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Chapter 15
Alcohols, Diols, and Thiols
Dr. Wolf's CHM 201 & 202
15-1
Sources of Alcohols
Dr. Wolf's CHM 201 & 202
15-2
Methanol
Methanol is an industrial chemical
end uses: solvent, antifreeze, fuel
principal use: preparation of formaldehyde
Dr. Wolf's CHM 201 & 202
15-3
Methanol
Methanol is an industrial chemical
end uses: solvent, antifreeze, fuel
principal use: preparation of formaldehyde
prepared by hydrogenation of carbon
monoxide
CO + 2H2  CH3OH
Dr. Wolf's CHM 201 & 202
15-4
Ethanol
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.
Dr. Wolf's CHM 201 & 202
15-5
Other alcohols
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.
Dr. Wolf's CHM 201 & 202
15-6
Sources of alcohols
Reactions discussed in earlier chapters (Table 15.1)
Hydration of alkenes
Hydroboration-oxidation of alkenes
Hydrolysis of alkyl halides
Syntheses using
Grignard reagents
organolithium reagents
Dr. Wolf's CHM 201 & 202
15-7
Sources of alcohols
New methods in Chapter 15
Reduction of aldehydes and ketones
Reduction of carboxylic acids
Reduction of esters
Reaction of Grignard reagents with epoxides
Diols by hydroxylation of alkenes
Dr. Wolf's CHM 201 & 202
15-8
Preparation of Alcohols
by
Reduction of Aldehydes and Ketones
Dr. Wolf's CHM 201 & 202
15-9
Reduction of Aldehydes Gives Primary Alcohols
R
R
C
H
Dr. Wolf's CHM 201 & 202
O
H
C
OH
H
15-10
Example: Catalytic Hydrogenation
O
CH3O
CH
+
H2
Pt, ethanol
CH3O
CH2OH
(92%)
Dr. Wolf's CHM 201 & 202
15-11
Reduction of Ketones Gives Secondary Alcohols
R
R
C
R'
Dr. Wolf's CHM 201 & 202
O
H
C
OH
R'
15-12
Example: Catalytic Hydrogenation
H
O
+
H2
OH
Pt
ethanol
(93-95%)
Dr. Wolf's CHM 201 & 202
15-13
Retrosynthetic Analysis
R
H
C
R
OH
H:–
R
C
R'
Dr. Wolf's CHM 201 & 202
O
C
O
H
H
H
C
R
OH
H:–
R'
15-14
Metal Hydride Reducing Agents
H
H
+
Na H
–
B
H
Li
+
Al
H
H
H
Sodium
borohydride
H
–
Lithium
aluminum hydride
act as hydride donors
Dr. Wolf's CHM 201 & 202
15-15
Examples: Sodium Borohydride
Aldehyde
O2N
O2N
O
NaBH4
CH2OH
CH
methanol
(82%)
Ketone
O
NaBH4
ethanol
Dr. Wolf's CHM 201 & 202
H OH
(84%)
15-16
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 & 202
15-17
Examples: Lithium Aluminum Hydride
Aldehyde
O
CH3(CH2)5CH
1. LiAlH4
diethyl ether
2. H2O
CH3(CH2)5CH2OH
(86%)
Ketone
O
(C6H5)2CHCCH3
Dr. Wolf's CHM 201 & 202
1. LiAlH4
diethyl ether
2. H2O
OH
(C6H5)2CHCHCH3
(84%)
15-18
Selectivity
neither NaBH4 or LiAlH4
reduces isolated
double bonds
O
1. LiAlH4
diethyl ether
2. H2O
(90%)
H
Dr. Wolf's CHM 201 & 202
OH
15-19
Preparation of Alcohols By Reduction
of Carboxylic Acids and Esters
Dr. Wolf's CHM 201 & 202
15-20
Reduction of Carboxylic Acids
Gives Primary Alcohols
R
R
C
HO
O
H
C
OH
H
lithium aluminum hydride is only
effective reducing agent
Dr. Wolf's CHM 201 & 202
15-21
Example: Reduction of a Carboxylic Acid
O
COH
1. LiAlH4
diethyl ether
2. H2O
CH2OH
(78%)
Dr. Wolf's CHM 201 & 202
15-22
Reduction of Esters
Gives Primary Alcohols
(Also Chapter 19)
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
Dr. Wolf's CHM 201 & 202
15-23
Example: Reduction of an Ester
O
COCH2CH3
1. LiAlH4
diethyl ether
2. H2O
CH2OH +
CH3CH2OH
(90%)
Dr. Wolf's CHM 201 & 202
15-24
Preparation of Alcohols From Epoxides
Dr. Wolf's CHM 201 & 202
15-25
Reaction of Grignard Reagents
with Epoxides
R
MgX
CH2
H2C
O
R
CH2
CH2
OMgX
H3O+
RCH2CH2OH
Dr. Wolf's CHM 201 & 202
15-26
Example
CH2
CH3(CH2)4CH2MgBr + H2C
O
1. diethyl ether
2. H3O+
CH3(CH2)4CH2CH2CH2OH
(71%)
Dr. Wolf's CHM 201 & 202
15-27
Preparation of Diols
Dr. Wolf's CHM 201 & 202
15-28
Diols are prepared by...
reactions used to prepare alcohols
hydroxylation of alkenes
Dr. Wolf's CHM 201 & 202
15-29
Example: reduction of a dialdehyde
O
O
HCCH2CHCH2CH
CH3
H2 (100 atm)
Ni, 125°C
HOCH2CH2CHCH2CH2OH
CH3
3-Methyl-1,5-pentanediol
(81-83%)
Dr. Wolf's CHM 201 & 202
15-30
Hydroxylation of Alkenes
Gives Vicinal Diols
vicinal diols have hydroxyl groups on adjacent
carbons
ethylene glycol (HOCH2CH2OH) is most familiar
example
Dr. Wolf's CHM 201 & 202
15-31
Osmium Tetraoxide is Key Reagent
syn addition of —OH groups to each carbon
of double bond
C
C
C
C
HO
C
OH
C
O
O
Os
O
Dr. Wolf's CHM 201 & 202
O
15-32
Example
CH3(CH2)7CH
CH2
(CH3)3COOH
OsO4 (cat)
tert-Butyl alcohol
HO–
CH3(CH2)7CHCH2OH
OH
(73%)
Dr. Wolf's CHM 201 & 202
15-33
Example
H
(CH3)3COOH
OsO4 (cat)
H
tert-Butyl alcohol
HO–
H
H
HO
OH
(62%)
Dr. Wolf's CHM 201 & 202
15-34
Reactions of Alcohols:
A Review and a Preview
Dr. Wolf's CHM 201 & 202
15-35
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 & 202
15-36
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 & 202
15-37
Conversion of Alcohols to Ethers
Dr. Wolf's CHM 201 & 202
15-38
Conversion of Alcohols to Ethers
RCH2O
CH2R
H
OH
H+
RCH2O
CH2R
+
H
OH
acid-catalyzed
referred to as a "condensation"
equilibrium; most favorable for primary alcohols
Dr. Wolf's CHM 201 & 202
15-39
Example
2CH3CH2CH2CH2OH
H2SO4, 130°C
CH3CH2CH2CH2OCH2CH2CH2CH3
(60%)
Dr. Wolf's CHM 201 & 202
15-40
Mechanism of Formation of Diethyl Ether
Step 1:
••
CH3CH2O ••
H
OSO2OH
H
+
CH3CH2O ••
H
+
–
OSO2OH
H
Dr. Wolf's CHM 201 & 202
15-41
Mechanism of Formation of Diethyl Ether
Step 2:
H
CH3CH2 +O ••
H
••
CH3CH2
+
CH3CH2O ••
H
+
• O ••
•
H
H
CH3CH2O ••
H
Dr. Wolf's CHM 201 & 202
15-42
Mechanism of Formation of Diethyl Ether
Step 3:
CH3CH2
CH3CH2
+
CH3CH2O ••
CH3CH2O ••
••
H
••
•• OSO OH
2
••
–
Dr. Wolf's CHM 201 & 202
+
H
••
OSO2OH
••
15-43
Intramolecular Analog
HOCH2CH2CH2CH2CH2OH
130°
H2SO4
O
reaction normally works well
only for 5- and 6-membered
rings
(76%)
Dr. Wolf's CHM 201 & 202
15-44
Intramolecular Analog
HOCH2CH2CH2CH2CH2OH
via:
130°
H2SO4
••
•• O
O
H
H
O •• +
H
(76%)
Dr. Wolf's CHM 201 & 202
15-45
Esterification
(more on esters and other
acid derivatives in later
chapters)
Dr. Wolf's CHM 201 & 202
15-46
Esterification
O
ROH +
O
H+
R'COH
R'COR +
H2O
a condensation reaction
called Fischer esterification
acid catalyzed
reversible
Dr. Wolf's CHM 201 & 202
15-47
Example of Fischer Esterification
O
COH + CH3OH
0.1 mol
0.6 mol (i.e. excess)
H2SO4
O
COCH3 +
H2O
70% yield based on benzoic acid
Dr. Wolf's CHM 201 & 202
15-48
Reaction of Alcohols with Acyl Chlorides
O
ROH +
R'CCl
O
R'COR +
HCl
high yields
not reversible when carried out
in presence of pyridine
Dr. Wolf's CHM 201 & 202
15-49
Example
CH3CH2
O
OH
+
O2N
CCl
CH3
pyridine
CH3CH2
O
NO2
OC
CH3
Dr. Wolf's CHM 201 & 202
(63%)
15-50
Reaction of Alcohols with Acid Anhydrides
O O
ROH + R'COCR'
O
R'COR +
O
R'COH
analogous to reaction with acyl chlorides
Dr. Wolf's CHM 201 & 202
15-51
Example
O O
C6H5CH2CH2OH + F3CCOCCF3
pyridine
O
C6H5CH2CH2OCCF3
(83%)
Dr. Wolf's CHM 201 & 202
15-52
Esters of Inorganic Acids
Dr. Wolf's CHM 201 & 202
15-53
Esters of Inorganic Acids
ROH + HOEWG
ROEWG + H2O
EWG is an electron-withdrawing group
+
HONO2
(HO)2SO2
(HO)3P
Dr. Wolf's CHM 201 & 202
–
O
15-54
Esters of Inorganic Acids
ROH + HOEWG
ROEWG + H2O
EWG is an electron-withdrawing group
+
HONO2
(HO)2SO2
(HO)3P
CH3OH + HONO2
–
O
CH3ONO2 + H2O
(66-80%)
Dr. Wolf's CHM 201 & 202
15-55
Oxidation of Alcohols
Dr. Wolf's CHM 201 & 202
15-56
Oxidation of Alcohols
Primary alcohols
O
O
RCH2OH
RCH
RCOH
Secondary alcohols
OH
O
RCHR'
RCR'
Dr. Wolf's CHM 201 & 202
from H2O
15-57
Typical Oxidizing Agents
Aqueous solution
Mn(VII)
Cr(VI)
KMnO4
H2CrO4
H2Cr2O7
Dr. Wolf's CHM 201 & 202
15-58
Aqueous Cr(VI)
FCH2CH2CH2CH2OH
K2Cr2O7
H2SO4
H2O
O
FCH2CH2CH2COH
(74%)
Dr. Wolf's CHM 201 & 202
15-59
Aqueous Cr(VI)
H
FCH2CH2CH2CH2OH
OH
K2Cr2O7
H2SO4
H2O
Na2Cr2O7
H2SO4
H2O
O
O
FCH2CH2CH2COH
(74%)
Dr. Wolf's CHM 201 & 202
(85%)
15-60
Nonaqueous Sources of Cr(VI)
All are used in CH2Cl2
Pyridinium dichromate (PDC)
(C5H5NH+)2 Cr2O72–
Pyridinium chlorochromate (PCC)
C5H5NH+ ClCrO3–
Dr. Wolf's CHM 201 & 202
15-61
Example: Oxidation of
a primary alcohol with PCC
(pyridinium chlorochromate)
ClCrO3–
+N
H
PCC
CH3(CH2)5CH2OH
O
CH3(CH2)5CH
CH2Cl2
(78%)
Dr. Wolf's CHM 201 & 202
15-62
Example: Oxidation of
a primary alcohol with PDC
(pryidinium dichromate)
(CH3)3C
CH2OH
PDC
CH2Cl2
O
(CH3)3C
CH
(94%)
Dr. Wolf's CHM 201 & 202
15-63
Mechanism
H
C
O
HOCrOH
OH
O
H
O
C
O
CrOH
O
involves formation
and elimination of
a chromate ester
Dr. Wolf's CHM 201 & 202
15-64
H
Mechanism
••
O
H
••
H
C
O
HOCrOH
OH
O
H
O
C
O
CrOH
O
involves formation
and elimination of
a chromate ester
C
Dr. Wolf's CHM 201 & 202
O
15-65
Biological Oxidation of Alcohols
Dr. Wolf's CHM 201 & 202
15-66
Enzyme-catalyzed
CH3CH2OH
+
NAD
+
(a coenzyme)
alcohol
dehydrogenase
CH3CH
Dr. Wolf's CHM 201 & 202
O
+ NAD
H
+
H+
15-67
Figure 15.3 Structure of NAD+
O
O
HO
O
_
OO
P
O
_
O
P
H
O
OH
N
HO
O
N
HO
N
+
NH2
C
O
NH2
nicotinamide adenine dinucleotide (oxidized form)
Dr. Wolf's CHM 201 & 202
15-68
Enzyme-catalyzed
H
O
CNH2
CH3CH2OH +
+
N
+
H+
R
Dr. Wolf's CHM 201 & 202
15-69
Enzyme-catalyzed
H
H
O
CH3CH
O
CNH2
••
N
R
Dr. Wolf's CHM 201 & 202
15-70
Oxidative Cleavage of Vicinal Diols
Dr. Wolf's CHM 201 & 202
15-71
Cleavage of Vicinal Diols by Periodic Acid
C
HIO4
C
HO
Dr. Wolf's CHM 201 & 202
C
O + O
C
OH
15-72
Cleavage of Vicinal Diols by Periodic Acid
CH3
CH
HO
CCH3
OH
HIO4
O
CH
O
+
CH3CCH3
(83%)
Dr. Wolf's CHM 201 & 202
15-73
Cyclic Diols are Cleaved
OH
HIO4
O
O
HCCH2CH2CH2CH
OH
Dr. Wolf's CHM 201 & 202
15-74
Preparation of Thiols
Dr. Wolf's CHM 201 & 202
15-75
Nomenclature of Thiols
1) analogous to alcohols, but suffix is -thiol
rather than -ol
2) final -e of alkane name is retained, not
dropped as with alcohols
Dr. Wolf's CHM 201 & 202
15-76
Nomenclature of Thiols
1) analogous to alcohols, but suffix is -thiol
rather than -ol
2) final -e of alkane name is retained, not
dropped as with alcohols
CH3CHCH2CH2SH
CH3
3-Methyl-1-butanethiol
Dr. Wolf's CHM 201 & 202
15-77
Properties of Thiols
1. low molecular weight thiols have foul odors
2. hydrogen bonding is much weaker in thiols than
in alcohols
3. thiols are stronger acids than alcohols
4. thiols are more easily oxidized than alcohols;
oxidation takes place at sulfur
Dr. Wolf's CHM 201 & 202
15-82
Thiols are less polar than alcohols
Methanol
Methanethiol
bp: 65°C
bp: 6°C
Thiols are stronger acids than alcohols
have pKas of about 10; can be deprotonated in
aqueous base
••
RS
••
– ••
H + •• OH
stronger acid
(pKa = 10)
Dr. Wolf's CHM 201 & 202
••
•• –
RS ••
••
+
H
••
OH
••
weaker acid
(pKa = 15.7)
15-83
RS– and HS – are weakly basic and good nucleophiles
C6H5S H
H Cl
C6H5SNa
(75%)
SN2
KSH
Br
SN2
SH
(67%)
Oxidation of thiols take place at sulfur
••
RS
••
H
thiol (reduced)
••
RS
••
••
SR
••
disulfide (oxidized)
thiol-disulfide redox pair is important in
biochemistry
other oxidative processes place 1, 2, or 3
oxygen atoms on sulfur
Dr. Wolf's CHM 201 & 202
15-84
Oxidation of thiols take place at sulfur
••
RS
••
H
thiol
••
RS
••
••
SR
••
disulfide
•• –
•• O ••
••
RS
••
OH
sulfenic acid
Dr. Wolf's CHM 201 & 202
+
RS OH
••
sulfinic acid
•• –
•• O ••
2+
RS
OH
•• O ••
••
–
sulfonic acid
15-85
Example: sulfide-disulfide redox pair
SH
O
HSCH2CH2CH(CH2)4COH
O2, FeCl3
S
S
O
(CH2)4COH
Dr. Wolf's CHM 201 & 202
a-Lipoic acid (78%)
15-86
Spectroscopic Analysis of Alcohols
Dr. Wolf's CHM 201 & 202
15-87
Infrared Spectroscopy
O—H stretching: 3200-3650 cm–1 (broad)
C—O stretching: 1025-1200 cm–1 (broad)
Dr. Wolf's CHM 201 & 202
15-88
Figure 15.4: Infrared Spectrum of Cyclohexanol
OH
C—H
O—H
C—O
3500
3000
2500
2000
1500
1000
500
Wave number, cm-1
Dr. Wolf's CHM 201 & 202
15-89
1H
NMR
chemical shift of O—H proton is variable;
depends on temperature and concentration
O—H proton can be identified by adding D2O;
signal for O—H disappears (converted to O—D)
H
d 3.3-4 ppm
Dr. Wolf's CHM 201 & 202
C
O
H
d 0.5-5 ppm
15-90
Figure 15.5 (page 607)
CH2CH2OH
10.0
9.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
0
Chemical shift (d, ppm)
Dr. Wolf's CHM 201 & 202
15-91
13C
NMR
chemical shift of C—OH is d 60-75 ppm
C—O is about 35-50 ppm less shielded than C—H
CH3CH2CH2CH3
d 13 ppm
Dr. Wolf's CHM 201 & 202
CH3CH2CH2CH2OH
d 61.4 ppm
15-92
UV-VIS
Unless there are other chromophores in the
molecule, alcohols are transparent above
about 200 nm;
lmax for methanol, for example, is 177 nm.
Dr. Wolf's CHM 201 & 202
15-93
Mass Spectrometry of Alcohols
molecular ion peak is usually small
a peak corresponding to loss of H2O
from the molecular ion (M - 18) is
usually present
peak corresponding to loss of an
alkyl group to give an oxygenstabilized carbocation is usually
prominent
Dr. Wolf's CHM 201 & 202
15-94
Mass Spectrometry of Alcohols
molecular ion peak is usually small
R
a peak corresponding to loss of H2O
from the molecular ion (M - 18) is
usually present
peak corresponding to loss of an
alkyl group to give an oxygenstabilized carbocation is usually
prominent
R
R•
Dr. Wolf's CHM 201 & 202
CH2
••
OH
••
•+
CH2
OH
CH2
+
OH
••
••
15-95
End of Chapter 15