Chapter 15 Alcohols, Diols, and Thiols Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Sources of Alcohols

Hydration of alkenes Hydroboration-oxidation of alkenes Hydrolysis of alkyl halides Syntheses using Grignard reagents Organolithium reagents Sources of Alcohols Reactions discussed in earlier chapters (Table 15.1)

Reduction of aldehydes and ketones Reduction of carboxylic acids Reaction of Grignard reagents with epoxides Diols by hydroxylation of alkenes Sources of Alcohols New methods in Chapter 15

Preparation of Alcohols by Reduction of Aldehydes and Ketones

C R HOHOH H C R H O Reduction of Aldehydes Gives Primary Alcohols

Pt, ethanol (92%) Example: Catalytic Hydrogenation CH 3 OCH 2 OH O CH 3 OCH + H2H2

C R HOHOH R' C R O Reduction of Ketones Gives Secondary Alcohols

(93-95%) Example: Catalytic Hydrogenation + H2H2 O Pt ethanol HOH

H:–H:– C R HOHOH H C R H O H:–H:– C R HOHOH R' C R O Retrosynthetic Analysis

Sodium borohydride Na + – B H H HH Lithium aluminum hydride Li + – Al H H HH Metal Hydride Reducing Agents act as hydride donors

Examples: Sodium Borohydride O CH O2NO2N O NaBH 4 methanol (82%) CH 2 OH O2NO2N HOH (84%) NaBH 4 ethanol Aldehyde Ketone

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

Examples: Lithium Aluminum Hydride Aldehyde Ketone O CH 3 (CH 2 ) 5 CH 1. LiAlH 4 diethyl ether 2. H 2 O O (C 6 H 5 ) 2 CHCCH 3 1. LiAlH 4 diethyl ether 2. H 2 O (84%) CH 3 (CH 2 ) 5 CH 2 OH (86%) OH (C 6 H 5 ) 2 CHCHCH 3

Neither NaBH 4 or LiAlH 4 reduces carbon-carbon double bonds. O HOH 1. LiAlH 4 diethyl ether 2. H 2 O (90%) Selectivity

Preparation of Alcohols By Reduction of Carboxylic Acids

lithium aluminum hydride is only effective reducing agent Reduction of Carboxylic Acids Gives Primary Alcohols C R HOHOH H C R HO O

Example: Reduction of a Carboxylic Acid 1. LiAlH 4 diethyl ether 2. H 2 O COH O CH 2 OH (78%)

Preparation of Alcohols From Epoxides

Reaction of Grignard Reagents with Epoxides H2CH2C CH 2 O RMgX CH 2 OMgX R H3O+H3O+ RCH 2 CH 2 OH

CH 3 (CH 2 ) 4 CH 2 MgBr H2CH2C CH 2 O + 1. diethyl ether 2. H 3 O + CH 3 (CH 2 ) 4 CH 2 CH 2 CH 2 OH (71%) Example

Preparation of Diols

Diols are Prepared by... Reactions used to prepare alcohols Hydroxylation of alkenes

O O HCCH 2 CHCH 2 CH CH 3 H 2 (100 atm) Ni, 125°C HOCH 2 CH 2 CHCH 2 CH 2 OH CH 3 3-Methyl-1,5-pentanediol (81-83%) Example: Reduction of a Dialdehyde

Vicinal diols have hydroxyl groups on adjacent carbons. Ethylene glycol (HOCH 2 CH 2 OH) is most familiar example. Hydroxylation of Alkenes Gives Vicinal Diols

Osmium Tetraoxide is Key Reagent C C HOHO OHOH C C OsO 4 O O Os OO C C Cyclic osmate ester

(CH 3 ) 3 COOH OsO 4 (cat) tert-Butyl alcohol HO – Example (73%) CH 2 CH 3 (CH 2 ) 7 CH CH 3 (CH 2 ) 7 CHCH 2 OH OHOH

Example H H (CH 3 ) 3 COOH OsO 4 (cat) tert-Butyl alcohol HO – (62%) H H OHOH HOHO Stereospecific syn addition of —OH groups to each carbon of double bond

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

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.

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

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

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