N R

37. 15.12Oxidative Cleavage of Vicinal Diols

38. HIO4 C C C O O HO OH Cleavage of Vicinal Diols by Periodic Acid + C

39. CH3 CH CCH3 HO OH O O CH CH3CCH3 Cleavage of Vicinal Diols by Periodic Acid HIO4 + (83%)

40. OH O O HCCH2CH2CH2CH OH Cyclic Diols are Cleaved HIO4