12.12 Substituent Effects in Electrophilic Aromatic Substitution: Activating Substituents.
Chemistry of Aromatic Compounds Electrophilic Aromatic Substitution Directing Effects Side-chain...
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Transcript of Chemistry of Aromatic Compounds Electrophilic Aromatic Substitution Directing Effects Side-chain...
Chemistry of Aromatic Compounds
Electrophilic Aromatic Substitution
Directing Effects
Side-chain Reactions
Synthesis
Nucleophilic Aromatic Substitution
Mechanism
CH3 C
CH3
CH3
Cl AlCl3 C
CH3
CH3
CH3
t-butyl carbocation
AlCl4
CH3 C
CH3
CH3
(CH3)3C
H
(CH3)3C (CH3)3C
resonance stabilized intermediate
Cl AlCl3 (CH3)3C
+ HCl(+ AlCl3)
Straight-chain Alkylation can be Accomplished in 2 steps:
Acylation, then Reduction
CH2CH2CH3
CCH2CH3
O
CH3CH2CH2Cl
AlCl3 minor
CH(CH3)2
+
CH3CH2CCl
AlCl3
O
major
H2, Pd/C
2) Oxidation of Alkyl SubstituentsCH3
KMnO4, H2O
COH
O
KMnO4
H2O
CO2H
CH3
CH(CH3)2
KMnO4, H2OCO2H
CO2H
Directing Effects
EDG EWG
electron donating groups electron withdrawing groups activate ring deactivate ring
atom attached isusually sp3
atom attached isusually sp or sp2
meta-Directing Deactivating Groups
CH
O
CH
O
CH
O
CH
O
CH
O
+
+ +
-
ortho and para positions
are deactivated toward
EAS
Comparison
CH3
CF3
Br2, FeBr3
ortho meta para
Brominated product
63 3 34
6 91 3
ortho meta para
rel. rate
25
0.000025
rate rel. to benzene
More Limitations with Friedel Crafts Reactions
Cl
Ring must be at least as activated (reactive) as
NO2 ClCCH3, AlCl3
O
No Reaction
Cl
CH2CH3
+ orthoCH3CH2Cl, TiCl4
Halogens are the AnomolyDeactivators and o,p-Directors
Br
CH3CH2Cl
AlCl3
Br
CH2CH3
CH2CH3
Br
+
rel. rate = 0.5
Inductively withdrawing, hence deactivatingResonance donation causes o,p directing
Reactions of Rings With Two or More Substituents
NO2
OCH3 OCH3
NO2
ClCl2, FeCl3
Activating Group Controls Reaction
Sulfonic Acid Blocks para Position C(CH3)3
Br
H(CH3)3CBr
AlCl3
C(CH3)3
SO3, H2SO4
SO3H
C(CH3)3
Br2, FeBr3
C(CH3)3
SO3H
Br
H3O+
blocks para
CH2CH3
OHBr
1) ClCCH3, AlCl3
O
2) SO3, H2SO4
3) Br2, FeBr3
4) H2 Pd/C5) NaOH, 300 C
o
6) H3O+
O O
SO3H
O
SO3HBr SO3HBr
1)
2) 3) 4)
5,6)
HO2C1)
Cl
AlCl3
2) Cl
O AlCl33) KMnO4, H2O
4) H2, Pd/C
5) NBS, h6) NaOCH3 in CH3OH, heat
(E2 elim of HBr)
1)
O
2)
O
HO2C3)
HO2C
HO2C
Br
4)
5)
6) workup w/ H3O+
“SNA” criteria:
• Strongly deactivated ring
• Leaving group
• Deactivating group(s) ortho &/or para to leaving group (preferably)
• Strong base (nucleophile) such as RO-, NH2-