Chapter 15: Reactions of Substituted Benzenes
Learning Objectives:
1. Be able to recognize and utilize the oxidative and reductive reactions involving the substituents on benzene. 2. Recognize whether a substituent on a benzene ring is activating or deactivating toward electrophilic aromatic substitution reaction, and why it is so. 3. Predict the effect a substituent will have on the regioselectivity of an electrophilic substitution reaction. 4. Predict the effect a substituent will have on p Ka . 5. Be able to design the synthesis of a multisubstituted benzene. 6. Be able to recognize and utilize the reactions involving arenediazonium salts. 7. Recognize and be able to write the mechanism of nucleophilic aromatic substitution. 8. Recognize the structure of benzyne, be able to explain how it is formed, and how it reacts.
Sections:
15.1 Nomenclature of Disubstituted and Polysubstituted Benzenes 15.2 Some Substituents Increase the Reactivity of a Benzene Ring and Some Decrease Its Reactivity* 15.3 The Effect of Substituents on Orientation (Regioselectivity)* 15.4 The Effect Substituent on p Ka 15.5 The Ortho-Para ratio 15.6 Additional Considerations Regarding Substituent Effects 15.7 Designing a Synthesis III: Synthesis of monosubstituted and Disubstituted Benzenes* 15.8 Synthesis of Trisubstituted Benzenes 15.9 Synthesis of Substituted Benzenes Using Arenediazonium Salts* 15.10 The Arenediazonium Ion as an Electrophile* 15.11 Mechanism for the Reaction of Amines with Nitrous Acid* 15.12 Nucleophilic Aromatic Substitution Reactions: An Addition-Elimination Mechanism* 15.13 Nucleophilic Aromatic Substitution Reactions: An Elimination-Addition Mechanism That Forms a Benzyne Intermediate 15.14 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
Br H2N
NO2 NO2
Br Br NO2 Br OH CH3
Cl
Br Br CH3 NO Br NH2 2
Cl 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 NH2 OH
Moderate activating groups (substituents)
O O
HN R O R
4 Weak activating groups (substituents)
R
Weak deactivating groups (substituents)
F Cl Br I
5 Moderate deactivating groups (substituents)
H O H O R O OR O N R
6 Strong deactivating groups (substituents)
SO3H NO2 CN NR3
7 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 Br2 (1 equivalent) FeCl3
OR Br2 (excess) FeCl3
9 (v)
NH2 CH3COCl AlCl3
O
HN R 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 p Ka
I II III IV V VI OH OH OH OH OH OH
CHO NO CH Cl 2 OCH3 3
I II III IV V VI CO H CO2H CO2H CO H CO2H 2 CO2H 2
CHO NO CH Br 2 OCH3 3
II IV V VI I III NH NH NH NH3 3 3 NH3 3 NH3
CH Br CHO NO2 OCH3 3
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
NaNO2, HCl 0oC R NH2 RN N Cl
diazonium salt
Mechanism:
16 B. Reaction of arenediazonium salt with nucleophiles
Sandmeyer reation (CuBr, CuCl, and CuCN)
+ Reaction with KI, HBF 4, H 3O , and H 3PO 2
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 (S NAr): An Addition-Elimination Mechanism*
A. Comparison of S NAr, S N1, and S N2
B. General mechanism
19 C. Examples
(i)
Cl OH
OH
NO2 NO2
Cl OH
NO2 NO2 OH
NO2 NO2
Cl OH
O2N NO2 O2N NO2 OH
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