Chem 316
Notes-2
H. D. Roth
Resonance and Inductive Effects in Aromatic Compounds
In order to understand the patterns of aromatic substitution it is
imperative to be familiar with the mechanisms by which substituents direct
the incoming substituents. The substitution is governed by resonance effects
and by inductive effects. Let’s begin with resonance effects. We differentiate
between resonance electron-donating and resonance electron-withdrawing
groups in conjugation with an aromatic ring. Typical electron-withdrawing
groups (e.g., NO2, SO3H, CN, COOR, C(=O)R), generate partial positive
charges in the o- and p-positions (note the curved arrows),
N
C
N
+
–
N
–
N
C
C
C
+
–
+
whereas electron-donationg groups (e.g., NR2, OR, F, Cl Br, I) cause
partial negative charges in the o- and p-positions. The mechanism of
delocalization (resonance) leaves the m-positions of either type unaffected.
N(CH3)2
+
–
N(CH3)2
+
+
N(CH3)2
N(CH3)2
–
–
Because the typical aromatic substitution is electrophilic, it follows
that electron-donating groups direct the substitution to the o- and ppositions, because the partial negative charges favor this approach. In
addition, the rates of the o- and p-substitutions are enhanced relative to the
reaction of benzene. These electronic effects are kinetic in nature.
Once the electrophile has been added, we consider the stability of the
resulting carbocation: it is most stable if it is conjugated with the ED group.
This is a thermodynamic effect. Both kinetic and thermodynamic effects
work in the same direction. Only the case of the ortho-substitution is shown
below; you may want to go over the corresponding m- and p-substitution.
1
Chem 316
Notes-2
NH2
H. D. Roth
NH2
Br
Br
Br
H
+ NH2
NH2
H
H
+
Br
+
H
+
In contrast, resonance electron withdrawing groups disfavor the
substitution in the o- and p-positions. Therefore, by default, they direct the
substitution to the m-positions, however at a reduced rate (because of the
nearby partial positive charges).
CN
CN
CN
+
+
Br
Br
Br
+
H
H
H
Once the electrophile has been added (in the m-position), the resulting
carbocation has three resonance contributors; in none of them is the positive
charge conjugated with the EW group. You may want to review the
corresponding substitution in the o- and p-positions. They are unfavorable
because the positive charge conjugated with the EW group.
Inductive effects are strongly distance dependent. Their effect is
strongest in the o-position and falls off toward the m- and p-positions.
D
A
Alkyl groups directly attached to the aromatic ring are inductively
electron-donating (remember hyperconjugation?). All groups containing
electron pairs are inductively electron-withdrawing, including CF3, NR2,
OR, F, Cl, Br, I (in addition to those that are also electron-withdrawing by
resonance, i.e., NO2, SO3H, CN, COOR, C(=O)R).
In addition to directing the regiochemistry of electrophilic aromatic
substitution, the different substituents, particularly the pattern of positive or
negative charges induced by them, also have a profound effect on the NMR
2
Chem 316
Notes-2
H. D. Roth
spectra of aromatic compounds. Recall the drawing below, showing how the
electrons of a nucleus generate different electronic environments for an
adjacent 1H nucleus (or group of nuclei). This effect also applies to the 1H
nucleus itself. Because the bonding electrons induce a field, that at the
nucleus opposes the external field, they shield the 1H nucleus.
On the other hand, a 1H nucleus without an electron (a proton, H+)
does not experience an induced magnetic field: H+ is NOT shielded. The
chemical shift for a carboxylic acid 1H nucleus is “strongly deshielded”, to
10 – 12 ppm. From this observation we can deriive that a positive charge at
or near the nucleus deshields whereas a negative charge shields.
We begin by looking at the effects of electron-donating or
withdrawing groups in conjugation with a double bond; these effects can be
explained or predicted by delocalization or resonance considerations.
For example, oxacyclohexene is resonance-stabilized by electron
donation, creating a negative charge on the β alkene carbon, thereby
shielding the attached 1H nucleus (4.65 ppm). In contrast, cyclohexenone is
resonance-stabilized by the electron withdrawing carbonyl function. The
positive charge created on the β alkene carbon deshields the attached 1H
3
Chem 316
Notes-2
H. D. Roth
nucleus (6.88 ppm). These considerations allow us to rationalize and assign
the divergent chemical shifts of these compounds.
O
O
H
O
O
H
H
H
4.65 ppm
6.37 ppm
5.93 ppm
6.88 ppm
We can also check the chemical shifts of cycloheptatrienyl cation (9.2
ppm) and cyclopentadienyl anion (5.5 ppm).
Applying this concept to the electron-donating or withdrawing groups
in conjugation with an aromatic ring, we conclude that typical electronwithdrawing groups (e.g., NO2, CN), cause incrementally deshielded NMR
shifts in the o- and p-position,
N
C
N
+
–
N
–
N
C
C
C
+
–
+
whereas electron-donating groups (e.g., NR2, OR) cause incremental
shielding effects in the o- and p-position. The mechanism of delocalization
(resonance) leaves the m-positions of either type unaffected.
N(CH3)2
+
–
N(CH3)2
–
+
+
N(CH3)2
N(CH3)2
–
Now consider an aromatic compound with a resonance electronwithdrawing group, i.e., nitrobenzene. The spectrum has three signals at
~6.5, 6.7, and 7.1 ppm. Please note that all resonances are upfield, less
deshielded than benzene (7.23 ppm). How do we assign these resonances?
4
Chem 316
Notes-2
H. D. Roth
Ho
NO2
Hm
Ho
Hp
Hm
Please note that there are two o- and two m-nuclei, and one p-nucleus.
The o-nuclei have only one nearest neighbor whereas the m- and p-nuclei
each have two nearest neighbors. Thus, the signal appearing as a doublet
must represent the o-Hs, the signals appearing as triplets must be the m-, and
p-nuclei. One of these is obviously weaker than the other: the signal at 6.7
ppm must represent the p-nucleus.
Given this assignment, we note that the o- and p-1H nuclei are
significantly shielded and even the m-1H nuclei are slightly shielded relative
to the benzene 1H nuclei (7.25 ppm). We ascribe these chemical shifts to the
partial negative charges (causing shielding) in the o- and p-positions.
The spectrum of N,N-dimethylaniline, an aromatic compound bearing
a resonance electron-donating substutuent, is significantly different.
5
Chem 316
Notes-2
H. D. Roth
Ho
N(CH3)2
Hm
Ho
Hp
Hm
Again, the spectrum has three signals, at ~7.5, 7.7, and 8.2 ppm; all
resonances are downfield, more deshielded, than that of benzene (7.23 ppm).
We assign these resonances on similar considerations as above. The doublet
(8.2 ppm) must represent the o-Hs, the triplets the m-, and p-nuclei. The
weaker triplet (7.7 ppm) must represent the p-nucleus. The o-1H nuclei are
significantly deshielded whereas the p- nucleus and even the m-1H nuclei
are slightly deshielded. We ascribe these chemical shifts to the partial
positive charges (causing deshielding) in the o- and p-positions. The
significantly greater effect on the o-nuclei must be an inductive effect.
6