Dr. Wolf's CHM 201 & 202 15-1 Chapter 15 Alcohols, Diols, and Thiols.

Dr. Wolf's CHM 201 & 202 15-1

Chapter 15Chapter 15Alcohols, Diols, and ThiolsAlcohols, Diols, and Thiols

Dr. Wolf's CHM 201 & 202 15-2

Sources of AlcoholsSources of Alcohols

Dr. Wolf's CHM 201 & 202 15-3

MethanolMethanol is an industrial chemical is an industrial chemical

end uses: solvent, antifreeze, fuelend uses: solvent, antifreeze, fuel

principal use: preparation of formaldehydeprincipal use: preparation of formaldehyde

MethanolMethanolMethanolMethanol

Dr. Wolf's CHM 201 & 202 15-4

MethanolMethanol is an industrial chemical is an industrial chemical

end uses: solvent, antifreeze, fuelend uses: solvent, antifreeze, fuel

principal use: preparation of formaldehydeprincipal use: preparation of formaldehyde

prepared by hydrogenation of carbon prepared by hydrogenation of carbon monoxidemonoxide

CO + 2HCO + 2H22 CH CH33OHOHCO + 2HCO + 2H22 CH CH33OHOH

MethanolMethanolMethanolMethanol

Dr. Wolf's CHM 201 & 202 15-5

EthanolEthanol is an industrial chemical is an industrial chemical

Most ethanol comes from fermentationMost ethanol comes from fermentation

Synthetic ethanol is produced by hydrationSynthetic ethanol is produced by hydrationof ethyleneof ethylene

Synthetic ethanol is denatured (madeSynthetic ethanol is denatured (madeunfit for drinking) by adding methanol, benzene,unfit for drinking) by adding methanol, benzene,pyridine, castor oil, gasoline, etc.pyridine, castor oil, gasoline, etc.

EthanolEthanolEthanolEthanol

Dr. Wolf's CHM 201 & 202 15-6

Isopropyl alcohol is Isopropyl alcohol is prepared by hydration of prepared by hydration of propene.propene.

All alcohols with four carbons or fewer are All alcohols with four carbons or fewer are readily available.readily available.

Most alcohols with five or six carbons are Most alcohols with five or six carbons are readily available.readily available.

Other alcoholsOther alcoholsOther alcoholsOther alcohols

Dr. Wolf's CHM 201 & 202 15-7

Hydration of alkenesHydration of alkenes

Hydroboration-oxidation of alkenesHydroboration-oxidation of alkenes

Hydrolysis of alkyl halidesHydrolysis of alkyl halides

Syntheses using Syntheses using Grignard reagentsGrignard reagentsorganolithium reagentsorganolithium reagents

Sources of alcoholsSources of alcoholsSources of alcoholsSources of alcohols

Reactions discussed in earlier chapters (Table 15.1)Reactions discussed in earlier chapters (Table 15.1)

Dr. Wolf's CHM 201 & 202 15-8

Reduction of aldehydes and ketonesReduction of aldehydes and ketones

Reduction of carboxylic acidsReduction of carboxylic acids

Reduction of estersReduction of esters

Reaction of Grignard reagents with epoxidesReaction of Grignard reagents with epoxides

Diols by hydroxylation of alkenesDiols by hydroxylation of alkenes

Sources of alcoholsSources of alcoholsSources of alcoholsSources of alcohols

New methods in Chapter 15New methods in Chapter 15

Dr. Wolf's CHM 201 & 202 15-9

Preparation of AlcoholsPreparation of Alcoholsbyby

Reduction of Aldehydes and KetonesReduction of Aldehydes and Ketones

Dr. Wolf's CHM 201 & 202 15-10

CC

RR

HH OHOH

HH

CC

RR

HH

OO

Reduction of Aldehydes Gives Primary AlcoholsReduction of Aldehydes Gives Primary AlcoholsReduction of Aldehydes Gives Primary AlcoholsReduction of Aldehydes Gives Primary Alcohols

Dr. Wolf's CHM 201 & 202 15-11

Pt, ethanolPt, ethanol

(92%)(92%)

Example: Catalytic HydrogenationExample: Catalytic HydrogenationExample: Catalytic HydrogenationExample: Catalytic Hydrogenation

CHCH33OO CHCH22OHOH

OO

CHCH33OO CHCH ++ HH22

Dr. Wolf's CHM 201 & 202 15-12

CC

RR

HH OHOH

R'R'

CC

RR

R'R'

OO

Reduction of Ketones Gives Secondary AlcoholsReduction of Ketones Gives Secondary AlcoholsReduction of Ketones Gives Secondary AlcoholsReduction of Ketones Gives Secondary Alcohols

Dr. Wolf's CHM 201 & 202 15-13

(93-95%)(93-95%)

Example: Catalytic HydrogenationExample: Catalytic HydrogenationExample: Catalytic HydrogenationExample: Catalytic Hydrogenation

++ HH22

OO PtPt

ethanolethanol

HH OHOH

Dr. Wolf's CHM 201 & 202 15-14

HH::––

HH::––

CC

RR

HH OOHH

HH

CC

RR

HH

OO

CC

RR

HH OOHH

R'R'

CC

RR

R'R'

OO

Retrosynthetic AnalysisRetrosynthetic AnalysisRetrosynthetic AnalysisRetrosynthetic Analysis

Dr. Wolf's CHM 201 & 202 15-15

SodiumSodiumborohydrideborohydride

LithiumLithiumaluminum hydridealuminum hydride

LiLi++

NaNa++ ––

BB

HH

HH

HHHH––

AlAl

HH

HH

HHHH

Metal Hydride Reducing AgentsMetal Hydride Reducing AgentsMetal Hydride Reducing AgentsMetal Hydride Reducing Agents

act as hydride donorsact as hydride donors

Dr. Wolf's CHM 201 & 202 15-16

NaBHNaBH44

(82%)(82%)

Examples: Sodium BorohydrideExamples: Sodium BorohydrideExamples: Sodium BorohydrideExamples: Sodium Borohydride

CHCH22OHOH

OO

CHCH

OO22NN methanolmethanol

OO22NN OO

HH OHOH

(84%)(84%)

NaBHNaBH44

ethanolethanol

AldehydeAldehyde

KetoneKetone

Dr. Wolf's CHM 201 & 202 15-17

Lithium aluminum hydrideLithium aluminum hydrideLithium aluminum hydrideLithium aluminum hydride

more reactive than sodium borohydridemore reactive than sodium borohydride

cannot use water, ethanol, methanol etc.cannot use water, ethanol, methanol etc.as solventsas solvents

diethyl ether is most commonly used solventdiethyl ether is most commonly used solvent

Dr. Wolf's CHM 201 & 202 15-18

Examples: Lithium Aluminum HydrideExamples: Lithium Aluminum HydrideExamples: Lithium Aluminum HydrideExamples: Lithium Aluminum Hydride

(84%)(84%)

AldehydeAldehyde

KetoneKetone

OO

CHCH33(CH(CH22))55CHCH CHCH33(CH(CH22))55CHCH22OHOH

1. LiAlH1. LiAlH44

diethyl etherdiethyl ether

2. H2. H22OO

OO

(C(C66HH55))22CHCCHCHCCH33

1. LiAlH1. LiAlH44


2. H2. H22OO

(86%)(86%)

OHOH

(C(C66HH55))22CHCHCHCHCHCH33

Dr. Wolf's CHM 201 & 202 15-19

neither NaBHneither NaBH44 or LiAlH or LiAlH44

reduces isolatedreduces isolateddouble bondsdouble bonds

HH OHOH

OO

1. LiAlH1. LiAlH44


2. H2. H22OO

(90%)(90%)

SelectivitySelectivitySelectivitySelectivity

Dr. Wolf's CHM 201 & 202 15-20

Preparation of Alcohols By ReductionPreparation of Alcohols By Reductionof Carboxylic Acids and Estersof Carboxylic Acids and Esters

Dr. Wolf's CHM 201 & 202 15-21

lithium aluminum hydride is only lithium aluminum hydride is only effective reducing agenteffective reducing agent

Reduction of Carboxylic AcidsReduction of Carboxylic AcidsGives Primary AlcoholsGives Primary Alcohols

Reduction of Carboxylic AcidsReduction of Carboxylic AcidsGives Primary AlcoholsGives Primary Alcohols

CC

RR

HH OHOH

HH

CC

RR

HOHO

OO

Dr. Wolf's CHM 201 & 202 15-22

Example: Reduction of a Carboxylic AcidExample: Reduction of a Carboxylic AcidExample: Reduction of a Carboxylic AcidExample: Reduction of a Carboxylic Acid

1. LiAlH1. LiAlH44


2. H2. H22OO

COHCOH

OO CHCH22OHOH

(78%)(78%)

Dr. Wolf's CHM 201 & 202 15-23

Lithium aluminum hydride preferred forLithium aluminum hydride preferred forlaboratory reductionslaboratory reductions

Sodium borohydride reduction is too slowSodium borohydride reduction is too slowto be usefulto be useful

Catalytic hydrogenolysis used in industryCatalytic hydrogenolysis used in industrybut conditions difficult or dangerous to duplicate but conditions difficult or dangerous to duplicate in the laboratory (special catalyst, highin the laboratory (special catalyst, hightemperature, high pressuretemperature, high pressure

Reduction of EstersReduction of EstersGives Primary AlcoholsGives Primary Alcohols

(Also Chapter 19)(Also Chapter 19)

Reduction of EstersReduction of EstersGives Primary AlcoholsGives Primary Alcohols

(Also Chapter 19)(Also Chapter 19)

Dr. Wolf's CHM 201 & 202 15-24

Example: Reduction of an EsterExample: Reduction of an EsterExample: Reduction of an EsterExample: Reduction of an Ester

1. LiAlH1. LiAlH44


2. H2. H22OO

(90%)(90%)

OO

COCHCOCH22CHCH33

CHCH33CHCH22OHOH

CHCH22OHOH ++

Dr. Wolf's CHM 201 & 202 15-25

Preparation of Alcohols From EpoxidesPreparation of Alcohols From Epoxides

Dr. Wolf's CHM 201 & 202 15-26

Reaction of Grignard ReagentsReaction of Grignard Reagentswith Epoxideswith Epoxides

Reaction of Grignard ReagentsReaction of Grignard Reagentswith Epoxideswith Epoxides

CHCH22 CHCH22 OMgXOMgX

HH33OO++

HH22CC CHCH22

OO

RR MgXMgX RR

RRCHCH22CHCH22OHOH

Dr. Wolf's CHM 201 & 202 15-27

CHCH33(CH(CH22))44CHCH22MgBrMgBr HH22CC CHCH22

OO

++

1. diethyl ether1. diethyl ether2. H2. H33OO++

CHCH33(CH(CH22))44CHCH22CHCH22CHCH22OOHH

(71%)(71%)

Example Example Example Example

Dr. Wolf's CHM 201 & 202 15-28

Preparation of DiolsPreparation of Diols

Dr. Wolf's CHM 201 & 202 15-29

Diols are prepared by...Diols are prepared by...Diols are prepared by...Diols are prepared by...

reactions used to prepare alcoholsreactions used to prepare alcohols

hydroxylation of alkeneshydroxylation of alkenes

Dr. Wolf's CHM 201 & 202 15-30

OO OO

HCHCCHCH22CHCHCHCH22CH CH

CHCH33

HH22 (100 atm) (100 atm)

Ni, 125°CNi, 125°C

HOCHHOCH22CHCH22CHCHCHCH22CHCH22OHOH

CHCH33

3-Methyl-1,5-pentanediol3-Methyl-1,5-pentanediol

(81-83%)(81-83%)

Example: reduction of a dialdehydeExample: reduction of a dialdehydeExample: reduction of a dialdehydeExample: reduction of a dialdehyde

Dr. Wolf's CHM 201 & 202 15-31

vicinal diols have hydroxyl groups on adjacent vicinal diols have hydroxyl groups on adjacent carbonscarbons

ethylene glycol (HOCHethylene glycol (HOCH22CHCH22OH) is most familiar OH) is most familiar

exampleexample

Hydroxylation of AlkenesHydroxylation of AlkenesGives Vicinal DiolsGives Vicinal Diols

Hydroxylation of AlkenesHydroxylation of AlkenesGives Vicinal DiolsGives Vicinal Diols

Dr. Wolf's CHM 201 & 202 15-32

syn addition of —OH groups to each carbonsyn addition of —OH groups to each carbonof double bondof double bond

Osmium Tetraoxide is Key ReagentOsmium Tetraoxide is Key ReagentOsmium Tetraoxide is Key ReagentOsmium Tetraoxide is Key Reagent

CC CCHHOO OOHH

CC CC

OO OO

OsOs

OOOO

CCCC

Dr. Wolf's CHM 201 & 202 15-33

(CH(CH33))33COOHCOOHOsOOsO44 (cat) (cat)

tert-tert-Butyl alcoholButyl alcoholHOHO––


(73%)(73%)

CHCH22CHCH33(CH(CH22))77CHCH

CHCH33(CH(CH22))77CHCHCHCH22OHOH

OHOH

Dr. Wolf's CHM 201 & 202 15-34

(CH(CH33))33COOHCOOHOsOOsO44 (cat) (cat)

tert-tert-Butyl alcoholButyl alcoholHOHO––


(62%)(62%)

HH

HH

HH

HH

OHOHHOHO

Dr. Wolf's CHM 201 & 202 15-35

Reactions of Alcohols:A Review and a Preview

Dr. Wolf's CHM 201 & 202 15-36

Table 15.2 Review of Reactions of AlcoholsTable 15.2 Review of Reactions of AlcoholsTable 15.2 Review of Reactions of AlcoholsTable 15.2 Review of Reactions of Alcohols

reaction with hydrogen halides reaction with hydrogen halides

reaction with thionyl chloridereaction with thionyl chloride

reaction with phosphorous tribromidereaction with phosphorous tribromide

acid-catalyzed dehydrationacid-catalyzed dehydration

conversion to conversion to pp-toluenesulfonate -toluenesulfonate estersesters

Dr. Wolf's CHM 201 & 202 15-37

New Reactions of Alcohols in This ChapterNew Reactions of Alcohols in This ChapterNew Reactions of Alcohols in This ChapterNew Reactions of Alcohols in This Chapter

conversion to ethersconversion to ethers

esterificationesterification

esters of inorganic acidsesters of inorganic acids

oxidationoxidation

cleavage of vicinal diolscleavage of vicinal diols

Dr. Wolf's CHM 201 & 202 15-38

Conversion of Alcohols to Ethers

Dr. Wolf's CHM 201 & 202 15-39

RCHRCH22OO

HH

CHCH22RR

OHOH

HH++

RCHRCH22OO CHCH22RR HH OHOH++

Conversion of Alcohols to EthersConversion of Alcohols to EthersConversion of Alcohols to EthersConversion of Alcohols to Ethers

acid-catalyzedacid-catalyzed

referred to as a "condensation"referred to as a "condensation"

equilibrium; most favorable for primary alcoholsequilibrium; most favorable for primary alcohols

Dr. Wolf's CHM 201 & 202 15-40

ExampleExampleExampleExample

2CH2CH33CHCH22CHCH22CHCH22OHOH

HH22SOSO44, 130°C, 130°C

CHCH33CHCH22CHCH22CHCH22OCHOCH22CHCH22CHCH22CHCH33

(60%)(60%)

Dr. Wolf's CHM 201 & 202 15-41

Mechanism of Formation of Diethyl EtherMechanism of Formation of Diethyl Ether Mechanism of Formation of Diethyl EtherMechanism of Formation of Diethyl Ether

Step 1:Step 1:Step 1:Step 1:

CHCH33CHCH22OO•••• ••••

HH

HH OSOOSO22OHOH

CHCH33CHCH22OO ••••

HH

OSOOSO22OHOHHH

++––++

Dr. Wolf's CHM 201 & 202 15-42



CHCH33CHCH22••••

HH

HH

++OO

CHCH33CHCH22OO•••• ••••

HH

++++

CHCH33CHCH22


HH

••••

HH

HH

OO••••

Dr. Wolf's CHM 201 & 202 15-43



++++

CHCH33CHCH22


HH

OSOOSO22OHOH–– ••••••••

••••

HH OSOOSO22OHOH

••••

••••

CHCH33CHCH22

CHCH33CHCH22OO ••••••••

Dr. Wolf's CHM 201 & 202 15-44

reaction normally works wellreaction normally works wellonly for 5- and 6-memberedonly for 5- and 6-memberedringsrings

Intramolecular AnalogIntramolecular AnalogIntramolecular AnalogIntramolecular Analog

HOCHHOCH22CHCH22CHCH22CHCH22CHCH22OHOH

HH22SOSO44 130°130° OO

(76%)(76%)

Dr. Wolf's CHM 201 & 202 15-45

Intramolecular AnalogIntramolecular AnalogIntramolecular AnalogIntramolecular Analog

HOCHHOCH22CHCH22CHCH22CHCH22CHCH22OHOH

HH22SOSO44 130°130° OO

(76%)(76%)

via:via: OO

HH

++OO

HH

HH

••••

••••

••••

Dr. Wolf's CHM 201 & 202 15-46

Esterification

(more on esters and other acid derivatives in later

chapters)

Dr. Wolf's CHM 201 & 202 15-47

a condensation reactiona condensation reaction

called Fischer esterificationcalled Fischer esterification

acid catalyzedacid catalyzed

reversiblereversible

EsterificationEsterificationEsterificationEsterification

ROROHH HH22OO++

HH++

++R'COHR'COH

OO

R'CR'COROR

OO

Dr. Wolf's CHM 201 & 202 15-48

Example of Fischer EsterificationExample of Fischer EsterificationExample of Fischer EsterificationExample of Fischer Esterification

HH22OO++

CHCH33OHOH++COHCOH

OO COCHCOCH33

OO HH22SOSO44

0.1 mol0.1 mol 0.6 mol (i.e. excess)0.6 mol (i.e. excess)

70% yield based on benzoic acid70% yield based on benzoic acid

Dr. Wolf's CHM 201 & 202 15-49

high yieldshigh yields

not reversible when carried outnot reversible when carried outin presence of pyridinein presence of pyridine

Reaction of Alcohols with Acyl ChloridesReaction of Alcohols with Acyl ChloridesReaction of Alcohols with Acyl ChloridesReaction of Alcohols with Acyl Chlorides

ROROHH HClHCl++ ++R'CClR'CCl

OO

R'CR'COROR

OO

Dr. Wolf's CHM 201 & 202 15-50

pyridinepyridine

++ CClCClOO22NN

OOCHCH33CHCH22

CHCH33

OOHH

(63%)(63%)

NONO22

CHCH33CHCH22

CHCH33

OOCC

OO ExampleExampleExampleExample

Dr. Wolf's CHM 201 & 202 15-51

analogous to reaction with acyl analogous to reaction with acyl chlorideschlorides

Reaction of Alcohols with Acid AnhydridesReaction of Alcohols with Acid AnhydridesReaction of Alcohols with Acid AnhydridesReaction of Alcohols with Acid Anhydrides

ROROHH ++ ++R'CR'COROR

OOOO

R'COCR'R'COCR'

OO

R'COHR'COH

OO

Dr. Wolf's CHM 201 & 202 15-52

pyridinepyridine

(83%)(83%)

++CC66HH55CHCH22CHCH22OHOH

OO

FF33CCOCCFCCOCCF33

OO

CC66HH55CHCH22CHCH22OCCFOCCF33

OO

ExampleExampleExampleExample

Dr. Wolf's CHM 201 & 202 15-53

Esters of Inorganic Acids

Dr. Wolf's CHM 201 & 202 15-54

Esters of Inorganic AcidsEsters of Inorganic AcidsEsters of Inorganic AcidsEsters of Inorganic Acids

ROROH + HOH + HOEWGEWG ROROEWGEWG + H + H22OO

EWGEWG is an electron-withdrawing group is an electron-withdrawing group

HONOHONO22 (HO)(HO)22SOSO22 (HO)(HO)33PP OO++ ––

Dr. Wolf's CHM 201 & 202 15-55

Esters of Inorganic AcidsEsters of Inorganic AcidsEsters of Inorganic AcidsEsters of Inorganic Acids

ROROH + HOH + HOEWGEWG ROROEWGEWG + H + H22OO

EWGEWG is an electron-withdrawing group is an electron-withdrawing group

HOHONONO22 (HO)(HO)22SOSO22 (HO)(HO)33PP OO++ ––

CHCH33OOH + HOH + HONONO22 CHCH33OONONO22 + H + H22OO

(66-80%)(66-80%)

Dr. Wolf's CHM 201 & 202 15-56

Oxidation of Alcohols

Dr. Wolf's CHM 201 & 202 15-57

Primary alcoholsPrimary alcohols

Secondary alcoholsSecondary alcohols

from Hfrom H22OO

Oxidation of AlcoholsOxidation of AlcoholsOxidation of AlcoholsOxidation of Alcohols

RCHRCH22OHOH

OO

RCHRCH

OO

RCOHRCOH

OO

RCR'RCR'RCHR'RCHR'

OHOH

Dr. Wolf's CHM 201 & 202 15-58

Aqueous solutionAqueous solution

Mn(VII) Mn(VII) Cr(VI)Cr(VI)

KMnOKMnO44 HH22CrOCrO44

HH22CrCr22OO77

Typical Oxidizing AgentsTypical Oxidizing AgentsTypical Oxidizing AgentsTypical Oxidizing Agents

Dr. Wolf's CHM 201 & 202 15-59

Aqueous Cr(VI)Aqueous Cr(VI)Aqueous Cr(VI)Aqueous Cr(VI)

FCHFCH22CHCH22CHCH22CHCH22OHOH

KK22CrCr22OO77

HH22SOSO44

HH22OO

FCHFCH22CHCH22CHCH22COHCOH

(74%)(74%)

OO

Dr. Wolf's CHM 201 & 202 15-60

Aqueous Cr(VI)Aqueous Cr(VI)Aqueous Cr(VI)Aqueous Cr(VI)

FCHFCH22CHCH22CHCH22CHCH22OHOH

KK22CrCr22OO77

HH22SOSO44

HH22OO

FCHFCH22CHCH22CHCH22COHCOH

(74%)(74%)

OO

NaNa22CrCr22OO77

HH22SOSO44

HH22OO

(85%)(85%)

HH

OHOH OO

Dr. Wolf's CHM 201 & 202 15-61

All are used in CHAll are used in CH22ClCl22

Pyridinium dichromate (PDC)Pyridinium dichromate (PDC)

(C(C55HH55NHNH++))2 2 CrCr22OO77

2–2–

Pyridinium chlorochromate (PCC)Pyridinium chlorochromate (PCC)

CC55HH55NHNH++ ClCrO ClCrO33––

Nonaqueous Sources of Cr(VI)Nonaqueous Sources of Cr(VI)Nonaqueous Sources of Cr(VI)Nonaqueous Sources of Cr(VI)

Dr. Wolf's CHM 201 & 202 15-62

Example: Oxidation of Example: Oxidation of a primary alcohol with a primary alcohol with PCCPCC(pyridinium chlorochromate)(pyridinium chlorochromate)

Example: Oxidation of Example: Oxidation of a primary alcohol with a primary alcohol with PCCPCC(pyridinium chlorochromate)(pyridinium chlorochromate)

CHCH33(CH(CH22))55CHCH22OHOHPCCPCC

CHCH22ClCl22

OO

CHCH33(CH(CH22))55CHCH

(78%)(78%)

ClCrOClCrO33––

NN

HH

++

Dr. Wolf's CHM 201 & 202 15-63

PDCPDC CHCH22ClCl22

OO

(94%)(94%)

CHCH22OHOH(CH(CH33))33CC CHCH(CH(CH33))33CC

Example: Oxidation of Example: Oxidation of a primary alcohol with a primary alcohol with PDCPDC

(pryidinium dichromate)(pryidinium dichromate)

Example: Oxidation of Example: Oxidation of a primary alcohol with a primary alcohol with PDCPDC

(pryidinium dichromate)(pryidinium dichromate)

Dr. Wolf's CHM 201 & 202 15-64

MechanismMechanismMechanismMechanism

involves formation involves formation and elimination of and elimination of a chromate estera chromate ester

CC

OOHH

HOHOCrOHCrOH

OO

OO

CC

OO

HH HHOO

OO

CrOHCrOH

Dr. Wolf's CHM 201 & 202 15-65

MechanismMechanismMechanismMechanism

involves formation involves formation and elimination of and elimination of a chromate estera chromate ester

CC

OOHH

HOHOCrOHCrOH

OO

OO

CC

OO

HH HHOO

OO

CrOHCrOH

OO••••

••••

CC OO

HH HH

Dr. Wolf's CHM 201 & 202 15-66

Biological Oxidation of Alcohols

Dr. Wolf's CHM 201 & 202 15-67

alcohol alcohol dehydrogenasedehydrogenase

Enzyme-catalyzedEnzyme-catalyzedEnzyme-catalyzedEnzyme-catalyzed

CHCH33CCHH22OOHH ++ NAD (a coenzyme)NAD (a coenzyme)++

++ ++ ++HHNADNAD HHCHCH33CCHH OO

Dr. Wolf's CHM 201 & 202 15-68

nicotinamide adenine dinucleotide (oxidized form)nicotinamide adenine dinucleotide (oxidized form)

HOHO

HOHO

OOOO

NN

NN

NHNH22

PPOO

PPOO

OO

HOHOOHOH

HH

CC

OO

NHNH22NN

OO OO OO OO

++

____

Figure 15.3 Structure of NADFigure 15.3 Structure of NAD++Figure 15.3 Structure of NADFigure 15.3 Structure of NAD++

Dr. Wolf's CHM 201 & 202 15-69


CHCH33CCHH22OOHH ++

NN

HH

CNHCNH22

OO

++

RR

++HH++

Dr. Wolf's CHM 201 & 202 15-70


NN

HH

CNHCNH22

OO

RR

CHCH33CCHH

OOHH

••••

Dr. Wolf's CHM 201 & 202 15-71

Oxidative Cleavage of Vicinal DiolsOxidative Cleavage of Vicinal Diols

Dr. Wolf's CHM 201 & 202 15-72

Cleavage of Vicinal Diols by Periodic AcidCleavage of Vicinal Diols by Periodic AcidCleavage of Vicinal Diols by Periodic AcidCleavage of Vicinal Diols by Periodic Acid

CCCC

HOHO OHOH

HIOHIO44CC OO OO CC++

Dr. Wolf's CHM 201 & 202 15-73

Cleavage of Vicinal Diols by Periodic AcidCleavage of Vicinal Diols by Periodic AcidCleavage of Vicinal Diols by Periodic AcidCleavage of Vicinal Diols by Periodic Acid

HIOHIO44

CHCH CCHCCH33

CHCH33

OHOHHOHO

CHCH33CCHCCH33

OO CHCH

OO

++

(83%)(83%)

Dr. Wolf's CHM 201 & 202 15-74

Cyclic Diols are CleavedCyclic Diols are CleavedCyclic Diols are CleavedCyclic Diols are Cleaved

HIOHIO44

OHOH

OHOH

OO

HCCHHCCH22CHCH22CHCH22CHCH

OO

Dr. Wolf's CHM 201 & 202 15-75

Preparation of ThiolsPreparation of Thiols

Dr. Wolf's CHM 201 & 202 15-76

Nomenclature of ThiolsNomenclature of ThiolsNomenclature of ThiolsNomenclature of Thiols

1) analogous to alcohols, but suffix is -1) analogous to alcohols, but suffix is -thiol thiol rather than -rather than -olol

2) 2) final -final -ee of alkane name is retained, not of alkane name is retained, not dropped as with alcoholsdropped as with alcohols

Dr. Wolf's CHM 201 & 202 15-77

Nomenclature of ThiolsNomenclature of ThiolsNomenclature of ThiolsNomenclature of Thiols

1) analogous to alcohols, but suffix is -1) analogous to alcohols, but suffix is -thiol thiol rather than -rather than -olol

2) 2) final -final -ee of alkane name is retained, not of alkane name is retained, not dropped as with alcoholsdropped as with alcohols

CHCH33CHCHCHCH22CHCH22SHSH

CHCH33

3-Methyl-1-butanethiol3-Methyl-1-butanethiol

Dr. Wolf's CHM 201 & 202 15-82

1. low molecular weight thiols have foul odors1. low molecular weight thiols have foul odors

2. hydrogen bonding is much weaker in thiols 2. hydrogen bonding is much weaker in thiols than than in alcoholsin alcohols

3. thiols are stronger acids than alcohols3. thiols are stronger acids than alcohols

4. thiols are more easily oxidized than alcohols; 4. thiols are more easily oxidized than alcohols; oxidation takes place at sulfuroxidation takes place at sulfur

Properties of ThiolsProperties of ThiolsProperties of ThiolsProperties of Thiols

Thiols are less polar than alcoholsThiols are less polar than alcohols

MethanolMethanol MethanethiolMethanethiol

bp: 65°Cbp: 65°C bp: 6°Cbp: 6°C

Dr. Wolf's CHM 201 & 202 15-83

have phave pKKaas of about 10; can be s of about 10; can be deprotonated in deprotonated in aqueous baseaqueous base

stronger acidstronger acid(p(pKKaa = 10) = 10)

weaker acidweaker acid(p(pKKaa = 15.7) = 15.7)

Thiols are stronger acids than alcoholsThiols are stronger acids than alcoholsThiols are stronger acids than alcoholsThiols are stronger acids than alcohols

HHRSRS••••

••••

••••

••••OOHH••••

––RSRS

••••

••••HH

••••

••••OOHH••••

––++++

RSRS–– and HS and HS –– are weakly basic and good nucleophiles are weakly basic and good nucleophiles HH ClCl HHCC66HH55SS

CC66HH55SNaSNa

SSNN22(75%)(75%)

KSHKSH

SSNN22

(67%)(67%)

BrBr

SHSH

Dr. Wolf's CHM 201 & 202 15-84

Oxidation of thiols take place at sulfurOxidation of thiols take place at sulfurOxidation of thiols take place at sulfurOxidation of thiols take place at sulfur

thiol (reduced)thiol (reduced) disulfide (oxidized)disulfide (oxidized)

RSRS••••

••••HH RSRS

••••

••••SRSR••••

••••

thiol-disulfide redox pair is important in thiol-disulfide redox pair is important in biochemistrybiochemistry

other oxidative processes place 1, 2, or 3 other oxidative processes place 1, 2, or 3 oxygen atoms on sulfuroxygen atoms on sulfur

Dr. Wolf's CHM 201 & 202 15-85

Oxidation of thiols take place at sulfurOxidation of thiols take place at sulfurOxidation of thiols take place at sulfurOxidation of thiols take place at sulfur

thiolthiol disulfidedisulfide

sulfinic acidsulfinic acidsulfonic acidsulfonic acid

RSRS••••

••••HH RSRS

••••

••••SRSR••••

••••

sulfenic acidsulfenic acid

RSRS••••

••••OHOH RSRS

••••

••••OHOH

OO•••• ••••––

++RSRS

••••

OHOH

OO•••• ••••––

2+2+

••••OO•••• ••••

––

Dr. Wolf's CHM 201 & 202 15-86

HHSSCHCH22CHCH22CH(CHCH(CH22))44COHCOH

SSHH

OO22, FeCl, FeCl33

(CH(CH22))44COHCOH -Lipoic acid (78%)-Lipoic acid (78%)

Example: sulfide-disulfide redox pairExample: sulfide-disulfide redox pairExample: sulfide-disulfide redox pairExample: sulfide-disulfide redox pair

OO

OOSS SS

Dr. Wolf's CHM 201 & 202 15-87

Spectroscopic Analysis of AlcoholsSpectroscopic Analysis of Alcohols

Dr. Wolf's CHM 201 & 202 15-88

O—H stretching: 3200-3650 cmO—H stretching: 3200-3650 cm–1 –1 (broad) (broad)

C—O stretching: 1025-1200 cmC—O stretching: 1025-1200 cm–1 –1 (broad) (broad)

Infrared SpectroscopyInfrared SpectroscopyInfrared SpectroscopyInfrared Spectroscopy

Dr. Wolf's CHM 201 & 202 15-89

2000200035003500 30003000 25002500 1000100015001500 500500

Wave number, cmWave number, cm-1-1

Figure 15.4: Infrared Spectrum of CyclohexanolFigure 15.4: Infrared Spectrum of CyclohexanolFigure 15.4: Infrared Spectrum of CyclohexanolFigure 15.4: Infrared Spectrum of Cyclohexanol

O—HO—H

C—HC—H

C—OC—O

OHOH

Dr. Wolf's CHM 201 & 202 15-90

chemical shift of O—H proton is variable; chemical shift of O—H proton is variable; depends on temperature and concentrationdepends on temperature and concentration

O—H proton can be identified by adding DO—H proton can be identified by adding D22O; O; signal for O—H disappears (converted to O—D)signal for O—H disappears (converted to O—D)

11H NMRH NMR11H NMRH NMR

CC OOHH HH

3.3-4 ppm3.3-4 ppm 0.5-5 ppm0.5-5 ppm

Dr. Wolf's CHM 201 & 202 15-91

01.02.03.04.05.06.07.08.09.010.0

Chemical shift (Chemical shift (, ppm), ppm)

Figure 15.5 (page 607)Figure 15.5 (page 607) CCHH22CCHH22OOHH

Dr. Wolf's CHM 201 & 202 15-92

chemical shift of chemical shift of CC—OH is —OH is 60-75 ppm 60-75 ppm

CC—O is about 35-50 ppm less shielded than —O is about 35-50 ppm less shielded than CC—H—H

1313C NMRC NMR1313C NMRC NMR

CHCH33CHCH22CHCH22CCHH33 CHCH33CHCH22CHCH22CCHH22OOHH

13 ppm13 ppm 61.4 ppm61.4 ppm

Dr. Wolf's CHM 201 & 202 15-93

UV-VISUV-VISUV-VISUV-VIS

Unless there are other chromophores in theUnless there are other chromophores in themolecule, alcohols are transparent abovemolecule, alcohols are transparent aboveabout 200 nm; about 200 nm; maxmax for methanol, for example, is 177 nm. for methanol, for example, is 177 nm.

Dr. Wolf's CHM 201 & 202 15-94

molecular ion peak is usually molecular ion peak is usually smallsmall

a peak corresponding to loss of a peak corresponding to loss of HH22OOfrom the molecular ion (M - 18) isfrom the molecular ion (M - 18) isusually presentusually present

peak corresponding to loss of anpeak corresponding to loss of analkyl group to give an oxygen-alkyl group to give an oxygen-stabilized carbocation is usuallystabilized carbocation is usuallyprominentprominent

Mass Spectrometry of AlcoholsMass Spectrometry of AlcoholsMass Spectrometry of AlcoholsMass Spectrometry of Alcohols

Dr. Wolf's CHM 201 & 202 15-95

molecular ion peak is usually molecular ion peak is usually smallsmall

a peak corresponding to loss of a peak corresponding to loss of HH22OOfrom the molecular ion (M - 18) isfrom the molecular ion (M - 18) isusually presentusually present

peak corresponding to loss of anpeak corresponding to loss of analkyl group to give an oxygen-alkyl group to give an oxygen-stabilized carbocation is usuallystabilized carbocation is usuallyprominentprominent

Mass Spectrometry of AlcoholsMass Spectrometry of AlcoholsMass Spectrometry of AlcoholsMass Spectrometry of Alcohols

CHCH22RR OHOH••••

••••

CHCH22RR OHOH••++

••••

CHCH22 OHOHRR ••••••

++

End of Chapter 15

Dr. Wolf's CHM 201 & 202 15-1 Chapter 15 Alcohols, Diols, and Thiols.

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Transcript of Dr. Wolf's CHM 201 & 202 15-1 Chapter 15 Alcohols, Diols, and Thiols.