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Chemistry 125: Lecture 62March 29, 2010
Electrophilic Aromatic Substitution
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Electrophilic Aromatic
Substitution
Electrophilic Aromatic Substitution
H
HH
H
H
H
D2SO4
H
HH
H
D
H
Sec. 14.4
H
HH
H
H
H
D
A/D via intermediate
+
D2SO4C6D6
etc.
Observable!
Or other electrophiles in place of D+
e.g. NO2+, Br+, HOSO2 , R+, R-C=O R-C=O+HOSO2
+
In electrophilic addition to alkenes, a nucleophile would add in the next step, but here it is easier to lose H+ and recover aromatic stabilization.
H3C CH3
H3C
H3C
CH3
CH3
CH3
+
A
C C
B
D
B
1H vs. 1Hcorrelation in time
H3C CH3
H3C
H3C
CH3
CH3
CH3
+
CH3
CH3
H3C
H3C
CH3
CH3
CH3
+
A
A
C C
B
D
B
C
C
B
D
B
0.3 sec 40°C
CA
DB
Remember
+
+
+
SHMo2 (Simple Hückel Molecular Orbital Program)
Benzene Pentadienyl
Cation addition converts ring to chain.
H
HH
H
H
H
D+
H
HH
H
H
H
D
+
Locus ofodd electron in radical,
+ charge(LUMO)
in cation.
- charge (HOMO)
in anion,SOMO
(nonbonding)
+
+
+
Cf.
Sec. 14.4b
LUMO
X
NO2
++
+ +
HO2N
X
+++
+
H
O2N
X
+
+ +
H
Substituent Effects on Rate (sec. 14.9-14.10)
X
O2N
X
O2N
X X
NO2
+ +NO2
+
(from HONO2/H2SO4)
X Relative Rate (overall)
H [1] Cl 0.03 NO2 6 10-
8
CH3 25 OH 1000
(CH3)3N+ 1 10-
8
donation / withdrawal
(or ) e-donation eases formation of cation intermediates
(or ) e-withdrawal retards formation of cation intermediates
HOH
+
Note: +NO2 is O=C=O with an extra proton in the center
productsintermediates
Cf. Table 14.2
Why is -NO2 e-Withdrawing when -OH is e-Donating?
-NO2 6 10-
8
e-withdrawal retards formation of cation intermediates
-OH 1000 e-donation eases
N
O O
O
HpC
C=C pO-1
0
High HOMO; Good Overlap with Phenyl
Low OMO;Good Overlapwith Phenyl
(but poor E-match)
High HOMO;
Low LUMO;Good Overlapwith Phenyl
OH is a Donor
NO2 is a Acceptor
No Overlap with Phenyl
NO2 isallylic
(willing but not able)
Substituent Effects on Orientation (sec. 14.9-14.10)
X
NO2
+
(from HONO2/H2SO4)
X- Relative Rate (per replaceable H)
H- [1] [1] [1] Cl- 0.0008 0.03 0.13
O2N- 9 10-
8
0.6 10-8 0.03 10-8
H3C- 1 39 46 (CH3)3C- 4 6 72
DirectingActivating
Deactivating
Act
Deact
Deact
(CH3)3N- 3 10-
8
0.6 10-8 + _
ortho meta para
EtOC=O 0.006 0.0006
- 0.003
o/p
m
o/p
“e-donating”
“e-withdrawing”
(steric hindrance)?
X
NO2
++
+ +
HO2N
X
+++
+
H
O2N
X
+
+ +
H intermediates
Activate the ElectrophileHalogenation (sec. 14.4f)
“Cl+”
H
+29 +38
AlCl3 “Lewis acid”catalyst
AlCl5Cl2 vs.
LUMOsSurface Potentials
(Al, like B, has an empty valence AO)AlCl4
leaving group
Activate the Nucleophile
H
OH
C
O
O
OH
H
NH2
100 atm125°C
Self-Igniting Rocket Fuel(1944)
C
OH3C
N
O
O
+
Salicylic AcidKolbe (1860)
OH
CO
OH
H+
Aspirin
loweredHOMO
raisedHOMO
Acetylation of anilinemakes its nitration
controllable.
Taming Aniline Nitration
Friedel-Crafts Alkylation (sec. 14.5)
Friedel-Crafts Acylation (sec. 14.6)
Synthetic Accessibility (sec. 14.7)
End of Lecture 62March 29, 2010
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