Chapter 16: 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:
16.1 Nomenclature of Disubstituted and Polysubstituted Benzenes 16.2 Reactions of Substituents on Benzene 16.3 The Effect of Substituents on Reactivity* 16.4 The Effect of Substituents on Orientation (Regioselectivity)* 16.5 The Effect Substituent on p Ka 16.6 The Ortho-para ratio 16.7 Additional Considerations Regarding Substituent Effects 16.8 Designing a Synthesis III: Synthesis of monosubstituted and Disubstituted Benzenes* 16.9 Synthesis of Trisubstituted Benzenes 16.10 Synthesis of Substituted Benzenes Using Arenediazonium Salts* 16.11 The Arenediazonium Ion as an Electrophile* 16.12 Mechanism for the Reaction of Amines with Nitrous Acid* 16.13 Nucleophilic Aromatic Substitution Reactions* 16.14 Benzyne 16.15 Polycyclic Benzenoid Hydrocarbons # 16.16 Electrophilic Substitution Reactions of Naphthalene and Substituted Naphthalene #
* Sections that will be focused # Sections that will be skipped
Recommended additional problems
16.36 – 6.41, 6.43 – 6.55, 6.57 – 6.60, 6.62 – 6.68
1 Class Note
16.1 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 16.2 Reactions of Substituents on Benzene
A. Reactions of Alkyl Substituents
tert-BuO
Br NBS OH peroxide
or hν
CN
3
H2, Pt
N H2, Pt
H2, Pt O
B. Oxidations of Alkyl Substituents
1. KMnO4, heat (reflux) 2. H+
+ Na2Cr2O7, H , heat
4
+ Na2Cr2O7, H , heat
+ Na2Cr2O7, H , heat
+ Na2Cr2O7, H , heat
OH MnO2 (no heating needed)
OH + Na2Cr2O7, H , heat
5 C. Reduction of Nitro Group
NO2 H2, Pt
NO2 Sn, HCl
NO2 Fe, HCl
16.3 The Effect of Substituents on Reactivity and 16.4 The Effect of Substituents on Orientation (Regioselectivity) electron donation group (EDG) electron withdrawing group (EWG)
EDG EWG
6 A. Relative rate of electrophilic aromatic substitution
Examples:
OCH3 NO2
• Rate-determining step (r.d.s) • Resonance effect and inductive effect
7 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
8 Weak activating groups (substituents)
R
Weak deactivating groups (substituents)
F Cl Br I
9 Moderate deactivating groups (substituents)
H O H O R O OR O N R
10 Strong deactivating groups (substituents)
SO3H NO2 CN NR3
11 C. Examples (combined with 16.6 The Ortho-para ratio and 16.7 Additional Considerations Regarding Substituent Effects)
(i)
CH3
Br2, FeCl3
(ii)
CH3 HNO3 H2SO4
CH2CH3 HNO3 H2SO4
C(CH3)3 HNO3 H2SO4
12 (iii)
Br
Cl2, FeCl3
(iv)
OR Br2 (1 equivalent) FeCl3
OR Br2 (excess) FeCl3
13 (v)
NH2 CH3COCl AlCl3
O
HN R CH3COCl AlCl3
(vi)
O R HNO3 H2SO4
NO2 HNO3 H2SO4
14 (vii) Synthesis of trinitrotoluene
CH3 HNO3 H2SO4
15 16.5 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
16 16.8 Designing a Synthesis III: Synthesis of monosubstituted and Disubstituted Benzenes and 16.9 Synthesis of Trisubstituted Benzenes
Design multiple-step synthesis:
* Selectivity: chemoselectivity , regioselectivity , and stereoselectivity * Retrosynthetic analysis: breaking and formation of chemical bonds
17 A. Examples
(i)
OH
from
18 (ii) O CH3
from
O2N
(iii) O CH3
from
NO2
19 16.12 Mechanism for the Reaction of Amines with Nitrous Acid and 16.10 Synthesis of Substituted Benzenes Using Arenediazonium Salts
A. Formation of diazonium salt
NaNO2, HCl 0oC R NH2 RN N Cl
diazonium salt
Mechanism:
20 B. Reaction of arenediazonium salt with nucleophiles
Sandmeyer reation (CuBr, CuCl, and CuCN)
+ Reaction with KI, HBF 4, H 3O , and H 3PO 2
21 16.11 The Arenediazonium Ion as an Electrophile
N
N
Nu
* Nucleophile better be bulky * Terminal nitrogen reacts with nucleophile
22 16.13 Nucleophilic Aromatic Substitution (S NAr) Reactions
A. Comparison of S NAr, S N1, and S N2
B. General mechanism
23 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
24 16.14 Benzyne
25