Chapter 15 Alcohols, Diols, and Thiols

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Chapter 15Alcohols, Diols, and Thiols
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15.1Sources of Alcohols
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Methanol

• Methanol is an industrial chemical
• 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 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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Natural Product Alcohols
Natural product - Any organic substance isolated
from living organisms or material derived from
living organisms.
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Review - Preparation of Alcohols
Hydroboration-oxidation of alkenes
Hydration of alkenes
Nucleophilic 1,2-addition of organometallic reagen
ts to carbonyl compounds
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New Ways to Prepare Alcohols

• Reduction of aldehydes and ketones.
• Reduction of carboxylic acids.
• Reduction of esters.
• Reaction of Grignard reagents with epoxides.
• 1,2-Diols by dihydroxylation of alkenes.

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15.2Preparation 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
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Metal Hydride Reducing Agents
Sodiumborohydride

• Both act as hydride (H) donors.

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Sodium Borohydride
Aldehyde
NaBH4
methanol
Ketone
NaBH4
ethanol
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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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Lithium Aluminum Hydride
Aldehyde

• LiAlH4,
• diethyl ether

2. H2O
Ketone

• LiAlH4,
• diethyl ether

(C6H5)2CHCCH3
2. H2O
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Selectivity

• Neither NaBH4 or LiAlH4reduces
  carbon-carbondouble bonds.

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15.3Preparation 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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Reduction of a Carboxylic Acid

• LiAlH4,
• diethyl ether

2. H2O
(78)
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Reduction of EstersGives Primary Alcohols

• Lithium aluminum hydride preferred forlaboratory
  reductions.
• Catalytic hydrogenation used in industrybut
  conditions difficult or dangerous to duplicate
  in the laboratory (special catalyst,
  hightemperature, high pressure).

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Reduction of an Ester
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15.4Preparation of Alcohols From Epoxides
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Reaction of Grignard Reagentswith Epoxides
CH2
H2C
CH3(CH2)4CH2MgBr

O
1. diethyl ether 2. H3O
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Reaction of Grignard Reagentswith Epoxides
Epoxide rings are strained (29 kcal mol-1) and
prone to nucleophilic attack at the carbon
centers.
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15.5Preparation of Diols
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Example Reduction of a Dialdehyde
H2 (100 atm)
Ni, 125C
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Hydroxylation of AlkenesGives Vicinal Diols

• Vicinal diols have hydroxyl groups on adjacent
  carbons.
• Ethylene glycol (HOCH2CH2OH), an antifreeze, is a
  familiar example.

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Osmium Tetraoxide is Key Reagent
OsO4
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Example
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Dihydroxylation with OsO4 Is a Sterespecific
Reaction
Only the cis-1,2-diol obtained because
of the mechanism of initial cycloaddition step
both oxygen atoms on OsO4 attack same face of the
alkene.
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15.6Reactions of AlcoholsA Review and a Preview
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Review of Reactions of Alcohols

• Reaction with hydrogen halides (alkyl halides).
• Reaction with thionyl chloride (alkyl chlorides).
• Reaction with phosphorous tribromide (alkyl
  bromides).
• Acid-catalyzed dehydration (alkenes).
• Conversion to p-toluenesulfonate esters
  (tosylates).

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New Reactions of Alcohols

• Conversion to ethers
• Esterification
• Esters of inorganic acids
• Oxidation
• Cleavage of vicinal diols

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15.7Conversion of Alcohols to Ethers
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Conversion of Alcohols to Ethers

Acid-catalyzed condensation of alcohols is an
equilibrium reaction most favorable for primary
alcohols and works best if water is removed.
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Example
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Mechanism of Formation of Diethyl Ether
Step 1
H
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Mechanism of Formation of Diethyl Ether
Unlike hydroxide (HO-), H2O is an excellent
leaving group, so acid catalysis is the key.
Step 2
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Mechanism of Formation of Diethyl Ether
Step 3
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Intramolecular Etherification
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15.8Esterification
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Esterification A Reversible Process
1) Fischer esterification (a classical
transformation). 2) Condensation process (H2O
produced). 3) Acid-catalyzed (H2SO4 is source of
H and dehydrating agent). 4) Reversible -
aqueous acid hydrolyzes esters to carboxylic
acids.
Acidic Dehydration
Acid Alcohol
Ester Water
Acidic Hydrolysis
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Example of Fischer Esterification
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Reaction of Alcohols with Acyl Chlorides
Advantages over Fischer Esterification? Fast,
high yields, mild conditions and not reversible.
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Example
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Reaction of Alcohols with Acid Anhydrides
Note similar behavior of acid anhydrides to acyl
chlorides.
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Example
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15.10Oxidation of Alcohols
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Oxidation of Alcohols
Primary alcohols
RCH2OH
RCH
RCOH
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Typical Oxidizing Agents

• Aqueous solution
• Mn(VII) Cr(VI)
• KMnO4 H2CrO4
• Na2Cr2O7
• K2Cr2O7

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Aqueous Cr(VI)
FCH2CH2CH2CH2OH
H2SO4,
K2Cr2O7
H2O
FCH2CH2CH2COH
(74)
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Mechanism
H
C
HOCrOH
OH

• Involves formation and elimination of a chromate
  ester.

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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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Oxidation of a Primary Alcohol with PDC
PDC
CH2Cl2
(94)
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Oxidation of a Primary Alcohol with PCC
ClCrO3
PCC
CH3(CH2)5CH2OH
CH2Cl2
(78)
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15.11Biological Oxidation of Alcohols
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Enzyme-Catalyzed
CH3CH2OH
alcohol dehydrogenase
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Structure of NAD

• Nicotinamide adenine dinucleotide (oxidized form)

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Enzyme-Catalyzed

CH3CH2OH
H
H



N
R
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15.12Oxidative Cleavage of Vicinal Diols
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Cleavage of Vicinal Diols by Periodic Acid
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Cleavage of Vicinal Diols by Periodic Acid
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Cyclic Diols Are Cleaved
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15.13Thiols
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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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Properties of Thiols

• 1) Hydrogen bonding is much weaker in thiols
  than in alcohols (SH bond is less polar than
  OH).
• 2) Low molecular weight thiols have foul odors.
• 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
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Thiols Are Stronger Acids than Alcohols

• Have pKas of about 10-11 can be deprotonated in
  aqueous base.

..
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RS and HS Are Weakly Basic and Good Nucleophiles
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Oxidation of Thiols Takes Place at Sulfur
Thiol
Disulfide

• 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 Takes Place at Sulfur
Thiol
Disulfide
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Sulfide-Disulfide Redox Pair
SH
6,8-Dimercaptooctanoic acid
HSCH2CH2CH(CH2)4COH
O2, FeCl3
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15.14Spectroscopic Analysis of Alcohols
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Infrared Spectroscopy

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

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Infrared Spectrum of Cyclohexanol
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Infrared Spectroscopy

• SH stretching 2550-2700 cm1 (weak)

Example 2-Mercaptoethanol HOCH2CH2SH
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1H NMR

• Chemical shift of OH proton is variable
  dependson temperature and concentration.
• OH proton can be identified by adding D2O
  signal for OH disappears (converted to OD).
• HCO signal is less shielded than HCH.

H
H
C
O
? 3.3-4 ppm
? 0.5-5 ppm
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2-Phenylethanol
Chemical shift (?, ppm)
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1H NMR

• Sulfur is less electronegative than oxygen, so it
  isless deshielding.

CH3CH2CH2CH2OH
CH3CH2CH2CH2SH
? 2.5
? 3.6
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13C NMR

• Chemical shift of COH is ? 60-75 ppm.
• Deshielding effect of O is much larger than that
  of S.