Transcript Organic Chemistry Fifth Edition

Chapter 22
Phenols
22.1
Nomenclature
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
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)
Nomenclature
OH
p-Hydroxybenzoic acid
CO2H
name on basis of benzoic acid as parent
higher oxidation states of carbon outrank
hydroxyl group
22.2
Structure and Bonding
Structure of Phenol
Phenol is planar.
C—O bond distance is 136 pm, which is
slightly shorter than that of CH3OH (142 pm).
22.3
Physical Properties
The OH group of phenols allows hydrogen bonding
to other phenol molecules and to water.
Hydrogen Bonding in Phenols
O H
O
Physical Properties (Table 22.1)
Compared to compounds of similar size and
molecular weight, hydrogen bonding in phenol
raises its melting point, boiling point, and
solubility in water.
Physical Properties (Table 22.1)
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
22.4
Acidity of Phenols
Most characteristic property of
phenols is their acidity.
Compare
••
•• O
•• –
•• O ••
H
pKa = 10
H
••
CH3CH2O
••
pKa = 16
H
+ +
•• –
+ + CH CH O
•
H
3
2 •
••
Delocalized negative charge in phenoxide ion
– ••
•• O ••
••
•• O
H
H
H
H
H
H
H
–
••
H
H
H
Delocalized negative charge in phenoxide ion
••
••
•• O
H
H
••
–
H
•• O
H
H
H
H
–
••
H
H
H
Delocalized negative charge in phenoxide ion
••
••
•• O
H
H
••
–
H
•• O
H
H
H
H
–
H
••
H
H
Phenols are converted to phenoxide ions
in aqueous base
••
•• O
•• –
•• O ••
H
–
+ HO
stronger acid
+ H2O
weaker acid
22.5
Substituent Effects
on the
Acidity of Phenols
Electron-releasing groups have little or no effect
OH
pKa:
10
OH
OH
CH3
OCH3
10.3
10.2
Electron-withdrawing groups increase acidity
OH
pKa:
10
OH
OH
Cl
NO2
9.4
7.2
Effect of electron-withdrawing groups is most
pronounced at ortho and para positions
OH
OH
OH
NO2
NO2
NO2
pKa:
7.2
8.4
7.2
Effect of strong electron-withdrawing groups
is cumulative
OH
OH
OH
NO2
NO2
pKa:
7.2
NO2
4.0
NO2
O2N
NO2
0.4
Resonance Depiction
– ••
•• O ••
••
•• O ••
H
H
H
H
H
H
H
H
•• O
••
N
+
••
O ••
•• –
••
•• O
– ••
N
+
••
O ••
•• –
22.6
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.
Industrial
Preparations
of Phenol
SO3H
1. NaOH
heat
2. H+
1. NaOH
heat
Cl
2. H+
OH
CH(CH3)2
1. O2
2. H2O
H2SO4
Laboratory Synthesis of Phenols
from arylamines via diazonium ions
O2N
NH2
1. NaNO2,
H2SO4,
H2O
O2N
OH
2. H2O, heat
(81-86%)
22.7
Naturally Occurring Phenols
Many phenols occur naturally.
Example: Thymol
OH
CH3
CH(CH3)2
Thymol
(major constituent of oil of thyme)
Example: 2,5-Dichlorophenol
OH
Cl
Cl
2,5-Dichlorophenol
(from defensive secretion of
a species of grasshopper)
22.8
Reactions of Phenols:
Electrophilic Aromatic
Substitution
Hydroxyl group strongly activates the ring
toward electrophilic aromatic substitution.
Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
Halogenation
OH
OH
+ Br2
ClCH2CH2Cl
0°C
Br
(93%)
monohalogenation in nonpolar solvent
(1,2-dichloroethane)
Halogenation
OH
OH
+ 3Br2
F
H2O
Br
Br
25°C
F
Br
(95%)
multiple halogenation in polar solvent
(water)
Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
Nitration
OH
OH
NO2
HNO3
acetic acid
5°C
CH3
OH group controls
regiochemistry.
CH3
(73-77%)
Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
Nitrosation
NO
OH
OH
NaNO2
H2SO4, H2O
0°C
(99%)
Only strongly activated
rings undergo nitrosation
when treated with nitrous
acid.
Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
Sulfonation
OH
H3C
OH
CH3
H2SO4
H3C
CH3
100°C
SO3H
OH group controls
regiochemistry.
(69%)
Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
Friedel-Crafts Alkylation
OH
OH
CH3
CH3
(CH3)3COH
H3PO4
60°C
H3C
(CH3)3COH reacts
with H3PO4 to give
(CH3)3C+.
C CH3
CH3
(63%)
Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
22.9
Acylation of Phenols
Acylation can take place either on the ring
by electrophilic aromatic substitution or on
oxygen by nucleophilic acyl substitution.
Friedel-Crafts Acylation
OH
OH
O
CH3CCl
+
ortho isomer
AlCl3
Under Friedel-Crafts
conditions, acylation
of the ring occurs
(C-acylation).
O
C
CH3
(74%)
(16%)
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).
O- versus C-Acylation
O
OH
OC(CH2)6CH3
AlCl3
C
formed faster
CH3
O
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.
22.10
Carboxylation of Phenols:
Aspirin and the Kolbe-Schmitt Reaction
O
OCCH3
COH
O
Aspirin is prepared from salicylic acid
O O
OH
COH
CH3COCCH3
H2SO4
O
How is salicylic acid prepared?
O
OCCH3
COH
O
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.
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
weaker base:
pKa of conjugate
acid = 3
Preparation of Salicylic Acid
ONa
CO2
125°C, 100 atm
OH
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
– ••
•• O ••
••
•• O
H
H
H
H
H
H
••
H
••
••
–
••
H
H
H
H
H
•• O
•• O
H
–
H
H
H
H
H
••
–
H
H
Mechanism of ortho Carboxylation
••
•• O
•• –•
O•
••
•• •
O•
C
O ••
••
C
H
••
H
O
H
C
•• •–
O•
••
••
• O•
• •
•• •–
O•
••
• O•
• •
Why ortho?
Why not para?
••
O
H
C
•• •–
O•
••
••
•• O •
•
weaker base:
pKa of conjugate acid = 3
•• •–
O•
••
••
O
••
–• ••
•O
••
H
C
•• O •
•
stronger base:
pKa of conjugate acid = 4.5
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.
22.11
Preparation of Aryl Ethers
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
Example
ONa + CH3I
acetone
heat
OCH3
(95%)
Example
OH
K2CO3
+ H2C
CHCH2Br
acetone, heat
OCH2CH
CH2
(86%)
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.
22.12
Cleavage of Aryl Ethers
by Hydrogen Halides
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
Ar
••
Br ••
••
+
••
O
••
H
Example
OCH3
OH
HBr
heat
OH
+ CH3Br
OH
(85-87%)
(57-72%)
22.13
Claisen Rearrangement
of Allyl Aryl Ethers
Allyl Aryl Ethers Rearrange on Heating
OCH2CH
CH2
Allyl group
200°C
migrates to
ortho position.
OH
CH2CH
(73%)
CH2
Mechanism
OCH2CH
CH2
O
rewrite as
OH
keto-to-enol
isomerization
O
H
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.
22.14
Oxidation of Phenols:
Quinones
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%)
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%)
Some quinones are dyes
O
OH
OH
O
Alizarin
(red pigment)
Some quinones are important biomolecules
O
CH3
CH3O
CH3O
n
O
Ubiquinone (Coenzyme Q)
n = 6-10
involved in biological electron transport
Some quinones are important biomolecules
O
CH3
CH3
O
CH3
CH3
CH3
Vitamin K
(blood-clotting factor)
CH3
Section 22.15
Spectroscopic Analysis of Phenols
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
Figure 22.3: Infrared Spectrum of p-Cresol
Francis A. Carey, Organic Chemistry, Fourth Edition. Copyright © 2000 The McGraw-Hill Companies, Inc. All rights reserved.
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 22.4).
H
H
CH3
HO
H
H
Figure 22.4
13C
NMR
OH
128.5
OCH3
155.1
121.1
159.7
115.5
114.0
129.8
129.5
120.7
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.
UV-VIS
Oxygen substitution on ring shifts max to longer
wavelength; effect is greater in phenoxide ion.
OH
max
204 nm
256 nm
max
210 nm
270 nm
O
max
235 nm
287 nm
–
Mass Spectrometry
Prominent peak for molecular ion. Most intense
peak in phenol is for molecular ion.
•+
OH
••
m/z 94