OWLS: Electrophilic Aromatic Substitution Solutions - UCLA

OWLS: Electrophilic Aromatic Substitution Solutions
1. Protonate/deprotonate: Found in many mechanisms.
OH H OSO 3H OH 2 + OSO 3H
Displacement of a leaving group by a nucleophile: Found in S N2.
OH 2
Cl
Cl + H 2O
Ionization of a carbon-leaving group bond: Found in S N1, E1.
OH 2
+ H 2O
Carbocation accepts a nucleophile: Found in S N1, some alkene and alkyne addition
reactions.
OH 2
“Carbocation accepts a nucleophile” is not the same thing as S N1. The S N1
mechanism includes “carbocation accepts a nucleophile” but not all “carbocation
accepts a nucleophile” mechanism steps are in S N1 mechanisms. For example,
“carbocation accepts a nucleophile” is also part of the mechanism for many
electrophilic additions to carbon-carbon pi bonds.
Deprotonate carbocation to form pi bond: Found in E1, EAS.
H OH 2
+ H 3O
“Deprotonate carbocation” is not the same thing as E1. The E1 mechanism includes
“deprotonate carbocation” but not all “deprotonate carbocation” mechanism steps are
in E1 mechanisms. For example, “deprotonate carbocation” is also part of the EAS
mechanism.
Carbocation rearrangement: Found in many carbocation reactions.
H
OH 2

β-Elimination: Found in E2.
H OCH 3
I
+ HOCH 3 + I
Electrophilic addition to pi bond: Found in some carbon-carbon pi bond addition
reactions and EAS.
H OH 2
+ H 2O
Resonance: Not really a mechanism step because the resonance contributors have no
lifetime (only the resonance hybrid really exists). Included because it is common in
reaction mechanisms.
2. (a) Cl Cl AlCl 3 Cl Cl AlCl 3
O
O CH 3
Cl Cl AlCl 3
O
O CH 3
Cl H Cl AlCl 3
O
O CH 3
Cl H
O CH 3
Cl
O
O CH 3
Cl H
OWLS: Electrophilic Aromatic Substitution Solutions 2
O
O
O CH 3
Cl H
O
O CH 3
Cl H
The ester group is large enough to cause the para isomer to be formed in greater
amount than the ortho isomer.
(b) To determine which reaction is faster, compare the rate-determining steps of the
two reactions. For any EAS mechanism, the rds is the step in which the aromatic

3. (a)
ring is attacked by the electrophile and aromaticity is lost. In this case, the only
difference between the reactants is the presence of a hydroxyl (OH, which makes
this molecule a phenol) or an ester group. How does this effect the rds? Recall
that a more stable carbocation is formed more quickly. How do the hydroxyl and
ester groups affect the carbocation stability? Both arenium ions have four
significant resonance contributors, but the ester oxygen lone pairs are not as
readily available to stabilize the carbocation as the hydroxyl oxygen lone pairs
because the ester oxygen lone pairs are delocalized by resonance with the ester
carbonyl.
Lone pair delocalized
by C=O resonance
O
O CH 3
Cl H
O
O CH 3
Cl H
Lone pair not delocalized
by C=O resonance
OWLS: Electrophilic Aromatic Substitution Solutions 3
O
Cl H
Arenium ion from ester Arenium ion from phenol
The arenium ion of reaction (i) is more stable, and thus reaction (i) is faster.
(c) A wide variety of changes can be made. Extending the idea from part (b), any
structural change that further reduces the availability of the ester oxygen lone
pairs will decrease the stability of the arenium ion and hence decrease the reaction
rate. Replacement of the ester methyl group (weak electron donating group) with
a trifluoromethyl group (powerful electron withdrawing group) decreases the
availability of the ester oxygen lone pairs due to an inductive effect.
(b)
Br 2, Fe
or Br 2, FeBr 3
CH 3
Cl 2
AlCl 3
O
O CF 3
Br
Cl 2
AlCl 3
CH 3
Cl
O
O CF 3
Cl
H

4.
(c)
(d)
(e)
(f)
(g)
H 3C
OCH 3
H OSO 3H
or
O
NH 2
Cl
CH 3
SO 3
H 2SO 4
Cl
AlCl 3
NO 2
benzene
aq. HONO 2
aq. H 2SO 4
HO 3S
AlCl 3
1. NaNO 2, aq. HCl
2. PhOH
H 3C
H 3C
OWLS: Electrophilic Aromatic Substitution Solutions 4
CH 3O
O 2N
O
N
NO 2
Consider arenium ion
stability plus steric effects.
N
OH
H OSO 3H
5. In each case, electrophilic attack on the aromatic ring gives the more stable arenium
ion. Draw all of the resonance contributors if necessary to convince yourself.
(a)
aq. HONO 2
aq. H 2SO 4
NO 2

(b)
(c)
OCH 3
SO 3
H 2SO 4
OWLS: Electrophilic Aromatic Substitution Solutions 5
OCH 3
The major product choice is based on the assumption that a benzene ring
offers more steric hindrance than a methoxy group.
O
+
CH 3
O
Cl
AlCl 3
6. Remember that Ph = phenyl = C 6H 5 = monosubstituted benzene ring.
7.
O N O H OH 2 O N OH
H OH 2
Ph NH2 N O Ph N N O
Ph N
Ph N N OH
Ph N N OH
H OH 2
NH 2
CH 3
excess Br 2
H
NH 2
Br Br
CH 3
O
O
CH 3
SO 3H
H OH 2 O N OH2 O N + OH 2
H OH 2
H
N O
H OH 2
Ph
N
H
N OH
Ph N N OH2 Ph N N
Ph N N
excess CH 3I
K 2CO 3
N(CH 3) 3 Br
Br Br
The NH 2 and CH 3 (electron-donating) substituents of 4-methylaniline give its benzene
ring enough nucleophilicity so that it can react with Br 2 in the absence of a Lewis acid
catalyst such as FeBr 3. The reactivity is also enhanced by the increased stability
imparted to the arenium ion by the NH 2 and CH 3 groups.
Potassium carbonate is a weak base that is necessary to convert all of the amine to the
ammonium salt. (Work out the mechanism to see how this happens.) Other weak
bases could also be used.
Bromination must be conducted before alkylation because the R 3N + substituent is a
meta directing group. When there are multiple directing groups on the benzene ring,
the strongest electron donor dominates. (In this case a methyl group is a stronger
electron donor than an ammonium group, which is not an electron donor at all! For
more on this concept ask Dr H for the EAS Supplemental Reading.)
CH 3

NH 2
CH 3
excess CH 3I
K 2CO 3
N(CH 3) 3 Br
CH 3
excess Br 2
FeBr 3
N(CH 3) 3 Br
Br Br
OWLS: Electrophilic Aromatic Substitution Solutions 6
CH 3