Post on 01-Apr-2015
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
diethyl etherdiethyl ether
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
diethyl etherdiethyl ether
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
diethyl etherdiethyl ether
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
diethyl etherdiethyl ether
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––
Example Example Example Example
(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––
Example Example Example Example
(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
Mechanism of Formation of Diethyl EtherMechanism of Formation of Diethyl Ether Mechanism of Formation of Diethyl EtherMechanism of Formation of Diethyl Ether
Step 2:Step 2:Step 2:Step 2:
CHCH33CHCH22••••
HH
HH
++OO
CHCH33CHCH22OO•••• ••••
HH
++++
CHCH33CHCH22
CHCH33CHCH22OO ••••
HH
••••
HH
HH
OO••••
Dr. Wolf's CHM 201 & 202 15-43
Mechanism of Formation of Diethyl EtherMechanism of Formation of Diethyl Ether Mechanism of Formation of Diethyl EtherMechanism of Formation of Diethyl Ether
Step 3:Step 3:Step 3:Step 3:
++++
CHCH33CHCH22
CHCH33CHCH22OO ••••
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
Enzyme-catalyzedEnzyme-catalyzedEnzyme-catalyzedEnzyme-catalyzed
CHCH33CCHH22OOHH ++
NN
HH
CNHCNH22
OO
++
RR
++HH++
Dr. Wolf's CHM 201 & 202 15-70
Enzyme-catalyzedEnzyme-catalyzedEnzyme-catalyzedEnzyme-catalyzed
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