CH. 22
Chapter 22 Phenols
Nomenclature
The –OH group takes precedence as the parent phenol.
OH
OH
phenol
6
meta-cresol
CH3
Cl
5
OH
1
4
CH3
2
3
5-chloro-2-methylphenol
Carboxyl and acyl groups take precedence over the –OH group.
O
C OH
p-hydroxybenzoic acid
HO
The –OH group is a strong electron-donating group through the lone pair.
O H
O H
O H
Phenol can hydrogen bond with H2O and other phenol groups.
H O
H
O H
O
H
H O
b.p. 132 °C
H
1
O H
Ortho-nitrophenol can engage in intramolecular hydrogen bonding and has a lower boiling
point and lower water solubility than either the meta or para-isomers because there is less
intermolecular hydrogen bonding and less hydrogen bonding with water.
O
H
N
O
intramolecular
hydrogen bond
O
H
H
O
H O
O
O
N
ortho-nitrophenol
O
N
O
H O
H
O
para-nitrophenol
H
Phenols are much more acidic than regular alcohols. It is completely deprotonated by
sodium hydroxide.
CH3CH2
O H + Na
OH
CH3CH2
+
O
H2O
Keq ~ 1
pKa 16
O
H + Na
O
+
OH
Keq 105.7
H2O
pKa 15.7
pKa ~10
This is due to the fact that the resulting anion is stabilized by resonance donation of the
lone pair onto the benzene ring.
O
O
O
O
But it is not a strong enough acid to be significantly ionized by sodium bicarbonate.
O
H
+
O
O
O
+
Na+ -O C OH
HO C OH
pKa ~6
pKa 10
This allows separation of a mixture of phenol, benzoic acid and toluene in diethyl ether
using simple acid-base chemistry. The mixture is first treated with a solution of aqueous
sodium bicarbonate. This is will deprotonate the benzoic acid, making it soluble in the
2
aqueous layer, while phenol and toluene remain in the organic layer. The aqueous layer is
drained off, treated with mild acid to neutralize it and precipitate the benzoic acid as a solid
which can be recovered by filtration. The organic layer is then treated with sodium
hydroxide, a stronger base, which can deprotonate the phenol but not the toluene. The
phenol will be extracted into the aqueous layer where it can be separated from the organic
layer. Neutralization with dilute acid will reprotonate the phenol and it can be separated
from the aqueous layer extraction with diethyl ether. This just leaves the original organic
layer containing the toluene.
Add 1M
OH
O
O
OH
OH
CH3
Org
layer
NaO C OH
H2O
layer
O
O_ Na+
CH3
drain bottom aqueous
layer in separatory
funnel
in Et2O solution
O
OH
CH3
Org
layer
Add 1 M
NaOH
Add 1 M HCl
OH
filter
O
CH3
O_ Na+
O- Na+
Org
layer
H2O
layer
drain bottom aqueous
layer in separatory
funnel
OH
Add 1 M HCl
filter
O- Na+
Electron withdrawing groups on the phenol will increase the acidity and donating groups
will decrease the acidity.
3
Cl
CH3
O
O
H
pKa 10
O
H
pKa 8.6
pKa 10.3
NO2
NO2
H
O
pKa 7.2
O
H
O 2N
H
pKa 4.0
Reactions of Phenols
(1) Electrophilic Aromatic Substitution. Phenols are very reactive due to the electrondonation by the hydroxyl lone pair. For bromination, for example, no catalyst is needed
and it is hard to stop at mono-bromination. Like with aniline derivatives, the product is
usually the 2,4,6-tribromophenol.
OH
OH
Br2
Br
Br
25 °C
Br
To get mono-bromination, use low temperature. Usually the para-isomer is the major
product.
OH
OH
Br2
0 °C
Br
For nitration, nitric acid in water or acetic acid can be used. Sulfuric acid is not needed as
a dehydrating agent for the nitric acid. Oxidation of the benzene ring can be a major side
reaction.
OH
OH
OH
NO2
HNO3
+
H2O
NO2
4
Sulfonation gives mainly the para-isomer.
OH
OH
OH
SO3H
H2SO4
+
100 °C
minor
SO3H major
Friedel-Crafts alkylation gives mainly the para-isomer.
OH
OH
OH CH3
C CH3
(CH3)3CCl
+
CH3
AlCl3
CH3
minor
C CH3
CH3
major
Friedel-Crafts acylation also gives mainly the para-isomer.
OH
O
CH3CH2CH2
OH
OH
O
C
C Cl
+
AlCl3
O C CH CH CH
2
2
3
CH2CH3CH3
minor (16%)
major (74%)
So, in the presence of aluminum trichloride, we see acylation at carbon. In the absence of
aluminum trichloride, we see acylation at oxygen.
O
OH
O
CH3CH2CH2
O C CH2CH2CH3
C Cl
With anhydrides, acid activation is used and acylation also occurs on oxygen.
5
O
OH
O
CH3CH2
O
O C CH2CH3
O
C O C CH2CH3
+
H2SO4
HO C CH2CH3
Acylation can also be done in basic conditions with anhydrides. Treatment of the phenol
with sodium hydroxide deprotonates the phenol and makes the oxygen a better
nucleophile.
CH3CH2
O
OH
O
NaOH
CH3CH2
O
O C O
C O C CH2CH3
O
O
CH2CH3
O C CH2CH3
O
H2O
+
O
O C CH2CH3
Aryl Ethers
For synthesis of aryl ethers, the phenol must be the nucleophile since there is no
nucleophilic substitution at sp2 carbons.
O
OH
O
Br
NaOH
H2O
If there is a strong electron withdrawing group, nucleophilic aromatic substitution can
occur through an addition-elimination mechanism.
F
NO2
F
NaOCH3
HOCH3
OCH3
OCH3
NO2
NO2
Cleavage of aryl ethers occurs only on the alkyl side of the ether since there is no
nucleophilic substitution at sp2 carbons.
H
O CH2CH3
H Br
O CH2CH3
6
Br
H
O
+
CH3CH2Br