15.6 Reactions of Alcohols: A Review and a Preview

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

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

15.7 Conversion of Alcohols to Ethers

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

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%)

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 + – +

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

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

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%)

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

15.8 Esterification

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

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

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

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

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

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

15.9 Esters of Inorganic Acids

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+–

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%)

15.10 Oxidation of Alcohols

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

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

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

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

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 +

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

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

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

15.11 Biological Oxidation of Alcohols

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

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 +

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

Enzyme-catalyzed N H OR CH 3 CH OH

15.12 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 CH CCH 3 CH 3 OHHO CH 3 CCH 3 OCHO+ (83%)

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