Influence of substituents on the through-space shielding of aromatic rings

Article abstract of DOI:10.1021/jo202203r

A series of naphthalene derivatives, bearing a methyl group and a substituted phenyl ring in a 1,8-relationship, have been synthesized. The chemical shifts of the protons of the methyl group, which are pointed toward the shielding zone of the phenyl ring,

Full text of DOI:10.1021/jo202203r

Article
pubs.acs.org/joc
Influence of Substituents on the Through-Space Shielding
of Aromatic Rings
Colin W. Anson† and Dasan M. Thamattoor*
Department of Chemistry, Colby College, Waterville, Maine 04901, United States
S
* Supporting Information
ABSTRACT: A series of naphthalene derivatives, bearing a methyl group and a substituted phenyl
ring in a 1,8-relationship, have been synthesized. The chemical shifts of the protons of the methyl
group, which are pointed toward the shielding zone of the phenyl ring, were monitored as the phenyl
substituents were varied. This work indicates that the shielding effect of the phenyl ring is not so
severely altered by the substituents as to significantly influence the chemical shift of the methyl group.
Nonetheless, within the small changes observed experimentally, there appears to be a tendency for
electron-withdrawing X to shift the methyl signal downfield, whereas electron-donating X-groups cause
a more upfield shift. Polarization and field effects are discussed as possible causes for this phenomenon.
Chemical shifts computed for selected members of the series, using the recently published procedures
of Rablen and Bally, are in agreement with the experimentally observed trends.
INTRODUCTION
■
In the 1930s, well before the advent of NMR spectroscopy,
Pauling,1 Lonsdale,2 and London3 provided a ring current model
to describe the diamagnetic anisotropy of benzene. Some 20 years
later, Pople developed a magnetic dipole description of that model
1
to explain the abnormal H NMR chemical shift of benzene and
other aromatic molecules.4 Since then, a variety of computational
Figure 1. The chemical shifts (in δ ppm) of nitrobenzene and aniline ring
protons. The difference from the shift of benzene protons (δ 7.34 ppm)
are noted in parentheses. All shifts were measured in CDCl3.10
methods have been employed to analyze the relationships among
ring currents, aromaticity, and NMR chemical shifts.5 The gist of
these analyses, in a general sense, is that the circulation of
π-electrons in aromatic rings, induced by an external magnetic field,
deshields the outer protons, whereas the inner protons, or those
located above/below the plane of the rings, are shielded. The ring
current model for benzene has been vigorously challenged6 and
defended.7 It has been also pointed out that the magnetic
susceptibilities and shielding induced by the circulating π-electrons
have a much larger component normal to the plane of the ring, and
local effects, rather than the ring current, are more important
determinants of the chemical shifts of peripheral protons.8 Indeed,
the chemical shifts of phenyl protons are dramatically influenced by
the presence of substituents due to various local factors such as
inductive, field, and resonance effects.9 This can be seen, for
example, in the large differences in chemical shifts of the ring
protons in nitrobenzene (1) and aniline (2) compared to benzene
(Figure 1).10 In the electron deficient aromatic ring of 1, the proton
signals are more downfield, and just the opposite is true for the
electron-rich ring in 2. The effects are particularly amplified at the
ortho/para positions, and resonance contributions to electron
densities have been invoked to explain these observations.9a
aromatic rings by substituents, and the consequent effects on
the shielding surface.11 Using methane held at various positions
above the plane of the phenyl ring in 1 and 2 (Figure 2),
Figure 2. Martin’s model for computing through-space shielding
effects of the aryl ring in 1 and 2.11
Martin’s group calculated the through-space shielding influence
of the phenyl ring in these compounds and developed an
algorithm to predict shielding above substituted aromatic rings.
Their calculations suggest that “the perturbation due to the
presence of a substituent has a relatively minor effect on the
shielding surface and that the major effect is due to the
aromatic ring.” This result is in sharp contrast to the dramatic
effect that these substituents have on the (de)shielding of the
ring protons (vide supra).
But how do phenyl substituents affect the chemical shifts of
protons in the shielding zone of the ring? Unfortunately,
research literature addressing this question is surprisingly scant.
To the best of our knowledge, there is just one computa-
tional report, that of Martin and co-workers, that specifically
investigated the perturbation of diamagnetic anisotropy of
Received: October 25, 2011
Published: January 18, 2012
© 2012 American Chemical Society
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The literature on experimental work to test the through-
space shielding effects of substituted phenyl rings is also limited
to a solitary report, that of Penn and Mallory, in 1975.12 Using
a low field NMR spectrometer operating at 60 MHz and 3 as
their model system, these workers attempted to find a
correlation between the out-of-plane shielding of the phenyl
ring and its substituent X. In this study, however, X was
confined to just three substituents (besides hydrogen), with
a narrow range of electronic properties. Common electron-
withdrawing groups such as nitro, carbonyl, and cyano groups
were conspicuously absent. Nonetheless, within this limited
range of variously substituted 3, they noted that the chemical
shifts of the methyl group projected toward the shielding zone
of phenyl ring were ever so slightly upfield when X = OCH3,
Cl, and CH3 compared to when X = H, but the variations
among these chemical shifts were quite small. After considering
several factors that could potentially influence shielding, such as
substituent effects on ring currents and electric field effects of
substituent polarities, Penn and Mallory concluded that “we do
not think any sound inferences can be drawn from our data
regarding the extent to which substituents influence ring
currents.” While acknowledging that they could not provide a
“fully satisfactory explanation” of their results, they offered the
tentative suggestion that perhaps the anisotropy of the local
magnetic susceptibilities of the substituents played an important
role in determining shielding. They do note, however, that
there is no conclusive evidence supporting such a hypothesis in
their data.
Scheme 1. Syntheses of Naphthalene Derivatives 4a−j
In the first step, commercially available (8-bromonaphthalen-1-yl)
methanol (5) was reduced to 1-bromo-8-methylnaphthalene (6)
following the procedure of Kesharwani and Larock.13 Subsequently,
4a−i were prepared by the palladium catalyzed Suzuki−Miyaura
coupling of 6 with the appropriate aryl boronic acids.14 Catalytic
reduction of 4b (X = NO2) afforded 4j (X = NH2), the tenth
member of the series.
X-ray Crystallographic Studies. To obtain more structural
information about our system, particularly the relative disposition
of the methyl group and the substituted phenyl ring, we carried
out single crystal X-ray diffraction experiments. We were able to
grow suitable crystals for 7 of our 10 derivatives, namely, 4b−e
and 4g−i, and solve their structures. These structures are shown in
Figure 3, and selected data are summarized in Table 1. In each
case, the crystal structure indicated that the phenyl ring was
roughly orthogonal to the naphthyl ring but somewhat splayed
away from the methyl group that is across from it. Two of the
protons on the methyl group were oriented toward the shielding
zone of the phenyl ring in the solid state. The distances of these
protons from the centroid of the phenyl ring are collected in Table 1.
Furthermore, the bond connecting the phenyl and naphthyl
rings is the length of a normal single bond between two sp2-
hybridized carbon atoms, indicating no conjugation between the
two ring systems. These bond lengths, for example, are comparable
to 1,8-diarylnaphthalenes where rotation of the phenyl ring is
severely restricted.15 Thus, it appears unlikely that the electronic
effects of the substituents on the phenyl ring are mesomerically
transmitted into the naphthyl ring and influence the chemical shift
of the methyl signal by altering local contributions.
In this report, we describe a comprehensive study that builds
on and extends the work of Penn and Mallory. We have
prepared a series of 10 naphthalene derivatives (4a−j), related
to 3, bearing a methyl group and a substituted phenyl ring
in 1,8-relationship. This study includes a wide variety of sub-
stituents ranging from powerful electron-withdrawing groups to
strong electron donors. The chemical shifts of the protons of
the methyl group on the naphthalene ring, which are pointed
toward the shielding zone of the phenyl ring, were monitored
as the substituent X was varied.
1H NMR Spectroscopy. All 1H NMR spectra were
recorded in deuterated chloroform at 500 MHz. The methyl
signal of 1-methylnaphthalene appears at δ 2.685 ppm, and the
installation of a phenyl ring at the 8-position, as in 4a, causes an
upfield shift of the 1-methyl protons to δ 2.009 ppm (Table 2).
Thus, it is clear that the phenyl ring exerts a substantial
shielding influence, to the extent of δ 0.676 ppm (or 338 Hz),
on the chemical shift of the methyl protons across from it.
Table 2 also includes the chemical shifts of the methyl group on
the naphthalene ring for the other derivatives employed in this
study. Columns three and four in Table 2 show the difference
in this chemical shift between each of the derivatives 4b−j and
4a and the ratio of this difference to the shielding exerted by
the phenyl ring in 4a (i.e., 338 Hz), respectively. Thus, these
last two columns provide a measure of how the various
substituents X affect the shielding exerted by the phenyl ring.
RESULTS AND DISCUSSION
■
Syntheses of 4a−j. The syntheses of compounds 4a−j were
accomplished according to the reactions shown in Scheme 1.
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Figure 3. Single-crystal X-ray structures of 4b−e (top) and 4g−i (bottom).
As can be seen from Table 2, the substitution of X, spanning
a broad range of electronic properties, into the phenyl ring in
4a, has but a very small effect on the chemical shift of the
methyl group on the naphthalene ring. Of all the para sub-
stituents, the powerful electron-donating amino group
exerts the strongest influence by inducing an 11% shift in the
methyl signal toward the downfield direction as compared to
the phenyl group itself (4j vs 4a). A similar downfield shift,
albeit to a much smaller extent, is also observed for analogues
containing other electron donors in the para position such as
the methoxy (4i) and methyl (4h) groups. Although smaller,
electron-withdrawing groups seem to have just the opposite
effect on the chemical shift of the methyl signal, which is shifted
ever so slightly more upfield; the p-cyano derivative (4d)
induces the largest change followed by the p-nitro (4b) and
p-formyl (4c) analogues. The effect of halogens on the chemical
shifts is also interesting. Fluorine is an effective π donor but, by
virtue of its high electronegativity, has a strong electron-
withdrawing inductive effect. According to our data, placing
fluorine in the para position, as in 4e, induces a slight upfield
shift in the methyl signal that is similar to that of the p-nitro
derivative (4b). Switching fluorine to the ortho position (4f),
however, moves the methyl chemical shift in the opposite
(downfield) direction by an order of magnitude. The p-chloro
analogue (4g) also induces a more downfield chemical shift of
the methyl signal relative to that displayed by the parent
compound 4a.
Computational Results. Are the extremely small changes
observed in the chemical shift of the naphthyl methyl signal
with varying substituents on the phenyl ring truly significant, or
are they simply consequences of minor structural variations in
the relative disposition of the methyl group and substituted
phenyl ring in our series of compounds? While this question
remains difficult to answer, the observed trends are nonetheless
intriguing. It has been noted previously that a Hammett-type
correlation, associating the chemical shifts of in-plane protons
and substituents on the phenyl ring, could not be establish-
ed.9c,16 Such a correlation also does not appear to exist for the
through-space shielding effects noted in our system (4a−j).
One possible clue for the observed trend perhaps comes from
the computational work of Martin’s group, which modeled the
through-space shielding effect of benzene−cation complexes on
diatomic hydrogen (Figure 4).17 Martin and co-workers noted
that complexation of the cation with one face of the benzene
ring diminished the electron density on the opposite face of
the ring, which is closer to H2, resulting in a shielding of the
proximal hydrogen. According to them, “...the magnitude of the
shielding effect entirely due to complexation is substantial...”
and “...the decreased π electron density on the side of the
complexed benzene ring opposite the cation polarizes the
covalent bond of diatomic hydrogen, increasing the electron
density near the proximal hydrogen, with the consequence that
the proximal hydrogen becomes more shielded.”17 By analogy,
it is conceivable that the electron density of the phenyl ring in
our system is also perturbed in a similar fashion. Thus, as
shown in Figure 5, one could envision an electron-withdrawing
group diminishing the electron density of the phenyl ring
and polarizing the C−H bonds of the naphthyl methyl ever
so slightly that the hydrogens are now somewhat shielded
(Figure 5a). An electron-donating group, on the other hand,
would have just the opposite effect (Figure 5b). We do not,
however, have a good explanation for the trend observed for the
two para-substituted halogens. They could possibly represent a
trade-off between their electron-withdrawing inductive effects
and electron-donating mesomeric effects, with other, as yet
unidentified, factors mixed in. Field effects (vide infra) could
also play a role. In any event, the overall influence on the
change in chemical shift of the probe methyl group caused by
the substituents on the phenyl ring is quite small in most of the
derivatives that we examined.
In recently published work, Rablen and Bally have described
quantum chemical procedures for accurately computing chem-
ical shifts of protons in organic molecules.18 Although the
range of values for the methyl signal in our series, 4a−j, is
extremely narrow, we decided to apply these new computa-
tional techniques18 to three exemplars in the series, namely 4a,
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1
Table 2. Experimentally Obtained H NMR Chemical Shift
Data, in CDCl3, for the Methyl Signal in 1-
a
Methylnaphthalene and 4a−j
Δ(δCH3 for each
Δ(δCH3 for each
compound − δCH3 compound − δCH3
δCH3
ppm
for 4a), in ppm
for 4a) in Hz/338
b
c
compound
(Hz)
Hz
1-methylnaphthalene 2.685
0.676 (338)
0 (0)
1
4a (X = H)
2.009
2.001
2.006
1.990
2.002
2.084
2.026
2.030
2.037
2.085
0
4b (X = p-NO2)
4c (X = p-CHO)
4d (X = p-CN)
4e (X = p-F)
4f (X = o-F)
−0.008 (−4)
−0.003 (−1.5)
−0.019 (−9.5)
−0.007 (−3.5)
0.075 (37.5)
0.017 (8.5)
0.021 (10.5)
0.028 (14)
−0.012
−0.004
−0.028
−0.010
0.111
0.025
0.031
0.041
4g (X = p-Cl)
d
4h (X = p-CH3)
4i (X = p-OCH3)
4j (X = p-NH2)
0.076 (38)
0.112
a
b
The shift of TMS (δ 0.000 ppm) is used as reference. This is
the difference between each value in column 2 and the δCH3 for 4a
c
(2.009 ppm). This is ratio of each value in column 3 (in Hz) to
d
338 Hz. The reported data is for the methyl group on the naphthalene
ring.
Figure 4. Polarization of diatomic hydrogen by a cation-π complex.17
This leads to a greater shielding of the hydrogen proximal to the ring.
Figure 5. Polarization of the methyl C−H bonds when an electron-
withdrawing group (EWG) is present on the phenyl ring (a) as
opposed to an electron-donating group (b).
4d, and 4j. Compound 4a (X = H) was chosen to serve as the
standard, whereas 4d (X = CN) and 4j (X = NH2) represented
analogues with a strong electron-withdrawing and -donating
group, respectively. Furthermore, according to our experimen-
tal observations, both 4d and 4j displayed the largest difference,
in opposite directions, on the chemical shift of the methyl
group, as compared to 4a.
The calculations were performed in two different ways. In
one approach, structures of 4a, 4d, and 4j were optimized first
at the B3LYP/6-31G* level of theory (Figure 6), and
subsequently, the chemical shift of the methyl group was
computed, in chloroform, on the optimized structures using
GIAO/WP04/6-31G(d) and GIAO/WP04/cc-pVDZ proce-
dures.18 In each case, the shifts for the three hydrogens in the
methyl group were averaged and then scaled according to the
recommended protocol.18
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hydrogen shifts (three for each orientation of the methyl
group) for each set were computed, averaged, and scaled as
before.19 These calculations also included chloroform as solvent,
and the results are displayed in Table 3.
1
Table 3. Computed H NMR Chemical Shift Data, in
Chloroform, for the Methyl Signal in Optimized and
Constrained Versions of 4a, 4d, and 4j
CH3 shift in δ ppm
GIAO/WP04/6-31G*
CH3 shift in δ ppm
GIAO/WP04/cc-pVDZ
compound
Figure 6. The B3LYP/6-31G* optimized structures of 4a (left), 4d
(center), and 4j (right).
4a optimized
4d optimized
4j optimized
1.968
1.954
2.078
1.345
2.050
2.031
2.152
1.528
In a second approach, benzene, benzonitrile, and aniline were
optimized (B3LYP/6-31G*), and the naphthalene ring was
then appended to each to generate “constrained” versions of 4a,
4d, and 4j, with Cs symmetry, in which the two aryl rings were
orthogonal to each other. Subsequently, the α and β angles
were set to 124.339° and 124.997°, respectively, to splay
the phenyl ring and the methyl group away from each other
(Figure 7). These values represent the average of the
4a(Me1)/4a(Me2)
(constrained)
4d(Me1)/4d(Me2)
(constrained)
1.291
1.540
1.471
1.724
4jpyr1(Me1)/
4jpyr1(Me2)
(constrained)
4jpyr2(Me1)/
4jpyr2(Me2)
(constrained)
1.455
1.730
As can be seen from Table 3, the computed methyl signals in
the optimized structures of 4a, 4d, and 4j more closely
reproduce the experimental values and follow a trend that is
consistent with that observed experimentally; i.e., the methyl
group in the cyano derivative, 4d, has a slightly more upfield
shift than the one in the parent compound 4a. By contrast, the
methyl signal in the amino derivative, 4j, is more downfield
than the corresponding signal in 4a. Furthermore, the amino
group has a larger effect than the cyano substituent, just as
observed in the experimental values. When the geometries of
these compounds are artificially constrained so as to erase
conformational differences among them with respect to the
relative orientations of the phenyl ring and methyl group, all of the
calculated values move further upfield. Even so, the computed and
experimental methyl shifts display the same trend.
Figure 7. The α and β angles, averaged from the B3LYP-/6-31G*
optimized structures of 4a, 4d, and 4j, worked out to 124.339° and
124.997°, respectively. These values were used to constrain the Cs
structures shown in Figure 8.
corresponding angles in the optimized structures of 4a, 4d,
and 4j described above. Finally, the methyl group was oriented
in two different ways, noted in parentheses as Me1 and Me2 for
the structures shown in Figure 8. Note that 4jpyr1 and 4jpyr2
Another interesting experimental observation is the rather
substantial change in the opposite direction (relative to 4a) in
going from 4e, which has the fluorine para to the naphthyl ring,
to 4f, in which the fluorine is ortho. This suggests that another
effect far more important than just electron density variations
within the phenyl ring might be at play. Wheeler and Houk
reported recently that, contrary to popular belief, electrostatic
potentials above the centers of substituted benzenes are due
primarily to through-space effects of substituents rather than
the π polarization of the aryl ring.20 Although counterintuitive,
it has been calculated that local changes in electron density
(“π-electron-rich” vs “π-electron-poor” aryl rings) are minor
players in determining molecular electrostatic potentials, and
field effects of the substituents are far more important.21 It is
conceivable that an analogous situation perhaps exists for
magnetic properties as well. In the optimized structure of 4e
(B3LYP/6-31G*), the methyl group (using its carbon as the
reference point) is 5.589 Å from the fluorine, which compares
well with the distance of 5.506 Å determined experimentally
from the X-ray structure. In the calculated structure of 4f,
however, that distance drops to 3.306 Å (Figure 9). As field
effects are a function of distance, the greater proximity of the
highly electronegative fluorine to the methyl group in 4f
compared to 4e could account for the more pronounced effect
on the methyl shift in the former.
Figure 8. Constrained structures of 4a, 4d, and 4j for 1H NMR
chemical shift calculations.
(Figure 8) represent conformations in which the amino group
is pyramidalized in opposite directions. Thus, a total of six
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observed for the signal of the naphthyl methyl in 4a−j, it
appears that electron-withdrawing groups have a slightly shield-
ing effect, whereas electron donors are somewhat deshielding.
These small effects are rationalized in terms of through-space
polarization of the C−H bonds of the methyl group by the
phenyl ring. Field effects, which are dependent on the
proximity of the substituent to the methyl group, appear to
be especially important as exemplified by the fluoro derivatives
4e and 4f. Chemical shift calculations on optimized structures
of selected molecules in the series are consistent with the
experimental observations. Even when these molecules were
constrained to remove conformational differences among them
with respect to the relative orientations of the phenyl ring and
methyl group, the trends in the computed chemical shifts
parallel those found experimentally.
Figure 9. The B3LYP/6-31G* optimized structures of 4e (left) and 4f
(right). The distance between the carbon of the methyl group and
fluorine is noted in each structure.
EXPERIMENTAL METHODS
■
General Experimental Procedures. All solvents and reagents
were used as obtained from commercial sources. Unless otherwise
noted, all reactions were carried out under an argon atmosphere in
oven-dried glassware. The synthesis of 1-bromo-8-methylnaphthalene
(6) was carried out following literature procedures.13 Microwave
reactions were carried out in a scientific reactor equipped with a single
magnetron capable of up to 1200 W of power output. Flash chromato-
graphy was performed on prepacked silica gel columns (70−230
mesh). NMR spectra were recorded at 500 MHz for 1H and 125 MHz
for 13C in CDCl3. The shifts are reported in δ ppm and referenced to
These experimental findings are supported by chemical shift
calculations, which were performed using the procedures
described above, in chloroform as solvent, on the optimized
structures of 4e and 4f. Using the average values of α =
124.393° and β = 125.394°, obtained from the optimized
structures of 4e and 4f, constrained structures were built
following the previously discussed method and are schemati-
cally shown in Figure 10. Calculations on these structures,
1
either tetramethylsilane (TMS) (for H NMR spectra) or the central
peak of the carbon triplet signal of CDCl3 (for 13C NMR spectra).
FTIR spectra were acquired with an attenuated total reflectance (ATR)
accessory for solids, and in the neat form, with sodium chloride plates, for
liquids. GC−MS data were obtained with a capillary gas chromatograph
interfaced with a quadrupole, triple-axis mass selective detector operating
in the electron impact (EI) mode. High resolution mass spectra were
obtained on a direct analysis in real time−time-of-flight (DART-TOF)
mass spectrometer. Melting points are uncorrected.
General Procedure for the Suzuki−Miyaura Coupling of 6
with Aryl Boronic Acids.14 Preparation of Compounds 4a−i. To
a mixture of the appropriate arylboronic acid (1.5 mmol), 6 (1 mmol),
cesium carbonate (1 mmol), and anhydrous DMF (10 mL), degassed
with nitrogen or argon, was added tetrakis(triphenylphosphine)-
palladium(0) (0.05 mmol). The mixture was stirred magnetically and
heated by microwave irradiation at 140 °C for 45 min, allowed to cool to
room temperature, and reheated at 140 °C for another 45 min. The
reaction mixture was then cooled to room temperature again, diluted with
ethyl acetate and water, and filtered through a pad of Celite under
vacuum. The organic and aqueous layers were separated, and the latter
was extracted with additional ethyl acetate. The organic layers were
combined, washed with water and brine, dried over anhydrous MgSO4,
gravity filtered, and freed of solvent. The crude material was absorbed
onto silica gel and purified using flash chromatography (either hexanes or
5% ethyl acetate in hexanes). Yields and characterization data for each
compound are reported below.
1
Figure 10. Constrained structures of 4a, 4d, and 4j for H NMR
chemical shift calculations.
with chloroform as solvent, led to somewhat more upfield
chemical shifts, but the experimentally observed trend was
also reproduced by the computed values. The data are collected
in Table 4.
1
Table 4. Computed H NMR Chemical Shift Data, in
Chloroform, for the Methyl Signal in Optimized and
Constrained Versions of 4e and 4f
CH3 shift in δ ppm
GIAO/WP04/6-31G(d)
CH3 shift in δ ppm
GIAO/WP04/cc-pVDZ
compound
4e optimized
4f optimized
1.985
2.151
1.362
2.050
2.207
1.531
1-Methyl-8-phenylnaphthalene (4a).22 Clear, colorless, viscous
1
liquid: yield 17%; H NMR δ 7.85 (dd, J = 8.2, 1.4 Hz, 1H), 7.77 (d,
4e(Me1)/4e(Me2)
(constrained)
J = 8.1 Hz, 1H), 7.43 (dd, J = 8.1, 7.0 Hz, 1H), 7.39−7.32 (m, 6H),
7.30 (dd, J = 7.0, 1.4 Hz, 1H), 7.22 (d, J = 7.0 Hz, 1H), 2.01 (s, 3H);
13C NMR δ 145.3, 140.6, 135.6, 135.2, 131.2, 129.9, 129.8, 129.7,
129.0, 127.7, 127.6, 126.9, 125.7, 124.5, 25.3; FTIR (neat) v 3055,
1582, 1492, 1444, 1030, 1039, 820, 773, 703 cm−1; LRMS (EI) m/z
218 (M+), 203, 189, 101.
4f(Me1)/4f(Me2)
(constrained)
1.424
1.578
Conclusions. In our particular system, namely compounds
4a−j, it is clear that the substituents on the phenyl ring have
very little influence on the chemical shift of the methyl protons
that are in its (phenyl ring’s) shielding zone. This is in sharp
contrast to the profound effect that phenyl substituents are
known to have on the chemical shifts of protons that are on the
periphery of the ring. Within the small effects that were
1-Methyl-8-(4-nitrophenyl)naphthalene (4b). Bright yellow,
1
crystalline solid: yield 62%; mp 157−160 °C; H NMR δ 8.27 (d, J =
8.4 Hz, 2H), 7.91 (dd, J = 8.2, 1.3 Hz, 1H), 7.81 (d, J = 8.1 Hz, 1H),
7.52 (d, J = 8.4 Hz, 2H), 7.47 (dd, J = 8.1, 7.1 Hz, 1H), 7.44−7.40 (m,
1H), 7.30−7.25 (m, 2H), 2.00 (s, 3H); 13C NMR δ 152.3, 147.1,
138.1, 135.2, 134.6, 130.60, 130.55, 130.5, 130.2, 129.6, 127.8, 126.2,
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124.4, 123.1, 25.7; FTIR (ATR) v 2985, 1594, 1515, 1345, 1276, 1260,
851, 822, 751 cm−1; LRMS (EI) m/z 263 (M+), 215, 202, 189.
4-(8-Methylnaphthalen-1-yl)benzaldehyde (4c). Pale yellow,
crystalline solid: yield 84%; mp 79−82 °C; 1H NMR δ 10.10 (s, 1H),
7.92 (d, J = 8.2 Hz, 2H), 7.90 (dd, J = 8.2, 1.3 Hz, 1H), 7.80 (d, J =
8.1 Hz, 1H), 7.53 (d, J = 8.1 Hz, 2H), 7.46 (dd, J = 8.1, 7.0 Hz, 1H),
7.42−7.38 (m, 1H), 7.30−7.25 (m, 2H), 2.00 (s, 3H); 13C NMR δ
192.2, 151.9, 139.1, 135.20, 135.18, 135.0, 130.7, 130.5, 130.3, 129.8,
129.6, 129.3, 127.7, 126.0, 124.5, 25.5; FTIR (ATR) v 2933, 2716,
1699, 1600, 1207, 1167, 821, 777, 761 cm−1; LRMS (EI) m/z 246 (M+),
215, 202, 189.
and the reaction mixture was magnetically stirred under an atmosphere
of hydrogen for 5 h. The reaction mixture was diluted with additional
ethyl acetate and filtered under vacuum through a Celite pad. The
filtrate was extracted with 6 M HCl, and the resulting aqueous layer
was made basic using 50% aqueous NaOH. The solution was extracted
with ethyl acetate. Removal of solvent afforded the product as a liquid
in 80% yield: 1H NMR δ 7.80 (dd, J = 8.1, 1.4 Hz, 1H), 7.76−7.72 (m,
1H), 7.40 (dd, J = 8.1, 7.0 Hz, 1H), 7.34 (dd, J = 8.1, 7.0 Hz, 1H), 7.29
(dd, J = 7.0, 1.5 Hz, 1H), 7.22−7.19 (m, 1H), 7.10 (d, J = 8.5 Hz, 2H),
6.70 (d, J = 8.5 Hz, 2H), 3.97−3.16 (br, 2H), 2.08 (s, 3H); 13C NMR δ
145.4, 140.8, 135.9, 135.7, 135.3, 131.7, 130.6, 129.9, 129.7, 128.6,
127.5, 125.5, 124.5, 114.5, 25.3. FTIR (ATR) v 3456, 3374, 2964,
1621, 1516, 1454, 1263, 1179, 1098, 1038, 1033, 819, 774 cm−1;
LRMS (EI) m/z 233 (M+), 215, 202, 189; HRMS (DART-TOF) calcd
for C17H16N [M + H]+ 234.1283, found 234.1283.
General Procedure for X-ray Structure Determination. X-ray
data were collected at 173 K for 4b, 4c, 4e, and 4g−i, and 110 K for
4d, on a Bruker Smart Apex CCD diffractometer using graphite
monochromated Mo Kα radiation (λ = 0.71073 Å). Except for 4c,
which exhibited a positional disorder in the aldehyde functionality and
was processed separately (see the Supporting Information for details),
all data were processed with the Bruker Apex2 suite of programs.23
The frames were integrated with the Bruker SAINT software
package using a narrow-frame algorithm, and data were corrected for
absorption effects using the multiscan method (SADABS).24 The
structures were solved by direct methods and refined by full-matrix
least-squares on F2, using the Bruker SHELXTL software package.19,25
All nonhydrogen atoms were refined anisotropically, and the
hydrogens were calculated on a riding model. The software program
enCIFer26 was used in conjunction wih the checkCIF/Platon facility of
IUCr to validate cif files.
Computational Methods. Geometries of compounds 4a, 4d, 4e,
4f, and 4j were fully optimized with the Gaussian 0927 suite of
programs with the hybrid Hartree−Fock density functional theory
method (B3LYP)28 and 6-31G* basis set. Vibrational frequency
calculations, carried out at the same level of theory, allowed the
characterization of the located stationary points as minima (no
imaginary frequencies). The WP0429 functional may be invoked in
Gaussian 09 by entering the BLYP keyword and adding internal
options as follows: iop (3/76=1000001189,3/77=0961409999,3/
78=0000109999).18a The GIAO/WP04/6-31G(d) chemical shift was
scaled in accord with the following formula: scaled shift δ = (32.433 −
calculated isotropic magnetic shielding)/0.9927.18a For GIAO/WP04/
cc-pVDZ calculations, the scaled chemical shift δ = (31.844 −
calculated isotropic magnetic shielding)/1.0205.18b
4-(8-Methylnaphthalen-1-yl)benzonitrile (4d). Colorless, crys-
1
talline solid: yield 53%; mp 139−143 °C; H NMR δ 7.92−7.89 (m,
1H), 7.82−7.78 (m, 1H), 7.70 (dd, J = 7.9, 0.6 Hz, 2H), 7.47 (dd, J =
7.9, 0.6 Hz, 2H), 7.46−7.44 (m, 1H), 7.41 (dd, J = 8.1, 7.1 Hz, 1H),
7.28−7.26 (m, 1H), 7.25 (dd, J = 6.4, 0.9 Hz, 1H), 1.99 (s, 3H). 13C
NMR δ 150.3, 138.5, 135.2, 134.7, 131.61, 130.62, 130.5, 130.4, 130.0,
129.6, 127.8, 126.1, 124.5, 119.2, 111.0, 25.6; FTIR (ATR) v 2967,
−1
2224, 1605, 1454, 1367, 840, 850, 822, 774 cm ; LRMS (EI) m/z 243 (M+),
228, 215, 202, 189.
1-(4-Fluorophenyl)-8-methylnaphthalene (4e). Colorless
1
solid: yield 55%; mp 58−61 °C; H NMR δ 7.84 (dd, J = 8.2, 1.4 Hz,
1H), 7.76 (d, J = 8.1 Hz, 1H), 7.41 (dd, J = 8.1, 7.0 Hz, 1H), 7.35
(dd, J = 8.1, 7.1 Hz, 1H), 7.30−7.24 (m, 3H), 7.23−7.20 (m, 1H), 7.06
(t, J = 8.8 Hz, 2H), 2.00 (s, 3H); 13C NMR δ 162.2 (d, J = 245.5 Hz),
141.2 (d, J = 3.5 Hz), 139.4, 135.3 (d, J = 20.2 Hz), 131.24, 131.20,
131.14, 130.07, 129.9 (d, J = 1.0 Hz), 129.3, 127.7, 125.8, 124.5, 114.58
(d, J = 21.3 Hz), 25.4; FTIR (ATR) v 3040, 2971, 1602, 1511, 1494,
1212, 1157, 842, 817, 757, 726 cm−1; LRMS (EI) m/z 236 (M+), 220,
215, 202, 189.
1-(2-Fluorophenyl)-8-methylnaphthalene (4f). Clear, color-
1
less, viscous liquid: yield 13%; H NMR δ 7.89 (dd, J = 8.2, 1.4 Hz,
1H), 7.80−7.76 (m, 1H), 7.46 (dd, J = 8.2, 7.0 Hz, 1H), 7.41−7.29
(m, 4H), 7.25−7.22 (m, 1H), 7.18 (td, J = 7.5, 1.2 Hz, 1H), 7.12 (ddd,
J = 9.4, 8.3, 1.1 Hz, 1H), 2.08 (s, 3H); 13C NMR δ 160.2 (d, J =
244.0 Hz), 135.1 (d, J = 11.2 Hz), 133.5, 132.9, 132.7, 132.1 (d, J =
3.2 Hz), 131.6, 130.1 (d, J = 0.7 Hz), 129.95, 129.88, 129.3 (d, J = 7.8 Hz),
127.9, 125.7, 124.6, 123.7 (d, J = 3.6 Hz), 115.4 (d, J = 22.2 Hz), 23.9;
FTIR (neat) v 3057, 2969, 1580, 1492, 1448, 1215, 1106, 816, 773,
758 cm−1; LRMS (EI) m/z 236 (M+), 215, 220, 202, 189; HRMS
(DART-TOF) calcd for C17H14F [M + H]+ 237.1080, found 237.1067.
1-(4-Chlorophenyl)-8-methylnaphthalene (4g). Colorless,
1
crystalline solid: yield 31%; mp 73−78 °C; H NMR δ 7.85 (dd,
J = 8.2, 1.2 Hz, 1H), 7.77 (d, J = 8.1 Hz, 1H), 7.47−7.38 (m, 2H), 7.36
(d, J = 8.3 Hz, 2H), 7.28−7.22 (m, 4H), 2.03 (s, 3H); 13C NMR δ
143.6, 139.2, 135.3, 135.2, 133.0, 131.05, 131.04, 130.1, 129.8, 129.4,
127.9, 127.7, 125.8, 124.5, 25.5; FTIR (ATR) v 3035, 2968, 1595,
1485, 1088, 1013, 831, 817, 769 cm−1; LRMS (EI) m/z 252 (M+), 237,
215, 202, 189, 152, 107.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Copies of H and 13C NMR spectra, FTIR spectra, and GC−
1-Methyl-8-(p-tolyl)naphthalene (4h). Colorless, crystalline
1
MS data for compounds 4a−j. Cartesian coordinates and
energies for the B3LYP/6-31G(d) optimized structures of 4a,
4d, 4e, 4f, and 4j. Computed isotropic magnetic shielding
values and chemical shifts. Notes about the X-ray structure
determination for compound 4c. Crystallographic information
files (CIFs) for compounds 4b−e and 4g−i. This material is
available free of charge via the Internet at http://pubs.acs.org.
solid: yield 39%; mp 64−67 °C; H NMR δ 7.83 (dd, J = 8.2, 1.4 Hz,
1H), 7.77−7.74 (m, 1H), 7.42 (dd, J = 8.1, 7.0 Hz, 1H), 7.35 (dd, J =
8.1, 7.0 Hz, 1H), 7.29 (dd, J = 7.0, 1.5 Hz, 1H), 7.22 (dd, J = 6.0,
2.2 Hz, 3H), 7.19 (d, J = 7.8 Hz, 2H), 2.43 (s, 3H), 2.03 (s, 3H); 13C
NMR δ 142.4, 140.6, 136.5, 135.7, 135.2, 131.3, 129.8, 129.8, 129.7,
128.9, 128.4, 127.6, 125.6, 124.5, 25.3, 21.5; FTIR (ATR) v 2960,
1514, 1500, 1442, 1107, 1036, 1023, 819, 775 cm−1; LRMS (EI) m/z
232 (M+), 217, 215, 202, 189, 165, 101.
1-(4-Methoxyphenyl)-8-methylnaphthalene (4i). Colorless,
crystalline solid: yield 50%; mp 91−95 °C; H NMR δ 7.82 (dd,
1
AUTHOR INFORMATION
■
J = 8.1, 1.4 Hz, 1H), 7.75 (d, J = 8.1 Hz, 1H), 7.41 (dd, J = 8.1, 7.0 Hz,
1H), 7.35 (dd, J = 8.1, 7.1 Hz, 1H), 7.29 (dd, J = 7.0, 1.4 Hz, 1H),
7.25−7.20 (m, 3H), 6.92 (d, J = 8.7 Hz, 2H), 3.86 (s, 3H), 2.04 (s,
3H); 13C NMR δ 158.8, 140.3, 137.7, 135.7, 135.2, 131.5, 130.7, 129.9,
129.9, 128.9, 127.6, 125.6, 124.5, 113.1, 55.5, 25.3; FTIR (ATR) v
2955, 2928, 1606, 1515, 1490, 1438, 1239, 1183, 1174, 1033, 835, 819,
777 cm−1; LRMS (EI) m/z 248 (M+), 233, 215, 202, 189.
Corresponding Author
*E-mail: dmthamat@colby.edu.
Present Address
†Department of Chemistry, University of Wisconsin-Madison,
1101 University Avenue, Madison, Wisconsin 53706,
United States.
Synthesis of 4-(8-Methylnaphthalen-1-yl)aniline (4j). A
solution of 7b (100 mg, 0.38 mmol) in ethyl acetate (10 mL) was
degassed by bubbling with Ar. About 15 mg Pd/C was then added,
Notes
The authors declare no competing financial interest.
1699
dx.doi.org/10.1021/jo202203r | J. Org. Chem. 2012, 77, 1693−1700

The Journal of Organic Chemistry
Article
(19) For an analogous procedurefor averaging methyl chemical shifts,
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Brown, J. D. J. Am. Chem. Soc. 1998, 120, 11510.
(20) Wheeler, S. E.; Houk, K. N. J. Am. Chem. Soc. 2009, 131, 3126.
(21) Wheeler, S. E.; Houk, K. N. J. Chem. Theory Comput. 2009, 5,
2301.
(22) Mallory, F. B.; Mallory, C. W. Org. React. (Hoboken, NJ, U. S.)
1984, 30, 1.
(23) APEX2; Bruker AXS Inc.: Madison, WI, 2009.
(24) Sheldrick, G. M. SADABS; University of Gottingen: Gottingen,
Germany, 2008.
(25) Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112.
(26) Allen, F. H.; Johnson, O.; Shields, G. P.; Smith, B. R.; Towler, M.
J. Appl. Crystallogr. 2004, 37, 335.
ACKNOWLEDGMENTS
■
We gratefully acknowledge support of this work by the
National Science Foundation through Grant No. CHE-
1012914, and a grant from the SD Bechtel, Jr. Foundation to
C.W.A. We thank Professors Ned H. Martin, Paul von Rague
Schleyer, and Hans Reich for helpful discussions, and Professor
Paul Rablen for providing valuable guidance for the com-
putation of chemical shifts. We are indebted to Professor Bruce
Foxman for assistance with the X-ray structure solution of 4c
and Dr. Carlton Rauschenberg for the DART-TOF high resolution
mass spectral data.
́
(27) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
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