LSW S04
Exam 2
Phenols
Nomenclature:
Functional group suffix =
Functional group prefix =
OH
OH
Cl
Cl
Cl
Physical Properties:
melting point:
boiling point:
aqueous solubility:
O
H
OH
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OH
LSW S04
Exam 2
Structure:
OH
Reactivity:
a) Nucleophilicity:
b) Acidity:
O
Carboxylic acids
Phenols
Alcohols
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Exam 2
Purification and acidity:
Briefly describe how p-methylbenzoic acid, p-ethylphenol
and 2-phenyl-1-ethanol could be separated by extraction.
Substituent Effects
e- withdrawing: (EWG)
e- donating: (EDG)
o-nitrophenol:
O
O
O
N
N
O
Compound
Phenol
O
pKa
O
Compound
o-Methoxyphenol
p-Methoxyphenol
o-Methylphenol
p-Methylphenol
o-Chlorophenol
o-Nitrophenol
p-Chlorophenol
p-Nitrophenol
m-Nitrophenol
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pKa
LSW S04
Exam 2
Draw the resonance structures for the following:
p-nitrophenoxide:
O
O
O
O
N
N
O
O
O
O
O
N
N
O
O
O
O
N
O
O
O
O
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N
O
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Exam 2
m-nitrophenoxide:
O
O
N O
N
O
O
O
O
N
O
O
N
O
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O
LSW S04
Exam 2
Preparation of Phenols:
Benzene
sulfonic acid
Chlorobenzene
SO3H
+ NaOH
Heat
OH
Work up
with acid
Cl
+ NaOH
OH
Heat
Work up
with acid
Acidic
oxidation
cumene
+ O2
OH
H2O
H2SO4
+
Diazonium
salts
N2
H2SO4
+ H2O
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heat
OH
+
N2
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Exam 2
i) Basic Hydrolysis of Benzene sulfonic acid
SO3H
Heat
+ NaOH
OH
Reaction type:
Reagents:
Leaving Group:
Prepare phenol from benzene:
270
(Via benzenesulfonic acid)
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Exam 2
ii) Basic Hydrolysis of Chlorobenzene
Work up
with acid
Cl
Heat
+ NaOH
OH
Reaction type:
Reagents:
Problems:
Make phenol from benzene via chlorobenzene.
iii) Acidic Oxidation of Cumene
OOH
OH
H2O
+ O2
H2SO4
Reaction type:
Reagents:
Mechanism:
Advantage:
Make phenol from benzene through cumene.
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Exam 2
iv) Preparation of Phenols from Aryl Diazonium Salts
+
N2
H2SO4
+ H2O
OH
+
N2
heat
Reaction type:
Leaving Group:
Reagents:
Mechanism:
Advantage:
Produce phenol from benzene using an aryldiazonium salt.
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Exam 2
Reactions of Phenols:
OH
E
i) EAS
OH
+
OH
E
+
a) Nitration
b) Sulfonation
+
+ H
E
c) Halogenation
para
d) Alkylation
ortho
Electrophiles: (E)
e) Acylation
a) NO2
f) Nitrosation
d) ROH + H
b) SO3
c) X= Cl, Br, I
e) RCOCl
f) NaNO2/ HCl
+
or RCl AlCl3
ii) Acylation
a)
OH
OH
a) carbon
O
+
R
AlCl3
LG
O
LG = I, Br, Cl, R
b) oxygen
R
O
O
b)
O
OH
O
+
R
O
LG
LG = I, Br, Cl,R
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O
O
R
LSW S04
iii) Carboxylation
Exam 2
ONa 1. CO / 125oC
2
100 atm
OH
2. H+
-
OH
B
iv) Aryl Ethers
CO2H
O
-
OR
RX
OH
O
OH
O
Ag2O
ether
OR
v) Oxidation
OH
O
Na2Cr2O7
H2SO4(aq)
OH
274
O
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Exam 2
Electrophilic Aromatic Substitution
OH
E
OH
+
OH
E
+
+
+
H
E
para
ortho
Reaction type:
Reaction
a) Nitration
b) Sulfonation
Phenol
dil. HNO3 in
H2O or
CH3CO2H
conc. H2SO4
c) Halogenation
X2
d) Alkylation
ROH / H+ or
RCl / AlCl3
RCOCl / AlCl3
aq. NaNO2 / H+
e) Acylation
f) Nitrosation
Problems:
275
Benzene
HNO3 /
H2SO4
H2SO4 or
SO3 / H2SO4
X2 / Fe or
FeX3
RCl / AlCl3
RCOCl / AlCl3
LSW S04
Exam 2
ii) Acylation of Phenols
O
OH
OH
O
R
Carbon Acylation
Cl
R
Oxygen Acylation
O
O
R
Phenols are bidentate nucleophiles:
a) Carbon acylation
OH
OH
O
+
R
AlCl3
LG
O
LG = I, Br, Cl, R
O
R
O
Reaction type:
Reagents:
b) Oxygen-acylation
OH
O
O
+
O
R
LG
O
LG = I, Br, Cl, R
O
Reaction type:
Reagents:
Acid catalyzed:
Base catalyzed:
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R
LSW S04
Exam 2
iii) Carboxylation of Phenols (Kolbe-Schmitt reaction)
ONa
1. CO2/ 125oC 100 atm
OH
CO2H
2. H+
Reaction type:
Reagents:
Regiochemistry:
Advantage:
O
H
C O
OH
O
OH
+
-
B
C
O
B
-
Make aspirin (acetyl salicylic acid) from phenol.
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LSW S04
Exam 2
OH
iv) Preparation of Aryl Ethers
OH
B
-
-
O
Reaction type:
Reagents: 1)
2)
Limitations:
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RX
OR
LSW S04
Exam 2
v) Oxidation of Phenols
OH
OH
O
OH Ag O
2
ether
O
O
Na2Cr2O7
OR
H2SO4(aq)
OH
O
Reaction type:
Reagents: a)
b)
Limitations:
Importance:
Mechanism for the oxidation of hydroquinone to benzoquinone:
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LSW S04
Exam 2
E) Reactions of Aryl Ethers
O
R
O
Electrophilic
Aromatic
Substitution
E
R
O
+
+
R
E
+
+
H
E
C
Cleavage of
Aryl Ethers by
HX
O
OH Br
+
+
HX
C
X = I, Br
Claisen
Rearrangment
of Aryl and
Allyl Ethers
OH
O
Heat
280
LSW S04
Exam 2
i) Electrophilic Aromatic Substitution
O R
+
R
E
O
E
O
R
E
+
+
+
H
Reaction type:
Regioselectivity:
Advantage:
Problem:
ii) Cleavage of Aryl Ethers by HI or HBr
O
C
OH
+
HX
+
X = I, Br
Reaction type:
Reagents:
Leaving group:
Mechanism:
O
Br
O
O
What about
?
281
C
LSW S04
Exam 2
iii) Claisen Rearrangment of Aryl Allyl Ethers:
O
OH
heat
Reaction type :
Mechanism:
O
XII. Spectroscopy of Alcohols, Ethers and Phenols
A) IR
Absorbance
Interpretation ROH Ether
(cm-1)
3600 (strong,
broad)
> 3000
2800-2900
1600
1200-1250
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Phenol
LSW S04
Exam 2
1
B) H NMR
Resonance Interpretation ROH Ether Phenol
(ppm)
4-12
(exchange)
1.0 – 3.0
3.3- 4.0
7-8
(exchangeable means that the peak "disappears" when shaken with D2O)
C)
13
C NMR
Resonance Interpretation ROH Ether Phenol
(ppm)
20-60
Alkyl C
60-90
120-150
Alkyl C-O
aromatic
carbons, ArC
ArC-O
o- and p- C
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LSW S04
Exam 2
D) UV-VIS
Alcohols and Ethers:
Phenols:
E) Mass Spectrometry
Alcohols and Ethers:
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