chapter 15: reactions of substituted benzenes learning...
TRANSCRIPT
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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 pKa.
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 pKa
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
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Class Note
15.1 Nomenclature of Disubstituted and Polysubstituted Benzenes
Br
Br
Br
NO2NO2
H2N
Br
OH
NO2
Br
Cl
Br
NO2
Cl
CH3
Br
Cl
Br
NH2
Cl
Br
CH3
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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)*
EDG EWG
electron donation group (EDG)
electron withdrawing group (EWG)
A. Relative rate of electrophilic aromatic substitution
Examples:
OCH3 NO2
• Rate-determining step (r.d.s)
• Resonance effect and inductive effect
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B. Relative reactivity and regioselectivity of substituted benzenes
Strong activating groups (substituents)
NH2 OH OR
Moderate activating groups (substituents)
HN O
O
R
O
R
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Weak activating groups (substituents)
R
Weak deactivating groups (substituents)
F Cl Br I
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Moderate deactivating groups (substituents)
O H O R O OR OHN
R
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Strong deactivating groups (substituents)
SO3H NO2 CN NR3
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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
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(iii)
Br
Cl2, FeCl3
(iv)
ORBr2 (1 equivalent)
FeCl3
ORBr2 (excess)
FeCl3
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(v)
NH2
HN
O
R
CH3COClAlCl3
CH3COClAlCl3
(vi)
O R
NO2
HNO3
H2SO4
HNO3
H2SO4
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(vii) Synthesis of trinitrotoluene
CH3
HNO3
H2SO4
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15.4 The Effect Substituent on pKa
OHOH
CH3
OH
OCH3
OH
CHO
OH
Cl
OH
NO2
I II III IV V VI
CO2HCO2H
CH3
CO2H
OCH3
CO2H
CHO
CO2H
Br
CO2H
NO2
I II III IV V VI
NH3NH3
CH3
NH3
OCH3
NH3
CHO
NH3
Br
NH3
NO2
I IIIII
IV V VI
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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
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A. Examples
(i)
from
OH
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(ii)
from
CH3O
O2N
(iii)
from
CH3
NO2
O
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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
0oCR N N Cl
diazonium salt
Mechanism:
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B. Reaction of arenediazonium salt with nucleophiles
Sandmeyer reation (CuBr, CuCl, and CuCN)
Reaction with KI, HBF4, H3O+, and H3PO2
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15.10 The Arenediazonium Ion as an Electrophile*
N
N
Nu
* Nucleophile better be bulky
* Terminal nitrogen reacts with nucleophile
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15.12 Nucleophilic Aromatic Substitution Reactions (SNAr): An Addition-Elimination
Mechanism*
A. Comparison of SNAr, SN1, and SN2
B. General mechanism
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C. Examples
(i)
Cl
NO2
Cl
NO2
Cl
NO2
NO2
NO2O2N
OH
OH
OH
OH
NO2
OH
NO2
OH
NO2
NO2
NO2O2N
(ii)
Br
NO2
NO2
NHCH2CH3
NO2
NO2CH3CH2NH2
then OH
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15.13 Nucleophilic Aromatic Substitution Reactions: An Elimination-Addition
Mechanism That Forms a Benzyne Intermediate