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Chapter 15
Alcohols, Diols, and Thiols
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Sources of Alcohols
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
Sources of Alcohols
New methods in Chapter 15
Reduction of aldehydes and ketones
Reduction of carboxylic acids
Reaction of Grignard reagents with epoxides
Diols by hydroxylation of alkenes
Preparation of Alcohols
by
Reduction of Aldehydes and Ketones
Reduction of Aldehydes Gives Primary Alcohols
R
R
C
H
O
H
C
H
OH
Example: Catalytic Hydrogenation
O
CH3O
CH
+
H2
Pt, ethanol
CH3O
CH2OH
(92%)
Reduction of Ketones Gives Secondary Alcohols
R
R
C
R'
O
H
C
R'
OH
Example: Catalytic Hydrogenation
H
O
+
H2
OH
Pt
ethanol
(93-95%)
Retrosynthetic Analysis
R
H
C
R
OH
H:–
R
C
R'
O
C
O
H
H
H
C
R
OH
H:–
R'
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
Examples: Sodium Borohydride
Aldehyde
O2N
O2N
O
NaBH4
CH2OH
CH
methanol
(82%)
Ketone
O
NaBH4
ethanol
H OH
(84%)
Lithium Aluminum Hydride
More reactive than sodium borohydride.
Cannot use water, ethanol, methanol etc.
as solvents.
Diethyl ether is most commonly used solvent.
Examples: Lithium Aluminum Hydride
Aldehyde
O
CH3(CH2)5CH
1. LiAlH4
diethyl ether
2. H2O
CH3(CH2)5CH2OH
(86%)
Ketone
O
(C6H5)2CHCCH3
1. LiAlH4
diethyl ether
2. H2O
OH
(C6H5)2CHCHCH3
(84%)
Selectivity
Neither NaBH4 or LiAlH4
reduces carbon-carbon
double bonds.
O
1. LiAlH4
diethyl ether
2. H2O
(90%)
H
OH
Preparation of Alcohols By Reduction
of Carboxylic Acids
Reduction of Carboxylic Acids
Gives Primary Alcohols
R
R
C
HO
O
H
C
H
lithium aluminum hydride is only
effective reducing agent
OH
Example: Reduction of a Carboxylic Acid
O
COH
1. LiAlH4
diethyl ether
2. H2O
CH2OH
(78%)
Preparation of Alcohols From Epoxides
Reaction of Grignard Reagents
with Epoxides
R
MgX
CH2
H2C
O
R
CH2
CH2
OMgX
H3O+
RCH2CH2OH
Example
CH2
CH3(CH2)4CH2MgBr + H2C
O
1. diethyl ether
2. H3O+
CH3(CH2)4CH2CH2CH2OH
(71%)
Preparation of Diols
Diols are Prepared by...
Reactions used to prepare alcohols
Hydroxylation of alkenes
Example: Reduction of a Dialdehyde
O
O
HCCH2CHCH2CH
CH3
H2 (100 atm)
Ni, 125°C
HOCH2CH2CHCH2CH2OH
CH3
3-Methyl-1,5-pentanediol
(81-83%)
Hydroxylation of Alkenes
Gives Vicinal Diols
Vicinal diols have hydroxyl groups on adjacent
carbons.
Ethylene glycol (HOCH2CH2OH) is most familiar
example.
Osmium Tetraoxide is Key Reagent
C
C
C
C
HO
C
OsO4
C
O
O
Os
O
O
Cyclic osmate ester
OH
Example
CH3(CH2)7CH
CH2
(CH3)3COOH
OsO4 (cat)
tert-Butyl alcohol
HO–
CH3(CH2)7CHCH2OH
OH
(73%)
Example
Stereospecific
syn addition of —OH groups to each carbon
of double bond
H
(CH3)3COOH
OsO4 (cat)
H
tert-Butyl alcohol
HO–
H
H
HO
OH
(62%)
Reactions of Alcohols:
A Review and a Preview
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Table 15.2 Review of Reactions of Alcohols
Reaction with hydrogen halides
Reaction with thionyl chloride
Reaction with phosphorous trihalides
Acid-catalyzed dehydration
Conversion to p-toluenesulfonate esters
New Reactions of Alcohols in This Chapter
Conversion to ethers
Esterification
Oxidation
Cleavage of vicinal diols
Conversion of Alcohols to Ethers
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
Example
2CH3CH2CH2CH2OH
H2SO4, 130°C
CH3CH2CH2CH2OCH2CH2CH2CH3
(60%)
Mechanism of Formation of Diethyl Ether
Step 1:
••
CH3CH2O ••
H
OSO2OH
H
+
CH3CH2O ••
H
+
H
–
OSO2OH
Mechanism of Formation of Diethyl Ether
Step 2:
H
CH3CH2 +O ••
H
••
CH3CH2
+
CH3CH2O ••
H
+
• O ••
•
H
H
CH3CH2O ••
H
Mechanism of Formation of Diethyl Ether
Step 3:
CH3CH2
CH3CH2
+
CH3CH2O ••
CH3CH2O ••
+
••
H
H
••
•• OCH CH
2
3
H
•• OCH CH
2
3
H
+
Intramolecular Analogue
HOCH2CH2CH2CH2CH2OH
via:
H2SO4
130°
••
•• O
O
(76%)
H
Reaction normally works well only for
5- and 6-membered rings.
H
O •• +
H
Esterification
Esterification
O
ROH +
O
H+
R'COR +
R'COH
condensation
Fischer esterification
acid catalyzed
reversible
H2O
Example of Fischer Esterification
O
COH + CH3OH
0.1 mol
0.6 mol
H2SO4
O
COCH3 +
H2O
70% yield based on benzoic acid
Reaction of Alcohols with Acyl Chlorides
O
ROH +
R'CCl
O
R'COR +
High yields
Not reversible when carried out
in presence of pyridine.
HCl
Example
CH3CH2
O
OH
+
O2N
CCl
CH3
pyridine
CH3CH2
O
NO2
OC
CH3
(63%)
Reaction of Alcohols with Acid Anhydrides
O O
ROH + R'COCR'
O
R'COR +
O
R'COH
analogous to reaction with acyl chlorides
Example
O O
C6H5CH2CH2OH + F3CCOCCF3
pyridine
O
C6H5CH2CH2OCCF3
(83%)
Oxidation of Alcohols
Oxidation of Alcohols
Primary alcohols
O
O
RCH2OH
RCH
RCOH
Secondary alcohols
OH
O
RCHR'
RCR'
from H2O
Typical Oxidizing Agents
Aqueous solution
Mn(VII)
Cr(VI)
KMnO4
H2CrO4
H2Cr2O7
Aqueous Cr(VI)
H
FCH2CH2CH2CH2OH
OH
K2Cr2O7
H2SO4
H2O
Na2Cr2O7
H2SO4
H2O
O
O
FCH2CH2CH2COH
(74%)
(85%)
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
O
Nonaqueous Sources of Cr(VI)
All are used in CH2Cl2
Pyridinium dichromate (PDC)
(C5H5NH+)2 Cr2O72–
Pyridinium chlorochromate (PCC)
C5H5NH+ ClCrO3–
Example: Oxidation of
a Primary Alcohol with PCC
ClCrO3–
+N
H
PCC
CH3(CH2)5CH2OH
O
CH3(CH2)5CH
CH2Cl2
(78%)
Example: Oxidation of
a Primary Alcohol with PDC
(CH3)3C
CH2OH
PDC
CH2Cl2
O
(CH3)3C
CH
(94%)
Oxidative Cleavage of Vicinal Diols
Cleavage of Vicinal Diols by Periodic Acid
C
HO
HIO4
C
OH
C
O + O
C
Cleavage of Vicinal Diols by Periodic Acid
CH3
CH
HO
CCH3
OH
HIO4
O
CH
(83%)
O
+
CH3CCH3
Cyclic Diols are Cleaved
OH
HIO4
O
O
HCCH2CH2CH2CH
OH