Chapter 15 Alcohols, Diols, and Thiols

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Chapter 15Alcohols, Diols, and Thiols
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Sources of Alcohols
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Methanol

• Methanol is an industrial chemical
• end uses solvent, antifreeze, fuel
• principal use preparation of formaldehyde

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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
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Ethanol

• Ethanol is an industrial chemical
• Most ethanol comes from fermentation
• Synthetic ethanol is produced by hydrationof
  ethylene
• Synthetic ethanol is denatured (madeunfit for
  drinking) by adding methanol, benzene,pyridine,
  castor oil, gasoline, etc.

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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.

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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

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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

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Preparation of AlcoholsbyReduction of Aldehydes
and Ketones
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Reduction of Aldehydes Gives Primary Alcohols
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Example Catalytic Hydrogenation
Pt, ethanol

(92)
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Reduction of Ketones Gives Secondary Alcohols
R
C
O
R'
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Example Catalytic Hydrogenation
H
OH
Pt

H2
ethanol
(93-95)

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Retrosynthetic Analysis
H
H
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Metal Hydride Reducing Agents
Sodiumborohydride
Lithiumaluminum hydride

• act as hydride donors

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Examples Sodium Borohydride
Aldehyde
NaBH4
CH2OH
methanol
(82)
Ketone

NaBH4
ethanol
(84)
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Lithium aluminum hydride

• more reactive than sodium borohydride
• cannot use water, ethanol, methanol etc.as
  solvents
• diethyl ether is most commonly used solvent

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Examples Lithium Aluminum Hydride
Aldehyde
1. LiAlH4diethyl ether
CH3(CH2)5CH2OH
2. H2O
(86)
Ketone

1. LiAlH4diethyl ether
(C6H5)2CHCCH3
2. H2O
(84)
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Selectivity

• neither NaBH4 or LiAlH4reduces isolateddouble
  bonds

1. LiAlH4diethyl ether
2. H2O
(90)
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Preparation of Alcohols By Reductionof
Carboxylic Acids and Esters
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Reduction of Carboxylic AcidsGives Primary
Alcohols
R
C
O
HO

• lithium aluminum hydride is only effective
  reducing agent

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Example Reduction of a Carboxylic Acid
1. LiAlH4diethyl ether
2. H2O
(78)
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Reduction of EstersGives Primary Alcohols(Also
Chapter 19)

• Lithium aluminum hydride preferred forlaboratory
  reductions
• Sodium borohydride reduction is too slowto be
  useful
• Catalytic hydrogenolysis used in industrybut
  conditions difficult or dangerous to duplicate
  in the laboratory (special catalyst,
  hightemperature, high pressure

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Example Reduction of an Ester
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Preparation of Alcohols From Epoxides
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Reaction of Grignard Reagentswith Epoxides
R
CH2
CH2
OMgX

H3O
RCH2CH2OH
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Example
CH2
H2C
CH3(CH2)4CH2MgBr


O
1. diethyl ether 2. H3O
CH3(CH2)4CH2CH2CH2OH
(71)
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Preparation of Diols
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Diols are prepared by...

• reactions used to prepare alcohols
• hydroxylation of alkenes

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Example reduction of a dialdehyde
H2 (100 atm)
Ni, 125C
3-Methyl-1,5-pentanediol
(81-83)
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Hydroxylation of AlkenesGives Vicinal Diols

• vicinal diols have hydroxyl groups on adjacent
  carbons
• ethylene glycol (HOCH2CH2OH) is most familiar
  example

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Osmium Tetraoxide is Key Reagent

• syn addition of OH groups to each carbonof
  double bond

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Example
(73)
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Example
(CH3)3COOHOsO4 (cat)
tert-Butyl alcoholHO
(62)
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Reactions of AlcoholsA Review and a Preview
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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

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New Reactions of Alcohols in This Chapter

• conversion to ethers
• esterification
• esters of inorganic acids
• oxidation
• cleavage of vicinal diols

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Conversion of Alcohols to Ethers
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Conversion of Alcohols to Ethers
H

• acid-catalyzed
• referred to as a "condensation"
• equilibrium most favorable for primary alcohols

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Example
2CH3CH2CH2CH2OH
CH3CH2CH2CH2OCH2CH2CH2CH3
(60)
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Mechanism of Formation of Diethyl Ether
Step 1
H
H



OSO2OH
CH3CH2O

H
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Mechanism of Formation of Diethyl Ether
Step 2

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Mechanism of Formation of Diethyl Ether
Step 3

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Intramolecular Analog
HOCH2CH2CH2CH2CH2OH
130
H2SO4

• reaction normally works wellonly for 5- and
  6-memberedrings

(76)
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Intramolecular Analog
HOCH2CH2CH2CH2CH2OH
via
130
H2SO4
(76)
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Esterification(more on esters and other acid
derivatives in later chapters)
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Esterification
H


ROH
H2O

• a condensation reaction
• called Fischer esterification
• acid catalyzed
• reversible

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Example of Fischer Esterification
0.1 mol
0.6 mol (i.e. excess)

H2O

• 70 yield based on benzoic acid

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Reaction of Alcohols with Acyl Chlorides


ROH
HCl

• high yields
• not reversible when carried outin presence of
  pyridine

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Example

pyridine
(63)
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Reaction of Alcohols with Acid Anhydrides


ROH

• analogous to reaction with acyl chlorides

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Example
pyridine
(83)
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Esters of Inorganic Acids
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Esters of Inorganic Acids
ROH HOEWG
ROEWG H2O
EWG is an electron-withdrawing group

HONO2
(HO)2SO2
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Esters of Inorganic Acids
ROH HOEWG
ROEWG H2O
EWG is an electron-withdrawing group

HONO2
(HO)2SO2
CH3OH HONO2
CH3ONO2 H2O
(66-80)
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Oxidation of Alcohols
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Oxidation of Alcohols
Primary alcohols
RCH2OH
RCH
RCOH
Secondary alcohols
from H2O
RCR'
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Typical Oxidizing Agents

• Aqueous solution
• Mn(VII) Cr(VI)
• KMnO4 H2CrO4
• H2Cr2O7

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Aqueous Cr(VI)
FCH2CH2CH2CH2OH
H2SO4
K2Cr2O7
H2O
FCH2CH2CH2COH
(74)
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Aqueous Cr(VI)
FCH2CH2CH2CH2OH
H2SO4
K2Cr2O7
H2SO4
H2O
Na2Cr2O7
H2O
FCH2CH2CH2COH
(74)
(85)
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Nonaqueous Sources of Cr(VI)

• All are used in CH2Cl2
• Pyridinium dichromate (PDC)
• (C5H5NH)2 Cr2O72
• Pyridinium chlorochromate (PCC)
• C5H5NH ClCrO3

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Example Oxidation of a primary alcohol with
PCC(pyridinium chlorochromate)
ClCrO3
PCC
CH3(CH2)5CH2OH
CH2Cl2
(78)
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Example Oxidation of a primary alcohol with
PDC(pryidinium dichromate)
PDC
CH2Cl2
(94)
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Mechanism
H
H
C
C
HOCrOH
CrOH
OH
O

• involves formation and elimination of a chromate
  ester

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Mechanism
H
H
H
H
C
C
HOCrOH
CrOH
OH
O

• involves formation and elimination of a chromate
  ester

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Biological Oxidation of Alcohols
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Enzyme-catalyzed

CH3CH2OH
alcohol dehydrogenase


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Figure 15.3 Structure of NAD

• nicotinamide adenine dinucleotide (oxidized form)

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Enzyme-catalyzed

CH3CH2OH

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Enzyme-catalyzed
H
H

N
R
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Oxidative Cleavage of Vicinal Diols
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Cleavage of Vicinal Diols by Periodic Acid

C
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Cleavage of Vicinal Diols by Periodic Acid
HIO4

(83)
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Cyclic Diols are Cleaved
HIO4
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Preparation of Thiols
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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

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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

3-Methyl-1-butanethiol
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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

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Thiols are less polar than alcohols
Methanol
Methanethiol
bp 65C
bp 6C
80
Thiols are stronger acids than alcohols

• have pKas of about 10 can be deprotonated in
  aqueous base

RS

stronger acid(pKa 10)
weaker acid(pKa 15.7)
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RS and HS are weakly basic and good
nucleophiles
82
Oxidation of thiols take place at sulfur
thiol (reduced)
disulfide (oxidized)

• thiol-disulfide redox pair is important in
  biochemistry
• other oxidative processes place 1, 2, or 3
  oxygen atoms on sulfur

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Oxidation of thiols take place at sulfur
thiol
disulfide


O


2
RS
OH
O




sulfinic acid
sulfenic acid
sulfonic acid
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Example sulfide-disulfide redox pair
SH
HSCH2CH2CH(CH2)4COH
O2, FeCl3
S
S
a-Lipoic acid (78)
(CH2)4COH
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Spectroscopic Analysis of Alcohols
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Infrared Spectroscopy

• OH stretching 3200-3650 cm1 (broad)
• CO stretching 1025-1200 cm1 (broad)

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Figure 15.4 Infrared Spectrum of Cyclohexanol
CH
OH
CO
Wave number, cm-1
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1H NMR

• chemical shift of OH proton is variable
  depends on temperature and concentration
• OH proton can be identified by adding D2O
  signal for OH disappears (converted to OD)

H
H
C
O
d 3.3-4 ppm
d 0.5-5 ppm
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Figure 15.5 (page 607)
Chemical shift (d, ppm)
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13C NMR

• chemical shift of COH is d 60-75 ppm
• CO is about 35-50 ppm less shielded than CH

CH3CH2CH2CH3
CH3CH2CH2CH2OH
d 13 ppm
d 61.4 ppm
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UV-VIS
Unless there are other chromophores in
themolecule, alcohols are transparent
aboveabout 200 nm lmax for methanol, for
example, is 177 nm.
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Mass Spectrometry of Alcohols

• molecular ion peak is usually small
• a peak corresponding to loss of H2Ofrom the
  molecular ion (M - 18) isusually present
• peak corresponding to loss of analkyl group to
  give an oxygen-stabilized carbocation is
  usuallyprominent

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Mass Spectrometry of Alcohols

• molecular ion peak is usually small
• a peak corresponding to loss of H2Ofrom the
  molecular ion (M - 18) isusually present
• peak corresponding to loss of analkyl group to
  give an oxygen-stabilized carbocation is
  usuallyprominent

CH2
OH

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End of Chapter 15