15.6 Reactions of Alcohols: A Review and a Preview Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Table 15.2 Review of Reactions of Alcohols Reaction with hydrogen halides Reaction with thionyl chloride Reaction with phosphorous trihalides Acid-catalyzed dehydration Conversion to p-toluenesulfonate esters

New Reactions of Alcohols in This Chapter Conversion to ethers Esterification Oxidation Cleavage of vicinal diols

15.7 Conversion of Alcohols to Ethers

RCH 2 O H CH 2 R OH H+H+ RCH 2 OCH 2 RHOH+ Conversion of Alcohols to Ethers Acid-catalyzed Referred to as a "condensation" Equilibrium; most favorable for primary alcohols

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%)

Mechanism of Formation of Diethyl Ether Step 1: H H OSO 2 OH H H CH 3 CH 2 O OSO 2 OH + – + CH 3 CH 2 O

Mechanism of Formation of Diethyl Ether Step 2: H CH 3 CH 2 H + O CH 3 CH 2 O H + + CH 3 CH 2 CH 3 CH 2 O H H H O

Step 3: + CH 3 CH 2 CH 3 CH 2 O H OCH 2 CH 3 H + CH 3 CH 2 CH 3 CH 2 O OCH 2 CH 3 H H + Mechanism of Formation of Diethyl Ether

Intramolecular Analogue HOCH 2 CH 2 CH 2 CH 2 CH 2 OH H 2 SO 4 130° O (76%) via: O H + O H H Reaction normally works well only for 5- and 6-membered rings.

15.8 Esterification

condensation Fischer esterification acid catalyzed reversible Esterification ROHH2OH2O + H+H+ + R'COH O R'COR O

Example of Fischer Esterification H2OH2O + CH 3 OH + COH O COCH 3 O H 2 SO mol0.6 mol 70% yield based on benzoic acid

High yields Not reversible when carried out in presence of pyridine. Reaction of Alcohols with Acyl Chlorides ROHHCl ++ R'CCl O R'COR O

pyridine + CCl O2NO2N O CH 3 CH 2 CH 3 OHOH (63%) NO 2 CH 3 CH 2 CH 3 OCOC O Example

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

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 O Example

15.9 Oxidation of Alcohols

Primary alcohols from H 2 O Oxidation of Alcohols RCH 2 OH O RCH O RCOH Secondary alcohols O RCR'RCHR' OH

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

Aqueous Cr(VI) FCH 2 CH 2 CH 2 CH 2 OH K 2 Cr 2 O 7 H 2 SO 4 H2OH2O FCH 2 CH 2 CH 2 COH (74%) O Na 2 Cr 2 O 7 H 2 SO 4 H2OH2O (85%) H OH O

Mechanism Involves formation and elimination of a chromate ester. C OHOH HOCrOH O O H C O H O O CrOH C O O HH

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)

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 +

PDCCH 2 Cl 2 O (94%) CH 2 OH (CH 3 ) 3 C CH (CH 3 ) 3 C Example: Oxidation of a Primary Alcohol with PDC

15.10 Biological Oxidation of Alcohols

alcohol dehydrogenase Enzyme-catalyzed CH 3 CH 2 OH + NAD H H CH 3 CH O

nicotinamide adenine dinucleotide (oxidized form) Figure 15.2 Structure of NAD +

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

Enzyme-catalyzed N H CNH 2 O R CH 3 CH O H

15.11 Oxidative Cleavage of Vicinal Diols

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

Cleavage of Vicinal Diols by Periodic Acid HIO 4 CHCCH 3 CH 3 OHHO CH 3 CCH 3 O CH O + (83%)

Cyclic Diols are Cleaved HIO 4 OH O HCCH 2 CH 2 CH 2 CH O