Post on 31-Dec-2015
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Electrophilic Aromatic Substitution
Activating and Directing effects of substituents already on the ring
Products of Nitration
CH3 CH3
NO2
CH3
NO2
CH3
O2N
+ +HNO3
H2SO4
ortho meta para
63% 3% 34%
CN CN
NO2
CN
NO2
CN
O2N
+ +HNO3
H2SO4
17% 81% 2%
OH OH
NO2
OH
NO2
OH
O2N
+ +HNO3
H2SO4
50% 0% 50%
1 hr
48 hr
0.0003 hr
Mechanism of Electrophilic Aromatic Substitution
E
H
E
H
E
H
E+
E
H
GE
H
GE
H
GE
+G
With a substituent group G
Depending on the nature of the substituent, the substituent G may stabilize the carbocation intermediate and therefore speed the reaction, or it may raise the energy of the carbocation and slow the reaction. Substituents that make the ring react faster (than benzene) with electrophiles are called activators; those that make the ring react slower (than benzene) are called deactivators.
Substituent effects
All activators also direct incoming electrophiles to the ortho- and the para-positions.
Most deactivators direct incoming electrophiles to the meta position. The exceptions are the halogens, which are weakly deactivating yet ortho-para directing.
Classification of Substituents
H
F
Cl
Br
I
Benzene
o,p-directingdeactivators
o,p-directingactivators
Ar
R
NHCOCH3
OR NH2
OH
CHOCO2H
COR
O
CR
O
CN
SO3HNO2
NR3+
m-directingdeactivators
more activatingmore deactivating
Product Distribution in Nitration (Percent %) (Percent %)
X ortho meta para X ortho meta para
(meta-directing Deactivators) (ortho- and para-directing Deactivators)
-N(CH3)3 2 89 11 -F 13 1 86
-NO2 7 91 2 -Cl 35 1 64
-CO2H 22 77 2 -Br 43 1 56
-CN 17 81 2 -I 45 1 54
-CO2CH2CH3 28 72 2 (ortho- and para-directing Activators)
-COCH3 26 72 2 -CH3 63 3 34
-CHO 19 72 9 -OH 50 0 50
-NHCOCH3 19 2 79
o,p-Activators (alkyl & aryl groups)
3º, especially stable
3º, especially stable
p
m
o
E
E
E
CH3
CH3
HE
CH3
H
H
E
CH3
H
HE
CH3
H
E
CH3
HE
CH3
H
H
E
CH3
H
H
E
CH3H
E
CH3
H
H
E
CH3
H
CH3
OH
H
E
OH
H
H
E
OH
H
H
E
OHH
E
OH
HE
OH
HHE HE
OH
HE
OH
H
OH
OH
E
E
EHE
OH
H
E
OH
H
H
E
OH
H
E
OH
H
o,p-Activators with a lp of electrons
4 resonance forms
4 resonance forms
o-
m-
p-
o,p-Deactivators (Halogens)Cl
H
E
ClH
E
ClH
E
ClH
E
H
E
Cl
HE
Cl
H
E
Cl
HE HE
Cl
HE
Cl
Cl
Cl
E
E
EHE
Cl
Cl
Cl
H
E
4 resonance forms
4 resonance forms
o-
m-
p-
meta-directing DeactivatorsCN
H
E
CNH
E
CNH
E
CN
H
E
CN
HE
CN
H
E
CN
HE
CN
HE
H
E
CN
HE
CN
CN
CN
E
E
E
Especially UNSTABLE**
Especially UNSTABLE**
o-
m-
p-
Explanation of meta- deactivators
Meta directors slow the reaction by raising the energy of the carbocation intermediate because they have (in one resonance form, shown below) a positively charged atom attached to the ring. Two positively charged atoms so close together is very high in energy (especially unstable).
NO O
E
H
SO OH
E
H
O
CO CH3
E
H
E
H
N
C
nitro group sulfonic acid ketone nitrile
Summary of Substituent Effects
When the substituent is R (alkyl) or Ar (aryl), the resonance hybrid cation intermediate has three resonance forms. For attack of the electrophile at the ortho or para positions, one of these is a 3º carbocation, which is especially stable. This lowers the energy of the intermediate, thus facilitates (speeds) the substitution reaction at the o- and p- positions.
When the substituent has a lone pair of electrons, such as the halogens, oxygen or nitrogen, the resonance hybrid for attack of the electrophile at the ortho and para positions has four resonance forms. This lowers the energy of the those intermediates, thus facilitates (speeds) the substitution reaction at the o- and p- positions.
Summary of Substituent Effects…
When the substituent has a multiple bond conjugated with the ring, and the second atom from the ring is more electronegative than the first, the substituent deactivates the ring and directs incoming electrophiles meta. It does this by raising the energy of the carbocation intermediates from ortho and para attack by an electrophile even more than it raises the energy of the intermediate resulting from meta attack.
Summary
-H (unsubstituted)
-R or -Ar, ortho- and para- -R or -Ar, meta-
-NH2 or -OH, meta-
-NH2 or -OH, ortho- and para-
-Cl or -Br, ortho- and para-
-Cl or -Br, meta-
-NO2 or -CO2H, meta-
-NO2 or -CO2H, ortho- and para-
Deactivators
Activators
Reactants
[CarbocationIntermediate]
Reaction Progress
Energy
Additivity of substituent effects in disubstituted aromatic rings
Rule 1: If the directing effects of two substituents reinforce each other, the predicted product predominates.
CH3
CO2H
CH3
CO2H
NO2HNO3
H2SO4
(o,p)
(m)
Additivity of substituent effects…
Rule 2: If the directing effects of two substituents oppose each other, the more activating group dominates, but mixtures often result.
NH2
CH3
NH2
CH3
BrBr2
(FeBr3 catnot needed)
(o,p; STRONG activator)
(o,p; weak activator)
Additivity of substituent effects…
Rule 3: Substitution almost never occurs between two substituents meta to each other.
CH3
Cl
CH3
SO3H
Cl
SO3
H2SO4
CH3
Cl
HO3S
CH3
Cl
SO3H
+
but not:
(o,p)
(o,p)
X (too crowded)
Additivity of substituent effects…
Rule 4: With a bulky o,p- director and/or a bulky electrophile, para substitution predominates.
OCCH3
O
SO3H
OCCH3
O
SO3
H2SO4
(o,p; BULKY)
(HSO3+ is a
BULKY electrophile)