Transcript File

Phenols
Dr Md Ashraful Alam
Ar-OH
Phenols are compounds with an –OH
group attached to an aromatic carbon.
Although they share the same functional
group with alcohols, where the –OH group
is attached to an aliphatic carbon, the
chemistry of phenols is very different from
that of alcohols.
Nomenclature.
Phenols are usually named as substituted phenols. The
methylphenols are given the special name, cresols. Some
other phenols are named as hydroxy compounds.
CH3
OH
OH
OH
OH
COOH
Br
phenol
m-bromophenol
OH
OH
o-cresol
salicylic acid
OH
COOH
OH
OH
OH
OH
catechol
resorcinol
hydroquinone
p-hydroxybenzoic acid
Physical properties
The crystals are hygroscopic and turn pink to red in air
phenols are polar and can hydrogen bond
phenols are water insoluble
phenols are stronger acids than water and will dissolve
in 5% NaOH
phenols are weaker acids than carbonic acid and (do
not dissolve in 5% NaHCO3 )
 Phenol:
◦ is poisonous, corrosive, and flammable.
◦ affects the central nervous system and targets the liver
and kidneys.
◦ is mutagenic and possibly teratogenic.
Intramolecular hydrogen bonding is possible in some
ortho-substituted phenols.
This intramolecular
hydrogen bonding reduces water solubility and
increases volatility. Thus, o-nitrophenol is steam
distillable while the isomeric p-nitrophenol is not.
OH
O
N
O
H
O
o-nitrophenol
bp 100oC at 100 mm
0.2 g / 100 mL water
volatile with steam
NO2
p-nitrophenol
bp decomposes
1.69 g / 100 mL water
non-volatile with steam
Routes of Exposure: Absorption
 All forms of phenol cause irritation, and acute
toxic effects of phenol most often occur by skin
contact. Even dilute solutions (1 to 2%) may
cause severe burns if contact is prolonged.
 Due to its local anesthetizing properties, skin
burns may be painless.
 Phenol vapor and liquid penetrate the skin
readily.
 Systemic poisoning effects follow skin
absorption.
• Discoloration and severe burns may occur, but
may be disguised by a loss of pain sensation.
6
Routes of Exposure: Products Containing
Phenol
 Phenol, in low doses, can be found in some consumer
products. It is used as a disinfectant, antiseptic and pain
reliever
 Mostly used in the manufacture of resins and plastics, but it
is also found in explosives, fertilizers, paints rubber,
textiles, adhesives, drugs, paper, soap, wood preservatives
and photographic developers.
7
Synthesis of Phenols
Synthesis of Phenols
Synthesis of Phenols
Phenols
be prepared
by the
hydrolysis
of arenediazonium
salts:
Phenols
maymay
be prepared
by the
hydrolysis
of arenediazonium
salts:
Phenols may be prepared by the hydrolysis of arenediazonium salts:
Ar-NH2
Ar-NH2
Cu2O
[HONO]
+ Ar-OH
ArN
X
Cu2O
[HONO]
2+
Ar-OH
HX
ArN2 X- Cu2+,2+H2O
an
areneCu , H2O
HX
an
arenediazonium salt
diazonium salt
Sinceofboth
of the above
steps involve
mild conditions,
most
Since both
the
above
steps
involve
mild
conditions,
most
substituted
Since both
of the
above
steps involve
mild
conditions, most
substituted
phenols
can
be
prepared
by
the
procedure.
phenols
can be prepared
substituted
phenols by
canthe
be procedure.
prepared by the procedure.
EXAMPLE:
EXAMPLE:
EXAMPLE:
NH2
NH2
diazotization
diazotization
[HONO]
[HONO]
HCl
HCl
Br
Br
+
N2+Cl- N2 Cl
Br
Br
hydrolysis
hydrolysis
OH
OH
Cu2O
Cu2O
Cu(NO3)2, H2O
Cu(NO3)2, H2O
Br
Br
p-Bromophenol
p-Bromophenol
(95%)
(95%)
Industrial Syntheses of Phenol
Industrial Syntheses of Phenol
Phenol is important
in the production
of aspirin
soaps, aspirin
and
Phenol is important
in the production
of soaps,
and plastics.
Annual
production
in the United
than
4
Annualplastics.
production
in the
United States
is moreStates
thanis4 more
billion
pounds.
billion
pounds.
There aresyntheses
several commercial
syntheses for phenol.
There are
several
commercial
for phenol.
Alkali fusion of sodium benzenesulfonate
Alkali fusion
sodium
benzenesulfonate
Thisof
first
commercial
synthesis was introduced in Germany in
This first
commercial
synthesis
was
introduced
in Germany
in 1890 and
1890
and later in
the United
States
as demand
grew for phenol
because
of the
success
of Bakelite,
a polymer
of phenol
andof the
later in the
United
States
as demand
grew
for phenol
because
formaldehyde.
success of
Bakelite, a polymer of phenol and formaldehyde.
O- Na+
O=S=O
O- Na+
NaOH
350
Sodium
benzenesulfonate
O- Na+
oC
Sodium
phenoxide
+ Na2SO3 + H2O
Sodium
sulfite
OH
H 3O +
Phenol
Process
(1924)
The The
DowDow
Process
(1924)
An improved electrochemical synthesis provided a relatively
An improved
electrochemical
provided
a relatively
source
cheap source
of chlorine synthesis
(Cl2) early
in the 20th
century,cheap
and this
of chlorine
(Cl2)aearly
in theof20th
this permitted
a variation
permitted
variation
the century,
original and
commercial
synthesis
of
of thephenol
original
synthesis of phenol to be developed.
to commercial
be developed.
O- Na+
Cl
NaOH
350
oC,
+ NaCl + H2O
pressure
Chlorobenzene
O- Na+
OH
H3O+
Phenol
Oxidation
of Cumene
(Isopropylbenzene)
Oxidation
of Cumene
(Isopropylbenzene)
This process, originally developed in Germany in 1944, is the
This process, originally developed in Germany in 1944, is the preferred
preferred way to produce phenol commercially. For each pound of
way to phenol
produce
phenol commercially. For each pound of phenol produced,
produced, 0.6 pound of acetone (another important industrial
0.6 pound
of acetone (another important industrial chemical) is produced.
chemical) is produced. The overall industrial process begins with two
The overall
industrialbenzene
process
with two petrochemicals: benzene
petrochemicals:
andbegins
propene.
and propene.
H+
+
CH3CH=CH2
O2
CH
CH3 CH3
Isopropylbenzene
(cumene)
C-OOH
CH3 CH3
Cumene
hydroperoxide
H3O+/H2O
OH
=
O
+ CH3CCH3
Acetone
Phenol
Synthesis of Cumene: Acid-Catalyzed Alkylation of Benzene
Synthesis of Cumene: Acid-Catalyzed Alkylation of Benzene
This synthesis is carried out under conditions that minimize the
This synthesis
is carried out under conditions that minimize the
polyalkylation
of benzene:
polyalkylation of benzene:
CH3CH=CH2
H3PO4
oC,
250
pressure
+
CH3CHCH3
+
H CH(CH3)2
(- H+)
Cumene
CH
H3C CH3
Sources of Phenols, Synthesis
13
From aryl diazonium ion
From aryl ketones
Naturally Occurring Phenols. Phenols are common in nature.
resveratrol
 -tocopherol (vitamin E)
14
Resonance of Phenolate ion
O
O
O
O
O
Substituents that stabilize an anion enhance the acidity of pheno
Phenol has a pKa = 10; p-nitrophenol has a pKa = 7.1
Picric acid (2,4,6-trinitrophenol)
• 2,4,6-trinitrophenol is so acidic that it is called picric
acid; it has a Ka = 10-1 (pKa =1)
• The enhanced acidity compared to phenol itself (Ka =
10-10) is due to the increased resonance stabilization of
the conjugate base (phenolate anion) by the nitro
groups:
O
O
N
O
O
O
N
O
O
O
N
O
Phenols as Acids
Phenolsas
asAcids
Acids
Phenols
Phenols
are
much
Phenolsare
aremuch
muchmore
more
Phenols
more
RCOH
2H
RCO
acidic
than
alcohols,
but
acidic
than
alcohols,
but
2
acidic than alcohols, but
are
weaker
acids
areweaker
weakeracids
acidsthan
than
pKa
4-5
are
than
pK
4-5
a
carboxylic
acids.
carboxylicacids.
acids.
carboxylic
ArOH
ArOH
ROH
ROH
<11
<11
~18
~18
Theseacidities
aciditiesare
areexplained
explainedin
terms
the
different
stabilities
ofthe
the
These
acidities
are
explained
of
the
different
stabilities
ofof
the
These
ininterms
terms
ofof
the
different
stabilities
－-) of the acids (HA) that influence the equilibrium:
conjugate
bases
(A:
conjugate
bases
(A:
theacids
acids(HA)
(HA)that
thatinfluence
influencethe
theequilibrium:
equilibrium:
conjugate bases (A: ) ofofthe
HA ++ HHO
O
HA
22
KK
aa
-O
A:
+ +++ A:
3
HH
O
3
-]-]
[HO
O
] [A:
++
3
[H
]
[A:
= 3
a
KK
=
a
[HA]
[HA]
- drives the equilibrium
An
increase
in
the
stability
of
A:
An increase in the stability of A: drives the equilibrium
An increase
intoto
the
stability
ofincreasing
A:－ drives
the
equilibrium
more
more
the
right,increasing
the
magnitude
K.a. to the right,
more
the
right,
the
magnitude
ofofK
a
increasing the magnitude of Ka.
An Example:
Example: Cyclohexanol
Cyclohexanoland
andPhenol
Phenol
An
An Example: Cyclohexanol and Phenol
OH
OH
OH
OH
Phenol
a much
is is
a much
Phenol is aPhenol
much
stronger
acid than
stronger
stronger acid
than acid than
cyclohexanol.
cyclohexanol.
cyclohexanol.
Phenol
Phenol
9.89
9.89
Cyclohexanol
Cyclohexanol
pKpKa 1818
a
This difference in acidity is understandable in terms of the
This difference
in acidity
is understandable
in terms
of the
This difference
in acidity
is understandable
in terms
of the
difference in
difference
in
stabilities
of
the
conjugate
bases.
The
conjugate
base
difference
in
stabilities
of
the
conjugate
bases.
The
conjugate
base
stabilities
of the conjugate
bases. anion.
The conjugate
base
of cyclohexanol is a
of
cyclohexanol
is
a localized
There
is
no
resonance
of
cyclohexanol
is
a
localized
anion.
There
is
no
resonance
localized
anion. There
is
no resonance
through
a series
of resonance
stabilization.
The
conjugate
base
phenol
may
represented
stabilization.
The
conjugate
base
ofof
phenol
may
bebe
represented
structures
that
show
itresonance
is
a delocalized
anion.
The
hybrid
is
through
a series
resonance
structures
that
show
astructure
delocalized
through
a series
ofof
structures
that
show
it it
is is
a delocalized
stabilized
resonance.
anion.by
The
hybrid
structure
stabilized
resonance.
anion.
The
hybrid
structure
is is
stabilized
byby
resonance.
:
:
-
:O:
:O:
:
:
-:O:
:O:
: :
:O:O
:O:
:O:
-..-..
:
--
:
Resonance
structures
phenoxide
ion
Resonance
structures
forfor
thethe
phenoxide
ion
:O:
:O:
..- ..-
Carboxylic
Acids
and
Phenols:
Solubilities
Carboxylic
Acids
and
Phenols:
Solubilities
Carboxylic
Acids
and
Phenols:
Solubilities
A standard
way
separate
water-insoluble
carboxylic
acids
and
A standard
way
to separate
water-insoluble
carboxylic
acids
and
A standard
way
to to
separate
water-insoluble
carboxylic
acids
and
phenols
phenols
is
by
extraction
with
an
aqueous
solution
of
sodium
phenols is by
extraction
with an
aqueousofsolution
sodium
is by extraction
with
an aqueous
solution
sodiumofbicarbonate.
bicarbonate.
Carboxylic
acidsacids
are soluble
in theinaqueous
phasephase
bicarbonate.
Carboxylic
soluble
the aqueous
Carboxylic
acids
are
soluble
in
theare
aqueous
phase
through
their salts,
through
theirtheir
salts,salts,
whilewhile
the less
phenols
remain
in thein the
through
theacidic
less acidic
phenols
remain
while the less acidic phenols remain in the organic phase. Relative acidities:
organic
phase.
Relative
acidities:
organic
phase.
Relative
acidities:
RCO2RCO
H +2HNa++ HCO
Na+ 3HCO3stronger
stronger
stronger stronger
base base
acid acid
=
=
O O
RCORCO
HOCOH ArOH
ArOH
2H 2HHOCOH
Consider the following
4-5a 4-5
6.4 6.4
~10 ~10
pKequilibria:
a pK
Consider
the following
equilibria:
Consider
the following
equilibria:
- Na+- + + H CO
RCO2RCO
+
H32CO3
2
2 Na
weaker
weaker weaker
weaker
base base
acid acid
waterwater
soluble
soluble
ArOHArOH
+ Na++ HCO
Na+ 3HCO3weaker
weaker
weaker weaker
base base
acid acid
ArO-ArO
Na+- Na
++ H2+COH32CO3
stronger
stronger stronger
stronger
base base
acid acid
water
soluble
watercarboxylic
soluble
selectively deprotonate
acids in
Bicarbonate ion will
the
Bicarbonate
ion will
selectively
carboxylic
acidsacids
in thein the
Bicarbonate
ion because
will
selectively
carboxylic
presence
of phenols
ofdeprotonate
the deprotonate
above equilibria.
presence
of phenols
because
of theofabove
equilibria.
presence
of phenols
because
the above
equilibria.
Separation of Phenols and Alcohols
Separation of Phenols and Alcohols
Mixtures of water-insoluble phenols and alcohols may be separated by
Mixtures of water-insoluble phenols and alcohols may be
extraction with an aqueous solution of hydroxide ion. Because of the
separated by extraction with an aqueous solution of hydroxide ion.
greater acidity of the phenols, they rapidly react with hydroxide ions to
Because of the greater acidity of the phenols, they rapidly react
produce
water-soluble phenoxide ions.
with hydroxide ions to produce water-soluble phenoxide ions.
Relative acidities:
pKa
ArOH
HOH
ROH
~10
15.7
~18
Consider the equilibria:
ArOH
+
stronger
acid
ROH +
weaker
acid
Na+ -OH
stronger
base
Na+ -OH
weaker
base
ArO- Na+ + H2O
weaker
weaker
base
acid
water soluble
RO- Na+ + H2O
stronger stronger
acid
base
water soluble
Hydroxide
ion will deprotonate
phenols
selectively
in the
of most
Hydroxide
ion will deprotonate
phenols
selectively
in presence
the
presence
of most
alcohols.
With the exception
methanol,
alcohols.
With the
exception
of methanol,
alcoholsofare
slightly less acidic
alcohols are slightly less acidic than water.
than water.
Phenols, reactions
1. as acids
2. ester formation
3. ether formation
4. EAS
a) nitration
b) coupling with diaz salts
c) halogenation
d) Friedel-Crafts alkylation
as acids:
with active metals:
OH
ONa
Na
+ H2(g)
sodium phenoxide
with bases:
CH4 < NH3 < HCCH < ROH < H2O < phenols < H2CO3 < RCOOH < HF
ONa
OH
+ NaOH
SA
SB
+ H2O
WB
WA
2. ester formation (similar to alcohols)
OH
CH3
O
+ CH3CH2C
OH
H+
O
CH3CH2C
O
H3C
O
H3C C
OH
COOH
O
COOH
+ (CH3CO)2O
salicyclic acid
aspirin
+ H2O
Reactions of Phenols
Reactions
Phenols
Reactions
of of
Phenols
Acylation of the Hydroxyl Group
Acylationof
of the
the Hydroxyl
Group
Acylation
Hydroxyl
Group
general procedures:
O O
OH + RCOCR
O O
acid anhydride
OH + RCOCR
acid anhydride
O
OH + RCCl
acyl chloride
O
OH + RCCl
acyl chloride
base
base
base
base
=
=
O
O
Acylation
is introduction
the introduction
acylgroup,
group, RCAcylation
is the
of of
thethe
acyl
Acylation
is
the
introduction
of
the
acylby
group,
RCThe
hydroxyl
group
in
phenols
may
be
acylated
either
of two
The hydroxyl
group
ininphenols
may
be be
acylated
by either
of two
The
hydroxyl
group
phenols
may
acylated
by
either
of two
general
procedures:
general procedures:
O
O
OCR + RCOH
O
O
OCR + RCOH
O
OCR + HCl
O
OCR + HCl
3. ether formation (Williamson Synthesis)
Ar-O-Na+ + R-X  Ar-O-R + NaX
note: R-X must be 1o or CH3
Because phenols are more acidic than water, it is possible
to generate the phenoxide using NaOH.
OCH2CH3
OH
+ CH3CH2Br, NaOH
CH3
CH3
Phenols
SynthesisofofEthers
Ethers
Phenolsin
inthe
the Williamson
Williamson Synthesis
Because ofBecause
their acidity
are easily
converted
of their(pK
acidity
(pKaphenols
~10), phenols
are easily
convertedinto
into their
a~10),
phenoxide
ions
with sodium
orsodium
potassium
hydroxide.
The nucleophilic
their
phenoxide
ions with
or potassium
hydroxide.
The
nucleophilic
phenoxide
ions halides
react with
alkyl
halides (orcompounds)
equivalent
phenoxide
ions react
with alkyl
(or
equivalent
by an
compounds)
by an aryl
SN2 mechanism
to yield aryl alkyl ethers.
SN2 mechanism
to yield
alkyl ethers.
ArOH
HO-
RX
ArO-
ArOR
(where X = Cl, Br, I
phenoxide
or OSO2R or OSO2OR)
ion
: :
: :
via Ar-O:
C X:
All the usual structural limitations of
the SN2 mechanism apply.
Examples
O- Na+
OH
NaOH
OCH3
CH3I
+ NaI
= =
= =
Br
Br
Br
Sodium
p-Bromoanisole
p-Bromophenol
p-bromophenoxide
OCH3
O
O
CH3OSOCH3
+ Na+ -OSOCH3
O
O
(Dimethyl sulfate)
Br
p-Bromoanisole
Cleavage of Aryl Alkyl Ethers
Cleavage of Aryl Alkyl Ethers
Reaction
these
ethers
in ainspecific
direction:
Reactionwith
withHI
HIororHBr
HBrcleaves
cleaves
these
ethers
a specific
direction:
fast and reversible protonation
:
: :
O-CH3 + H-Br
H
+
O-CH3 + Br-
better leaving group
cleavage by nucleophilic attack
: :
:
H
+
O-CH3 + Br-
OH + CH3Br
Nucleophilic
attackdoes
doesnot
notoccur
occuronon
aromatic
ring.
Nucleophilic attack
thethe
aromatic
ring.
4. Electrophilic Aromatic Substitution
The –OH group is a powerful activating group in EAS
and an ortho/para director.
a) nitration
OH
OH
HNO3
O2N
NO2
polynitration!
NO2
OH
OH
OH
dilute HNO3
NO2
+
NO2
b) halogenation
OH
OH
Br2 (aq.)
Br
Br
no catalyst required
use polar solvent
polyhalogenation!
Br
OH
OH
OH
Br2, CCl4
Br
+
non-polar solvent
Br
c) Friedel-Crafts alkylation.
OH
OH
+
CH3
H3C C CH3
Cl
AlCl3
H3C C CH3
CH3
d) Friedel-Crafts acylation
f) coupling with diazonium salts
(EAS with the weak electrophile diazonium)
N2 Cl
OH
OH
CH3
CH3
+
benzenediazonium
chloride
an azo dye
N
N
g) Kolbe reaction (carbonation)
OH
ONa
+ CO2
COONa
125oC, 4-7 atm.
sodium salicylate
H+
EAS by the weakly
electrophilic CO2

O C O
OH
COOH
salicylic acid
h) Reimer-Tiemann reaction
OH
OH
CHCl3, aq. NaOH
H+
CHO
70oC
salicylaldehyde
The salicylaldehyde can be easily oxidized to salicylic acid
Quiz 1
Quiz 21.01
The order of acidity (strongest to weakest) of the oxygen acids below is
The order of acidity (strongest to weakest) of the oxygen acids
below is
COOH
OH
OH
OH
NO2
I
II
III
I > IV > III > II
IV
Quiz 2
Quiz 21.02
Provide the structures of the products of the reactions below.
Provide the structures of the products of the reactions below.
O
OCCH3
=
OH
=
O
+ CH3CCl
Et3N as base
OH
OH
+ Br2
CH3
Br
0
oC,
CCl4
CH3
Quiz 3
Quiz 21.03
Provide the
missing
in the scheme
below.below.
Provide
thestructures
missing structures
in the scheme
NH2
OH
(1) NaNO2, HBr, H2O, 0 oC
(2) Cu2O, Cu(NO3)2, H2O
CH3
CH3
(1) CO2, pressure;
then heat
(2) H3O+
OH
COOH
CH3
Quiz
4 21.04
Quiz
Ar-Cl
Quiz 21.04
NaOCH3
Ar-OCH3
CH3OH
NaOCH3
In a nucleophilic
reaction like that abo
Ar-Cl aromatic substitution
Ar-OCH3
CH3OH
In awhich
nucleophilic
substitution
reaction
like that
of thearomatic
aryl chlorides
below
would
be above,
the most reactive?
which of
aryl chlorides
below
would bereaction
the most
reactive?
Inthe
a nucleophilic
aromatic
substitution
like
that above,
which of the aryl chlorides below would
Clbe the most reactive?
Cl
NO2
Cl
Cl
Cl
Cl
NO2
H3CH3C
CH
CH
3 3
I
I
O2 N O 2 N
II
NO2
II
NO2
NO2
III
NO2
III
Quiz 5 Quiz 21.05
Provide Provide
the structures
for thefor
key
andand
thethe
product(s) in the
the structures
theintermediate
key intermediate
reactionsproduct(s)
below. in the reaction below.
Br
CH3
CH3
KNH2
liq NH3
CH3
CH3
NH2
H2N
CH3
CH3
+
CH3
CH3