Transcript Chapter 1 Structure and Bonding

Chapter 16 Benzene Derivatives
I.
Activation and Deactivation of the benzene ring
A.
Overview
1) Many important compounds are disubstituted aromatic rings
COOH
O
CH3
2-acetyloxybenzoic acid
Aspirin
2)
3)
4)
H3C
O
O
O
HO
HO
N
H
N-(4-hydroxyphenyl)acetamide
Acetominophen
Ibuprofen
In the last chapter, we learned how electrophilic aromatic substitution adds single
substituents to benzene
In this chapter, we will learn how to control where the 2nd and 3rd substituent goes
on benzene
The first substituent controls where the others go:
a) Activator = electron donor, directs to ortho and para sites D
A
b) Deactivator = electron acceptor, directs to meta sites
B.
Activation and Deactivation
1. Two different effects determine how a substituent effects benzene
a. Induction
i. e- density transmitted through s-bonds
ii. Primarily determined by electronegativity
iii. Has an effect only over short distances
D
A
A = CF3, NR2, OR, X,
O
C
R
C N
O
O
N O
S
O
D=R
b.
Resonance
i. e- density transmitted through multiple resonance structures
ii. Involves p-bonds
iii. Can be over a fairly long range
iv. Strongest in charged systems
OH
2.
Resonance Donating Groups
a) Contains an electron pair adjacent to the ring to delocalize into the ring
b) May be counter to the inductive effect of the same group
D
D
c)
D
D
Overall effect of this type of substituents is the sum of induction/resonance
i. Overall Donating = --NR2, --OR
ii. Overall Accepting = --X
O
O
O
Resonance Accepting Groups
S
N O
C N
C R
O
a) Contains a resonance structure with a cation adjacent to the ring
b) Usually reinforces induction
A
A
A
A
A
B
B
B
B
B
3.
OH
4.
Donor/Acceptor Effects on Electrophilic Aromatic Substitution
a) Electrophilic aromatic substitution requires a benzene p-bond to attack an
X
electrophile
X
H
b)
c)
d)
Z
+
Z
H
If X is electron donating, the rate speeds up = Activated
If X is electron accepting, the rate slows down = Deactivated
X
Nitration rate examples: X
H
NO2+
NO2
X
= OH, CH3, H,
Rate = 1000, 25, 1,
II.
Cl, COOEt, CF3,
0.033, 0.0037, 2.6 x 10-5,
Inductive Effects on Benzene
A. Alkyl groups are activating,
ortho/para directors
NO2
6 x 10-8
CH3
CH3
CH3
CH3
Br
Br2
FeBr3
Br
40%
1%
Br
60%
1)
Mechanism:
CH3
CH3
CH3
E
H
+
E
ortho
CH3
CH3
E
H
E
+
-H
H
most stable
resonance form
CH3
CH3
CH3
E+
meta
E
E
H
CH3
CH3
CH3
E
H
CH3
H
CH3
E+
para
E H
E H
most stable
resonance form
E H
E
2)
B.
Important Points
a. CH3 is donating by induction
b. The ortho and para attacks stabilize the carbocation by having one resonance
form where the carbocation is next to CH3
c. The meta attack gives no stabilized resonance form
Inductively Withdrawing groups deactivate and direct toward meta positions
CF3
CF3
HNO3
only product
H2SO4
NO2
1)
Mechanism
CF3
CF3
E+
ortho
CF3
E
H
CF3
CF3
E
H
E
H
very poor
resonance form
+
-H
E
CF3
CF3
CF3
E+
meta
E
E
H
CF3
CF3
CF3
E
H
CF3
H
CF3
+
E
para
E H
2)
E H
very poor
resonance form
E H
Important Points
a) All attacks are destabilized, meta is the least
b) Ortho and para have poor resonance structure with (+) next to CF3
c) Attack is away from ortho and para, not toward meta
III. Resonance Effects on Benzene
A.
Resonance Donors Activate and ortho, para direct
1) NH2 and OH substituents strongly activate benzene
NH2
NH2
Br
OH
OH
Br
Br
Br2
H2O
Br
Br2
H2O
Br
2)
3)
Reversible Modification of amino and phenol groups can reduce reactivity (later)
Mechanism
NH2
NH2
NH2
E
H
E+
ortho
NH2
Br
NH2
E
H
NH2
E+
meta
E
H
NH2
E
H
NH2
NH2
E
H
E
H
E
H
NH2
NH2
NH2
NH2
NH2
E H
E H
E H
E H
E+
para
4)
B.
Important Points
a) Inductive electron acceptance (N > C electronegativity)
b) Lone pair participates in resonance; overall donating
c) Ortho and para are activated by extra resonance form
d) Polysubstitution is likely because of highly activated ring
Resonance Acceptors Deactivate and Direct Meta
COOH
COOH
COOH
COOH
NO2
HNO3
H2SO4
1%
NO2
19%
80%
NO2
1)
HO
Mechansim
O
HO
O
HO
O
HO
E
H
E+
ortho
HO
O
E
H
O
E
H
E
H
very poor
HO
O
HO
HO
O
O
HO
O
+
E
meta
E
E
H
H
HO
O
HO
O
E
HO
O
H
HO
O
HO
O
+
E
para
E H
2)
E H
E H
E H
Important points:
a) Meta attack prevents (+) from being next to COOH group
b) Meta attack is still destabilized, so the reaction is slow but specific
3)
Halogens are deactivating, but ortho/para directing
Br
Br
Br
Br
Br
Br2
FeBr3
85%
Br
2%
13%
4)
Br
Mechanism
X
X
X
E
H
+
E
ortho
X
X
E
H
E
H
E
H
strong contributor
X
X
X
X
+
E
meta
E
E
H
H
E
H
X
X
X
X
X
E H
E H
E H
E H
+
E
para
strong contributor
5)
C.
Important points
a) Ortho, para attack give a fourth resonance structure
b) Meta attack can’t give a fourth resonance structure
c) All three are slower reactive than benzene
d) Exception to the rule: deactivates, ortho/para directs
Tables 16-1 and 16-2 summarize substituent effects on benzene substitution