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Chapter 22
Phenols
Dr. Wolf's CHM 201 & 202
22 - 1
Nomenclature
Dr. Wolf's CHM 201 & 202
22 - 2
Nomenclature
OH
CH3
5-Chloro-2-methylphenol
Cl
named on basis of phenol as parent
substituents listed in alphabetical order
lowest numerical sequence: first point of
difference rule
Dr. Wolf's CHM 201 & 202
22 - 3
Nomenclature
OH
OH
OH
OH
OH
OH
1,2-Benzenediol
1,3-Benzenediol
1,4-Benzenediol
(common name:
pyrocatechol)
(common name:
resorcinol)
(common name:
hydroquinone)
Dr. Wolf's CHM 201 & 202
22 - 4
Nomenclature
OH
p-Hydroxybenzoic acid
CO2H
name on basis of benzoic acid as parent
higher oxidation states of carbon outrank
hydroxyl group
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22 - 5
Structure and Bonding
Dr. Wolf's CHM 201 & 202
22 - 6
Structure of Phenol
phenol is planar
C—O bond distance is 136 pm, which is
slightly shorter than that of CH3OH (142 pm)
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22 - 7
Physical Properties
The OH group of phenols allows hydrogen bonding
to other phenol molecules and to water.
Dr. Wolf's CHM 201 & 202
22 - 8
Hydrogen Bonding in Phenols
O H
Dr. Wolf's CHM 201 & 202
O
22 - 9
Physical Properties (Table 24.1)
Compared to compounds of similar size and
molecular weight, hydrogen bonding in phenol
raises its melting point, boiling point, and
solubility in water.
Dr. Wolf's CHM 201 & 202
22 - 10
Physical Properties (Table 24.1)
C6H5CH3
C6H5OH
C6H5F
Molecular weight
92
94
96
Melting point (°C)
–95
43
–41
Boiling
point (°C,1 atm)
111
132
85
Solubility in
H2O (g/100 mL,25°C)
0.05
8.2
0.2
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22 - 11
Acidity of Phenols
most characteristic property of
phenols is their acidity
Dr. Wolf's CHM 201 & 202
22 - 12
Compare
••
•• O
•• –
•• O ••
H
Ka = 10-10
••
CH3CH2O
••
Dr. Wolf's CHM 201 & 202
+ +
H
Ka = 10-16
H
+ +
H
•• –
CH3CH2O ••
••
22 - 13
Delocalized negative charge in phenoxide ion
– ••
•• O ••
H
H
H
H
H
Dr. Wolf's CHM 201 & 202
22 - 14
Delocalized negative charge in phenoxide ion
– ••
•• O ••
••
•• O
H
H
H
H
H
H
H
Dr. Wolf's CHM 201 & 202
–
••
H
H
H
22 - 15
Delocalized negative charge in phenoxide ion
••
•• O
–
H
••
H
H
H
H
Dr. Wolf's CHM 201 & 202
22 - 16
Delocalized negative charge in phenoxide ion
••
••
•• O
H
H
••
–
H
Dr. Wolf's CHM 201 & 202
•• O
H
H
H
H
–
••
H
H
H
22 - 17
Delocalized negative charge in phenoxide ion
••
•• O
H
H
H
••
–
H
H
Dr. Wolf's CHM 201 & 202
22 - 18
Delocalized negative charge in phenoxide ion
••
••
•• O
H
H
••
–
H
Dr. Wolf's CHM 201 & 202
•• O
H
H
H
H
–
H
••
H
H
22 - 19
Phenols are converted to phenoxide ions
in aqueous base
••
•• O
•• –
•• O ••
H
–
+ HO
stronger acid
Dr. Wolf's CHM 201 & 202
+ H2O
weaker acid
22 - 20
Substituent Effects
on the
Acidity of Phenols
Dr. Wolf's CHM 201 & 202
22 - 21
Electron-releasing groups have little or no effect
OH
Ka:
1 x 10-10
Dr. Wolf's CHM 201 & 202
OH
OH
CH3
OCH3
5 x 10-11
6 x 10-11
22 - 22
Electron-withdrawing groups increase acidity
OH
Ka:
1 x 10-10
Dr. Wolf's CHM 201 & 202
OH
OH
Cl
NO2
4 x 10-9
7 x 10-8
22 - 23
Effect of electron-withdrawing groups is most
pronounced at ortho and para positions
OH
OH
OH
NO2
NO2
NO2
Ka:
6 x 10-8
Dr. Wolf's CHM 201 & 202
4 x 10-9
7 x 10-8
22 - 24
Effect of strong electron-withdrawing groups
is cumulative
OH
OH
OH
NO2
NO2
NO2
Ka: 7 x 10-8
1 x 10-4
Dr. Wolf's CHM 201 & 202
NO2
O2N
NO2
4 x 10-1
22 - 25
Resonance Depiction
– ••
•• O ••
••
•• O ••
H
H
H
H
H
H
H
H
•O
•
••
N
+
Dr. Wolf's CHM 201 & 202
••
O ••
•• –
••
•O
–• ••
N
+
••
O ••
•• –
22 - 26
Sources of Phenols
Phenol is an important industrial chemical.
Major use is in phenolic resins for adhesives
and plastics.
Annual U.S. production is about 4 billion
pounds per year.
Dr. Wolf's CHM 201 & 202
22 - 27
Industrial
Preparations
of Phenol
SO3H
1. NaOH
heat
2.
H+
Dr. Wolf's CHM 201 & 202
Cl
1. NaOH 2. H+
heat
OH
CH(CH3)2
1. O2
2. H2O
H2SO4
22 - 28
Laboratory Synthesis of Phenols
from arylamines via diazonium ions
O2N
NH2
1. NaNO2,
H2SO4,
H2O
O2N
OH
2. H2O, heat
(81-86%)
Dr. Wolf's CHM 201 & 202
22 - 29
Naturally Occurring Phenols
Many phenols occur naturally
Dr. Wolf's CHM 201 & 202
22 - 30
Example: Thymol
OH
CH3
CH(CH3)2
Thymol
(major constituent of oil of thyme)
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22 - 31
Example: 2,5-Dichlorophenol
OH
Cl
Cl
2,5-Dichlorophenol
(from defensive secretion of
a species of grasshopper)
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22 - 32
Reactions of Phenols:
Electrophilic Aromatic
Substitution
Hydroxyl group strongly activates the ring
toward electrophilic aromatic substitution
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22 - 33
Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
Dr. Wolf's CHM 201 & 202
22 - 34
Halogenation
OH
OH
+ Br2
ClCH2CH2Cl
0°C
Br
(93%)
monohalogenation in nonpolar solvent
(1,2-dichloroethane)
Dr. Wolf's CHM 201 & 202
22 - 35
Halogenation
OH
OH
+ 3Br2
F
H2O
Br
Br
25°C
F
Br
(95%)
multiple halogenation in polar solvent
(water)
Dr. Wolf's CHM 201 & 202
22 - 36
Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
Dr. Wolf's CHM 201 & 202
22 - 37
Nitration
OH
OH
NO2
HNO3
acetic acid
5°C
CH3
OH group controls
regiochemistry
Dr. Wolf's CHM 201 & 202
CH3
(73-77%)
22 - 38
Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
Dr. Wolf's CHM 201 & 202
22 - 39
Nitrosation
NO
OH
OH
NaNO2
H2SO4, H2O
0°C
(99%)
only strongly activated
rings undergo nitrosation
when treated with nitrous
acid
Dr. Wolf's CHM 201 & 202
22 - 40
Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
Dr. Wolf's CHM 201 & 202
22 - 41
Sulfonation
OH
H3C
OH
CH3
H2SO4
H3C
CH3
100°C
SO3H
OH group controls
regiochemistry
Dr. Wolf's CHM 201 & 202
(69%)
22 - 42
Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
Dr. Wolf's CHM 201 & 202
22 - 43
Friedel-Crafts Alkylation
OH
OH
CH3
CH3
(CH3)3COH
H3PO4
60°C
H3C
(CH3)3COH reacts
with H3PO4 to give
(CH3)3C+
Dr. Wolf's CHM 201 & 202
C CH3
CH3
(63%)
22 - 44
Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
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22 - 45
Acylation of Phenols
Acylation can take place either on the ring
by electrophilic aromatic substitution or on
oxygen by nucleophilic acyl substitution
Dr. Wolf's CHM 201 & 202
22 - 46
Friedel-Crafts Acylation
OH
OH
O
CH3CCl
+
ortho isomer
AlCl3
under Friedel-Crafts
conditions, acylation
of the ring occurs
(C-acylation)
Dr. Wolf's CHM 201 & 202
O
C
CH3
(74%)
(16%)
22 - 47
O-Acylation
O
OH
OC(CH2)6CH3
O
+ CH3(CH2)6CCl
(95%)
in the absence of AlCl3, acylation of the
hydroxyl group occurs (O-acylation)
Dr. Wolf's CHM 201 & 202
22 - 48
O- versus C-Acylation
O
OH
OC(CH2)6CH3
AlCl3
formed faster
O
C
(CH2)6CH3
more stable
O-Acylation is kinetically controlled process; C-acylation
is thermodynamically controlled
AlCl3 catalyzes the conversion of the aryl ester to the
aryl alkyl ketones; this is called the Fries rearrangement
Dr. Wolf's CHM 201 & 202
22 - 49
Carboxylation of Phenols
O
Aspirin and
the
Kolbe-Schmitt
Reaction
OCCH3
COH
O
Dr. Wolf's CHM 201 & 202
22 - 50
Aspirin is prepared from salicylic acid
O O
OH
COH
CH3COCCH3
H2SO4
O
O
OCCH3
COH
O
how is salicylic acid prepared?
Dr. Wolf's CHM 201 & 202
22 - 51
Preparation of Salicylic Acid
ONa
CO2
125°C, 100 atm
OH
CONa
O
called the Kolbe-Schmitt reaction
acidification converts the sodium salt shown
above to salicylic acid
Dr. Wolf's CHM 201 & 202
22 - 52
What Drives the Reaction?
acid-base considerations provide an explanation:
stronger base on left; weaker base on right
•• •–
O•
••
+
••
O
H
C
•• •–
O•
••
••
CO2
•• O •
•
stronger base:
pKa of conjugate
acid = 10
Dr. Wolf's CHM 201 & 202
weaker base:
pKa of conjugate
acid = 3
22 - 53
Preparation of Salicylic Acid
ONa
CO2
OH
125°C, 100 atm
CONa
O
how does carbon-carbon bond form?
recall electron delocalization in phenoxide ion
negative charge shared by oxygen and by the
ring carbons that are ortho and para to oxygen
Dr. Wolf's CHM 201 & 202
22 - 54
– ••
•• O ••
••
•• O
H
H
H
H
H
H
••
H
••
••
•• O
–
••
H
H
Dr. Wolf's CHM 201 & 202
H
H
H
H
H
H
H
•• O
H
–
H
••
–
H
H
22 - 55
Mechanism of ortho Carboxylation
•• ••
O
•• –•
O•
••
H
Dr. Wolf's CHM 201 & 202
C
O ••
••
•• •
O•
C
H
•• •–
O•
••
•• O •
•
22 - 56
Mechanism of ortho Carboxylation
•• ••
O
•• –•
O•
••
•• •
O•
C
O ••
••
C
H
••
O
H
C
•• •–
O•
••
••
Dr. Wolf's CHM 201 & 202
H
•• O •
•
•• •–
O•
••
•• O •
•
22 - 57
Why ortho?
Why not para?
••
O
H
C
•• •–
O•
••
••
•• O •
•
Dr. Wolf's CHM 201 & 202
•• •–
O•
••
••
O
••
–• ••
•O
••
H
C
•• O •
•
22 - 58
Why ortho?
Why not para?
••
O
H
C
•• •–
O•
••
••
•• O •
•
•• •–
O•
••
••
O
••
–• ••
•O
••
H
C
•• O •
•
stronger base:
weaker base:
pKa of conjugate acid = 3 pKa of conjugate acid = 4.5
Dr. Wolf's CHM 201 & 202
22 - 59
Intramolecular Hydrogen Bonding
in Salicylate Ion
O
H
C
O–
O
Hydrogen bonding between carboxylate and hydroxyl
group stabilizes salicylate ion. Salicylate is less basic
than para isomer and predominates under conditions
of thermodynamic control.
Dr. Wolf's CHM 201 & 202
22 - 60
Preparation of Aryl Ethers
Dr. Wolf's CHM 201 & 202
22 - 61
Typical Preparation is by Williamson Synthesis
ONa + RX
Dr. Wolf's CHM 201 & 202
SN2
OR + NaX
22 - 62
Typical Preparation is by Williamson Synthesis
ONa + RX
SN2
OR + NaX
but the other combination
X + RONa
fails because aryl halides are normally unreactive
toward nucleophilic substitution
Dr. Wolf's CHM 201 & 202
22 - 63
Example
acetone
ONa + CH3I
heat
OCH3
(95%)
Dr. Wolf's CHM 201 & 202
22 - 64
Example
OH
K2CO3
+ H2C
acetone, heat
OCH2CH
Dr. Wolf's CHM 201 & 202
CHCH2Br
(86%)
CH2
22 - 65
Aryl Ethers from Aryl Halides
F
OCH3
+ KOCH3
NO2
CH3OH
+ KF
25°C
NO2
(93%)
nucleophilic aromatic substitution is effective
with nitro-substituted (ortho and/or para) aryl
halides
Dr. Wolf's CHM 201 & 202
22 - 66
Cleavage of Aryl Ethers
by Hydrogen Halides
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22 - 67
Cleavage of Alkyl Aryl Ethers
Ar
•• •
O• + H
R
Dr. Wolf's CHM 201 & 202
••
Br ••
••
•• –
•• Br • +
•
••
Ar
••
+O
H
R
22 - 68
Cleavage of Alkyl Aryl Ethers
Ar
•• •
O• + H
•• –
•• Br • +
•
••
••
Br ••
••
R
Ar
••
+O
H
R
An alkyl halide is
formed; never an
aryl halide!
R
Dr. Wolf's CHM 201 & 202
Ar
••
Br ••
••
+
••
O
••
H
22 - 69
Example
OCH3
OH
HBr
heat
OH
+ CH3Br
OH
(85-87%)
Dr. Wolf's CHM 201 & 202
(57-72%)
22 - 70
Claisen Rearrangement
of Allyl Aryl Ethers
Dr. Wolf's CHM 201 & 202
22 - 71
Allyl Aryl Ethers Rearrange on Heating
OCH2CH
CH2
200°C
allyl group
migrates to
ortho position
OH
CH2CH
CH2
(73%)
Dr. Wolf's CHM 201 & 202
22 - 72
Mechanism
OCH2CH
CH2
O
rewrite as
OH
keto-to-enol
isomerization
O
H
Dr. Wolf's CHM 201 & 202
22 - 73
Sigmatropic Rearrangement
Claisen rearrangement is an example of a
sigmatropic rearrangement. A  bond migrates
from one end of a conjugated  electron system
to the other.
this  bond breaks
O
O
“conjugated 
electron system”
is the allyl group
H
this  bond forms
Dr. Wolf's CHM 201 & 202
22 - 74
Oxidation of Phenols:
Quinones
Dr. Wolf's CHM 201 & 202
22 - 75
Quinones
The most common examples of phenol oxidations
are the oxidations of 1,2- and 1,4-benzenediols
to give quinones.
OH
O
Na2Cr2O7, H2SO4
H2O
OH
O
(76-81%)
Dr. Wolf's CHM 201 & 202
22 - 76
Quinones
The most common examples of phenol oxidations
are the oxidations of 1,2- and 1,4-benzenediols
to give quinones.
OH
O
OH
O
Ag2O
diethyl ether
CH3
CH3
(68%)
Dr. Wolf's CHM 201 & 202
22 - 77
Some quinones are dyes
O
OH
OH
O
Alizarin
(red pigment)
Dr. Wolf's CHM 201 & 202
22 - 78
Some quinones are important biomolecules
O
CH3
CH3O
CH3O
n
O
Ubiquinone (Coenzyme Q)
n = 6-10
involved in biological electron transport
Dr. Wolf's CHM 201 & 202
22 - 79
Some quinones are important biomolecules
O
CH3
CH3
O
CH3
CH3
CH3
CH3
Vitamin K
(blood-clotting factor)
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22 - 80
Spectroscopic Analysis of Phenols
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22 - 81
Infrared Spectroscopy
infrared spectra of phenols combine features
of alcohols and aromatic compounds
O—H stretch analogous to alcohols near
3600 cm-1
C—O stretch at 1200-1250 cm-1
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22 - 82
Figure 24.3: Infrared Spectrum of p-Cresol
CH3
C—H
OH
C—O
O—H
3500
3000
2500
2000
1500
1000
500
Wave number, cm-1
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22 - 83
1H
NMR
Hydroxyl proton of OH group lies between alcohols
and carboxylic acids; range is ca.  4-12 ppm
(depends on concentration). For p-cresol the OH
proton appears at  5.1 ppm (Figure 24.4).
H
H
CH3
HO
H
Dr. Wolf's CHM 201 & 202
H
22 - 84
H
H
HO
CH3
H
10.0
9.0
8.0
7.0
6.0
H
5.0
4.0
3.0
2.0
1.0
0
Chemical shift (, ppm)
Dr. Wolf's CHM 201 & 202
22 - 85
13C
NMR
OH
155.1
112..3
116.1
139.8
129.4
121.7
CH3 21.3
Oxygen of hydroxyl group deshields carbon
to which it is directly attached.
The most shielded carbons of the ring are those that
are ortho and para to the oxygen.
Dr. Wolf's CHM 201 & 202
22 - 86
UV-VIS
Oxygen substitution on ring shifts max to longer
wavelength; effect is greater in phenoxide ion.
OH
O
max
max
max
204 nm
210 nm
235 nm
256 nm
270 nm
287 nm
Dr. Wolf's CHM 201 & 202
–
22 - 87
Mass Spectrometry
Prominent peak for molecular ion. Most intense
peak in phenol is for molecular ion.
•+
OH
••
m/z 94
Dr. Wolf's CHM 201 & 202
22 - 88
End of Chapter 22
Dr. Wolf's CHM 201 & 202
22 - 89