Alrasheed University College

Department of Pharmacy

Phenols
Lecture 3
Prepared by
Dr. Kutaiba Ibrahim Alzand
1. Structure and Nomenclature of Phenols
 Compounds that have a hydroxyl group directly attached
to a benzene ring are called phenols.
 Thus, phenol is the specific name for hydroxybenzene,
and it is the general name for the family of compounds
derived from hydroxybenzene:

Ch. 21 - 2
1. Structure and Nomenclature of Phenols
 Compounds that have a hydroxyl group attached to a
polycyclic benzenoid ring are chemically similar to phenols,
but they are called naphthols and phenanthrols. For
example:

OH
OH OH

Phenol 1-Naphthol 9-Phenanthrol

(-naphthol)

Ch. 21
Ch.-21
3
1A. Nomenclature of Phenols
 In many compounds phenol is the base name.
 The methylphenols are commonly called cresols

Cl CH3
NO2

OH OH
OH

4-Chlorophenol 2-Nitrophenol 3-Methylphenol

(p-chlorophenol) (o-nitrophenol) (m-cresol)

Ch. 21 - 4
 The benzenediols also have common names

OH OH OH
OH

OH
OH
1,2-Benzenediol 1,3-Benzenediol 1,4-Benzenediol
(catechol) (resorcinol) (hydroquinone)

Ch. 21 - 5
2. Naturally Occurring Phenols
O CO2CH3


OH
O
H NH3+
HO
L-Tyrosine Methyl salicylate
(oil of wintergreen)
OH
CH3 OH
OCH3
H

H H
HO
Eugenol Estradiol
(oil of cloves)
Ch. 21 - 6
3. Physical Properties of Phenols

OH CH3
 Phenols are able to form strong
intermolecular Hydrogen bonds,
and therefore have higher boiling
points than hydrocarbons of the
same molecular weight.
Phenol Toluene
 Phenols are also modestly soluble
in water because of their ability M.W. 94 92
to form strong hydrogen bonds
with water molecules.
B.P. (oC) 182 110

Ch. 21 - 7
4. Synthesis of Phenols
4A. Laboratory Synthesis
 The most important laboratory synthesis of phenols is by
hydrolysis of arenediazonium salts

NH2 N2 2+
OH
Cu2O, Cu
HONO H2O
R R R

e.g. NH2 OH

1. NaNO2, HCl, 0-5oC

2. Cu2O, Cu2+, H2O
Cl CH3 Cl CH3

Ch. 21 - 8
4B. Industrial Syntheses
 Several methods have been used to synthesize phenol
commercially
 Hydrolysis of chlorobenzene (Dow Process)
 In this process chlorobenzene is heated at 350 oC (under high
pressure) with aqueous sodium hydroxide. The reaction produces
sodium phenoxide, which, on acidification, yields phenol.

Cl O Na
2 NaOH
o
+ NaCl + H2O
350 C
high pressure

HCl

OH
+ NaCl

Ch. 21 - 9
 From cumene hydroperoxide
 The synthesis begins with the Friedel–Crafts alkylation of benzene with
propene to produce cumene (isopropylbenzene)
 Then cumene is oxidized to cumene hydroperoxide
 Finally, when treated with 10% sulfuric acid, cumene hydroperoxide
undergoes a hydrolytic rearrangement that yields phenol and acetone:

H3PO4
+
250oC (Cumene)
high pressure

O2
95-135oC

O OH
H3O+
+ o
O
50-90 C OH
(Cumene
hydroperoxide)
Ch. 21 - 10
 Mechanism
● Chain initiation
Step 1

H R
+ R H

Ch. 21 - 11
● Chain propagation
Step 2

O O
+ O O

Step 3

O O H
+

O O H
+

Ch. 21 - 12
 ● Chain propagation
H
O O H O O
+ H OH2 H

- H2O

H
O O H2O O
H

OH2
+
H +
- H3O
O O O HO
H Ch. 21 - 13
5. Reactions of Phenols as Acids
pKa pKa

OH 9.89 O 2N OH 7.15

NO2

H 3C OH 10.17 O 2N OH 3.96

NO2

Cl OH 9.20 O2N OH 0.38

NO2

Ch. 21 - 14
 OH OH

pKa 18 9.89

O O
H
+ H2O + H3O+

(NO resonance
stabilization)

Ch. 21 - 15
 O
O
H
+ H3O+

+ H2O

O O O

Ch. 21 - 16
Solved Problem 21.1
Rank the following compounds in order of increasing acidity.

Strategy and Answer: Alcohols are less acidic than phenols,

and phenols are less acidic than carboxylic acids. An electron-
withdrawing group increases the acidity of a phenol relative to
phenol itself. Thus the order of increasing acidity among these
examples is:
Cyclohexanol < phenol < 4-nitrophenol < benzoic acid.

Ch. 21 - 17
Practice Problem 21.1
Methylphenols (cresols) are less acidic than phenol itself. For
example,

This behavior is characteristic of phenols bearing electron-

releasing groups. Provide an explanation. Answer

Ch. 21 - 18
Answer
The inductive effect of an electron-releasing group (i.e., -CH3)
changes the charge distribution in the molecule so as to increase
the electron density of the ring and oxygen, causing the proton to
be held more strongly; it also destabilizes the phenoxide anion by
intensifying its negative charge. These effects make the
substituted phenol less acidic than phenol itself.

Electron-releasing –CH3 destabilizes the

anion more than the acid. pKa is
larger than for phenol.
Ch. 21 - 19
5B. Distinguishing and Separating
Phenols from Alcohols and
Carboxylic Acids
Question
 If you are given three unknown samples: one is
benzoic acid; one is phenol; and one is cyclohexyl
alcohol; how would you distinguish them by
simple chemical tests?
● Recall: acidity of
H H
O O O
H
O
> >
Ch. 21 - 20
 O O
H + Na OH + H2O
R O R O Na
(soluable in water)

O O Na
H
+ NaOH

(soluble in water)

O
H
+ NaOH No Reaction

(immiscible
with H2O)
Ch. 21 - 21
O O
H
O O Na
+ NaHCO3

+ CO2(g) + H2O
(gas evolved)

O
H
+ NaHCO3 No Reaction

O
H
+ NaHCO3 No Reaction

Ch. 21 - 22
6. Other Reactions of the O–H Group of Phenols

 Phenols react with carboxylic acid anhydrides and acid

chlorides to form esters.

O O

R O R
base

O
O
OH
O R
R Cl
base

Ch. 21 - 23
6A. Phenols in the Williamson Synthesis
 Phenols can be converted to ethers through the Williamson synthesis.
 Because phenols are more acidic than alcohols, they can be converted
to sodium phenoxides through the use of sodium hydroxide

OH O Na

NaOH
R R R X
(X = halides,
OR
OTs, OMs)

R
e.g.
OH O
1. NaOH

2. Br

Ch. 21 - 24
7. Cleavage of Alkyl Aryl Ethers
 When alkyl aryl ethers react with strong acids such as HI
and HBr, the reaction produces an alkyl halide and a
phenol.

O OH
R conc. HX
+ RX
heat
R R

e.g.
O OH
conc. HCl
+ Cl
heat

Ch. 21 - 25
8. Reactions of the Benzene Ring of Phenols
 Bromination
OH
Br Br
3 Br2
+ 3 HBr
OH H2O

Br (NO Lewis acid

OH
required for the
brominations)
Br2
o
+ HBr
CS2, 5 C

Br
Ch. 21 - 26
 Nitration
 Phenol reacts with dilute nitric acid to yield a mixture of
o- and p-nitrophenol
 Although the yield is relatively low (because of oxidation
of the ring), the ortho and para isomers can be
separated by steam distillation.

OH OH OH
NO2
20% HNO3
+
o
25 C

NO2
(30-40%) (15%)

Ch. 21 - 27
 Sulfonation
 Phenol reacts with concentrated sulfuric acid to yield mainly the
ortho-sulfonated product if the reaction is carried out at 25 oC and
mainly the para-sulfonated product at 100 8C.
OH
SO3H
conc. H2SO4
25oC
OH
conc. H2SO4
100oC

This is another example of

OH thermodynamic versus kinetic
control of a reaction
conc. H2SO4
100oC

SO3H Ch. 21 - 28
 Kolbe reaction

O Na OH
COOH
1. CO2
2. H3O+

(Salicylic acid)

Ch. 21 - 29
 ● Mechanism
Na O O
H O
O
C
C Na
O
O

tautomerization

H H
O OH O O

O H3O+ O
Na
Salicylic acid Sodium salicylate
Ch. 21 - 30
 O

OH O O O
COOH COOH O
R O R
+
CH3COOH OH

(Salicylic acid) Acetylsalicylic acid

(Aspirin)

Ch. 21 - 31
9. The Claisen Rearrangement
 Heating allyl phenyl ether to 200 oC effects an intramolecular reaction
called a Claisen rearrangement. The product of the rearrangement
is o-allylphenol:

OH O
1. NaH
Br
2.

200oC

OH

Ch. 21 - 32
 Via a [3,3] sigmatropic rearrangement
1
2 O O
1'

3 2'
3'
H
The reaction takes place through a
concerted rearrangement in which keto-enol
the bond between C3 of the allyl
tautomerization
group and the ortho position of the
benzene ring forms at the same time
that the carbon–oxygen bond of the OH
allyl phenyl ether breaks.

Ch. 21 - 33
 END OF CHAPTER 21 

Ch. 21 - 34