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15.6
Reactions of Alcohols:
A Review and a Preview
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
New Reactions of Alcohols in This Chapter
conversion to ethers
esterification
esters of inorganic acids
oxidation
cleavage of vicinal diols
15.7
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%)
Figure 15.2 Mechanism of Formation of Diethyl Ether
Step 1:
••
CH3CH2O ••
H
OSO2OH
H
+
CH3CH2O ••
H
+
H
–
OSO2OH
Figure 15.2 Mechanism of Formation of Diethyl Ether
Step 2:
H
CH3CH2 +O ••
H
••
CH3CH2
+
CH3CH2O ••
H
+
• O ••
•
H
H
CH3CH2O ••
H
Figure 15.2 Mechanism of Formation of Diethyl Ether
Step 3:
CH3CH2
CH3CH2
+
CH3CH2O ••
CH3CH2O ••
+
••
H
••
•• OSO OH
2
••
–
H
••
OSO2OH
••
Intramolecular Analog
HOCH2CH2CH2CH2CH2OH
130°
H2SO4
O
(76%)
reaction normally works well
only for 5- and 6-membered
rings
Intramolecular Analog
HOCH2CH2CH2CH2CH2OH
via:
130°
H2SO4
••
•• O
O
(76%)
H
H
O •• +
H
15.8
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%)
15.9
Esters of Inorganic Acids
Esters of Inorganic Acids
ROH + HOEWG
ROEWG + H2O
EWG is an electron-withdrawing group
+
HONO2
(HO)2SO2
(HO)3P
–
O
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%)
15.10
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)
FCH2CH2CH2CH2OH
K2Cr2O7
H2SO4
H2O
O
FCH2CH2CH2COH
(74%)
Aqueous Cr(VI)
H
FCH2CH2CH2CH2OH
OH
K2Cr2O7
H2SO4
H2O
Na2Cr2O7
H2SO4
H2O
O
O
FCH2CH2CH2COH
(74%)
(85%)
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%)
Mechanism
H
C
O
HOCrOH
OH
O
H
O
C
O
CrOH
O
involves formation
and elimination of
a chromate ester
••
Mechanism
O
••
H
C
O
HOCrOH
OH
O
H
O
C
O
CrOH
O
involves formation
and elimination of
a chromate ester
C
O
15.11
Biological Oxidation of Alcohols
Enzyme-catalyzed
CH3CH2OH
+
NAD
+
alcohol
dehydrogenase
CH3CH
O
+ NAD
H
+
H+
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)
Enzyme-catalyzed
H
O
CNH2
CH3CH2OH +
+
N
R
+
H+
Enzyme-catalyzed
H
H
O
CH3CH
O
CNH2
••
N
R
15.12
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