Chapter 15: Reactions of Substituted Benzenes
Learning Objectives:
1.
2.
3.
4.
5.
6.
7.
8.
Be able to recognize and utilize the oxidative and reductive reactions involving the
substituents on benzene.
Recognize whether a substituent on a benzene ring is activating or deactivating
toward electrophilic aromatic substitution reaction, and why it is so.
Predict the effect a substituent will have on the regioselectivity of an electrophilic
substitution reaction.
Predict the effect a substituent will have on pKa.
Be able to design the synthesis of a multisubstituted benzene.
Be able to recognize and utilize the reactions involving arenediazonium salts.
Recognize and be able to write the mechanism of nucleophilic aromatic substitution.
Recognize the structure of benzyne, be able to explain how it is formed, and how it
reacts.
Sections:
15.1
15.2
15.3
15.4
15.5
15.6
15.7
15.8
15.9
15.10
15.11
15.12
15.13
15.14
Nomenclature of Disubstituted and Polysubstituted Benzenes
Some Substituents Increase the Reactivity of a Benzene Ring and Some
Decrease Its Reactivity*
The Effect of Substituents on Orientation (Regioselectivity)*
The Effect Substituent on pKa
The Ortho-Para ratio
Additional Considerations Regarding Substituent Effects
Designing a Synthesis III: Synthesis of monosubstituted and Disubstituted
Benzenes*
Synthesis of Trisubstituted Benzenes
Synthesis of Substituted Benzenes Using Arenediazonium Salts*
The Arenediazonium Ion as an Electrophile*
Mechanism for the Reaction of Amines with Nitrous Acid*
Nucleophilic Aromatic Substitution Reactions: An Addition-Elimination
Mechanism*
Nucleophilic Aromatic Substitution Reactions: An Elimination-Addition
Mechanism That Forms a Benzyne Intermediate
Polycyclic Benzenoid Hydrocarbons#
* Sections that will be focused
#
Sections that will be skipped
Recommended additional problems
15.34 – 15.69
1
Class Note
15.1
Nomenclature of Disubstituted and Polysubstituted Benzenes
Br
Br
H2N
Br
NO2
NO2
Br
NO2
Br
OH
Br
CH3
Cl
Br
Br
CH3
Cl
NO2
NH2
Br
Cl
Cl
2
15.2
Some Substituents Increase the Reactivity of a Benzene Ring and Some
Decrease Its Reactivity* and 15.3 The Effect of Substituents on Orientation
(Regioselectivity)*
electron donation group (EDG)
electron withdrawing group (EWG)
EDG
EWG
A. Relative rate of electrophilic aromatic substitution
Examples:
OCH3


NO2
Rate-determining step (r.d.s)
Resonance effect and inductive effect
3
B. Relative reactivity and regioselectivity of substituted benzenes
Strong activating groups (substituents)
OR
OH
NH2
Moderate activating groups (substituents)
O
O
HN
R
O
R
4
Weak activating groups (substituents)
R
Weak deactivating groups (substituents)
F
Cl
Br
5
I
Moderate deactivating groups (substituents)
O
H
O
R
O
6
OR
O
H
N
R
Strong deactivating groups (substituents)
SO3H
NO2
CN
7
NR3
C. Examples (combined with 15.5 The Ortho-Para ratio and 15.6 Additional
Considerations Regarding Substituent Effects)
(i)
CH3
Br2, FeCl3
(ii)
CH3
HNO3
H2SO4
CH2CH3
HNO3
H2SO4
C(CH3)3
HNO3
H2SO4
8
(iii)
Br
Cl2, FeCl3
(iv)
OR
OR
Br2 (1 equivalent)
FeCl3
Br2 (excess)
FeCl3
9
(v)
NH2
CH3COCl
AlCl3
O
R
HN
CH3COCl
AlCl3
(vi)
O
R
HNO3
H2SO4
NO2
HNO3
H2SO4
10
(vii) Synthesis of trinitrotoluene
CH3
HNO3
H2SO4
11
15.4
The Effect Substituent on pKa
V
I
II
III
IV
OH
OH
OH
OH
OH
OH
CH3
Cl
CHO
OCH3
NO2
I
II
III
IV
CO2H
CO2H
CO2H
CO2H
CO2H
CO2H
CH3
Br
CHO
OCH3
NO2
I
II
V
VI
NH3
NH3
OCH3
CH3
IV
III
V
VI
VI
NH3
NH3
NH3
Br
CHO
NO2
NH3
12
15.7
Designing a Synthesis III: Synthesis of monosubstituted and Disubstituted
Benzenes* and 15.8 Synthesis of Trisubstituted Benzenes
Design multiple-step synthesis:
* Selectivity: chemoselectivity, regioselectivity, and stereoselectivity
* Retrosynthetic analysis: breaking and formation of chemical bonds
13
A. Examples
(i)
OH
from
14
(ii)
O
CH3
from
O2N
(iii)
O
CH3
from
NO2
15
15.9
Synthesis of Substituted Benzenes Using Arenediazonium Salts and 15.11
Mechanism for the Reaction of Amines with Nitrous Acid*
A. Formation of diazonium salt
R
NH2
NaNO2, HCl
0oC
R
N
N
Cl
diazonium salt
Mechanism:
16
B. Reaction of arenediazonium salt with nucleophiles
Sandmeyer reation (CuBr, CuCl, and CuCN)
Reaction with KI, HBF4, H3O+, and H3PO2
17
15.10
The Arenediazonium Ion as an Electrophile*
N
N
Nu
* Nucleophile better be bulky
* Terminal nitrogen reacts with nucleophile
18
15.12
Nucleophilic Aromatic Substitution Reactions (SNAr): An Addition-Elimination
Mechanism*
A. Comparison of SNAr, SN1, and SN2
B. General mechanism
19
C. Examples
(i)
Cl
OH
OH
NO2
NO2
Cl
OH
NO2
NO2
OH
NO2
NO2
Cl
OH
O2N
NO2
OH
O2N
NO2
NO2
NO2
(ii)
Br
NHCH2CH3
NO2
NO2
CH3CH2NH2
then OH
NO2
NO2
20
15.13
Nucleophilic Aromatic Substitution Reactions: An Elimination-Addition
Mechanism That Forms a Benzyne Intermediate
21