Dr. Wolf's CHM 201 & Chapter 15 Alcohols, Diols, and Thiols

Dr. Wolf's CHM 201 & Sources of Alcohols

Dr. Wolf's CHM 201 & Methanol is an industrial chemical end uses: solvent, antifreeze, fuel principal use: preparation of formaldehyde MethanolMethanol

Dr. Wolf's CHM 201 & Methanol is an industrial chemical end uses: solvent, antifreeze, fuel principal use: preparation of formaldehyde prepared by hydrogenation of carbon monoxide CO + 2H 2  CH 3 OH MethanolMethanol

Dr. Wolf's CHM 201 & Ethanol is an industrial chemical Most ethanol comes from fermentation Synthetic ethanol is produced by hydration of ethylene Synthetic ethanol is denatured (made unfit for drinking) by adding methanol, benzene, pyridine, castor oil, gasoline, etc. EthanolEthanol

Dr. Wolf's CHM 201 & Isopropyl alcohol is prepared by hydration of propene. All alcohols with four carbons or fewer are readily available. Most alcohols with five or six carbons are readily available. Other alcohols

Dr. Wolf's CHM 201 & 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)

Dr. Wolf's CHM 201 & Reduction of aldehydes and ketones Reduction of carboxylic acids Reduction of esters Reaction of Grignard reagents with epoxides Diols by hydroxylation of alkenes Sources of alcohols New methods in Chapter 15

Dr. Wolf's CHM 201 & Preparation of Alcohols by Reduction of Aldehydes and Ketones

Dr. Wolf's CHM 201 & CRHOH H CRH O Reduction of Aldehydes Gives Primary Alcohols

Dr. Wolf's CHM 201 & Pt, ethanol (92%) Example: Catalytic Hydrogenation CH 3 O CH 2 OH O CH 3 O CH + H2H2H2H2

Dr. Wolf's CHM 201 & CRHOH R' C R R' O Reduction of Ketones Gives Secondary Alcohols

Dr. Wolf's CHM 201 & (93-95%) Example: Catalytic Hydrogenation + H2H2H2H2OPt ethanol HOH

Dr. Wolf's CHM 201 & H:–H:–H:–H:– H:–H:–H:–H:– CRH OHOHOHOH H CRH O CRH OHOHOHOH R' CRR' O Retrosynthetic Analysis

Dr. Wolf's CHM 201 & Sodium borohydride Lithium aluminum hydride Li+ Na+ – B HHHH – Al HHHH Metal Hydride Reducing Agents act as hydride donors

Dr. Wolf's CHM 201 & NaBH 4 (82%) Examples: Sodium Borohydride CH 2 OH O CH O2NO2NO2NO2Nmethanol O2NO2NO2NO2N O HOH(84%) NaBH 4 ethanol Aldehyde Ketone

Dr. Wolf's CHM 201 & Lithium aluminum hydride more reactive than sodium borohydride cannot use water, ethanol, methanol etc. as solvents diethyl ether is most commonly used solvent

Dr. Wolf's CHM 201 & Examples: Lithium Aluminum Hydride (84%) Aldehyde KetoneO CH 3 (CH 2 ) 5 CH CH 3 (CH 2 ) 5 CH 2 OH 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 (86%)OH (C 6 H 5 ) 2 CHCHCH 3

Dr. Wolf's CHM 201 & neither NaBH 4 or LiAlH 4 reduces isolated double bonds HOH O 1. LiAlH 4 diethyl ether 2. H 2 O (90%) SelectivitySelectivity

Dr. Wolf's CHM 201 & Preparation of Alcohols By Reduction of Carboxylic Acids and Esters

Dr. Wolf's CHM 201 & lithium aluminum hydride is only effective reducing agent Reduction of Carboxylic Acids Gives Primary Alcohols CRHOH H C R HO O

Dr. Wolf's CHM 201 & Example: Reduction of a Carboxylic Acid 1. LiAlH 4 diethyl ether 2. H 2 O COH O CH 2 OH (78%)

Dr. Wolf's CHM 201 & Lithium aluminum hydride preferred for laboratory reductions Sodium borohydride reduction is too slow to be useful Catalytic hydrogenolysis used in industry but conditions difficult or dangerous to duplicate in the laboratory (special catalyst, high temperature, high pressure Reduction of Esters Gives Primary Alcohols

Dr. Wolf's CHM 201 & Example: Reduction of an Ester 1. LiAlH 4 diethyl ether 2. H 2 O (90%)O COCH 2 CH 3 CH 3 CH 2 OH CH 2 OH +

Dr. Wolf's CHM 201 & Preparation of Alcohols From Epoxides

Dr. Wolf's CHM 201 & Reaction of Grignard Reagents with Epoxides CH 2 OMgX H3O+H3O+H3O+H3O+ H2CH2CH2CH2C O RMgXR RCH 2 CH 2 OH

Dr. Wolf's CHM 201 & CH 3 (CH 2 ) 4 CH 2 MgBr H2CH2CH2CH2C CH 2 O + 1. diethyl ether 2. H 3 O + CH 3 (CH 2 ) 4 CH 2 CH 2 CH 2 OH (71%) ExampleExample

Dr. Wolf's CHM 201 & Preparation of Diols

Dr. Wolf's CHM 201 & Diols are prepared by... reactions used to prepare alcohols hydroxylation of alkenes

Dr. Wolf's CHM 201 & OO 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

Dr. Wolf's CHM 201 & 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

Dr. Wolf's CHM 201 & syn addition of —OH groups to each carbon of double bond Osmium Tetraoxide is Key Reagent C C HOHOHOHO OHOHOHOH C C O O Os OO C C

Dr. Wolf's CHM 201 & (CH 3 ) 3 COOH OsO 4 (cat) tert-Butyl alcohol HO – ExampleExample (73%) CH 2 CH 3 (CH 2 ) 7 CH CH 3 (CH 2 ) 7 CHCH 2 OH OH

Dr. Wolf's CHM 201 & (CH 3 ) 3 COOH OsO 4 (cat) tert-Butyl alcohol HO – ExampleExample (62%)HH HH OH HO

Dr. Wolf's CHM 201 & Reactions of Alcohols: A Review and a Preview

Dr. Wolf's CHM 201 & 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

Dr. Wolf's CHM 201 & New Reactions of Alcohols in This Chapter conversion to ethers esterification esters of inorganic acids oxidation cleavage of vicinal diols

Dr. Wolf's CHM 201 & Conversion of Alcohols to Ethers

Dr. Wolf's CHM 201 & 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

Dr. Wolf's CHM 201 & ExampleExample 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%)

Dr. Wolf's CHM 201 & Mechanism of Formation of Diethyl Ether 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 + – +

Dr. Wolf's CHM 201 & Mechanism of Formation of Diethyl Ether 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

Dr. Wolf's CHM 201 & Mechanism of Formation of Diethyl Ether 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

Dr. Wolf's CHM 201 & 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%)

Dr. Wolf's CHM 201 & 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