Through-space interactions between parallel-offset arenes at the van der Waals distance: 1,8-Diarylbiphenylene syntheses, structure and QM computations

Article abstract of DOI:10.1039/b800031j

A model for studying polar-π interactions between arenes spaced at van der Waals distances is developed on the basis of peri-diarylbiphenylenes. A set of 1,8-diarylbiphenylenes is synthesized comprising two Hammett series, one with reference to mesityl ring interactions and the other with reference to pentafluorophenyl ring interactions. X-Ray crystal structures of several derivatives are determined. Barriers to rotation of the probe aryl ring are derived from dynamic NMR data and show a trend for the mesityl reference series (ΔG^≠vs. σ°). The model is also used as a test for comparison of modern density functional methods, including B3LYP, M06-2X and BMK functionals; dispersive effects are seen to be an important factor in the proper theoretical treatment of arene interactions. the Owner Societies.

Full text of DOI:10.1039/b800031j

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Physical Chemistry Chemical Physics
This paper is published as part of a PCCP Themed Issue on:
Stacking Interactions
Guest Editor: Pavel Hobza
Editorial
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Through-space interactions between parallel-offset
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diarylbiphenylene syntheses, structure and QM
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PAPER
www.rsc.org/pccp | Physical Chemistry Chemical Physics
Through-space interactions between parallel-offset arenes at the van der
Waals distance: 1,8-diarylbiphenylene syntheses, structure and QM
computationsw
Franco Cozzi,*a Rita Annunziata,a Maurizio Benaglia,a Kim K. Baldridge,*b
Gerardo Aguirre,*c Jesus Estrada,c Yongsak Sritana-Anantd and Jay S. Siegel*b
´
Received 2nd January 2008, Accepted 19th March 2008
First published as an Advance Article on the web 16th April 2008
DOI: 10.1039/b800031j
A model for studying polar–p interactions between arenes spaced at van der Waals distances is
developed on the basis of peri-diarylbiphenylenes. A set of 1,8-diarylbiphenylenes is synthesized
comprising two Hammett series, one with reference to mesityl ring interactions and the other with
reference to pentafluorophenyl ring interactions. X-Ray crystal structures of several derivatives
are determined. Barriers to rotation of the probe aryl ring are derived from dynamic NMR data
and show a trend for the mesityl reference series (DGa vs. s1). The model is also used as a test for
comparison of modern density functional methods, including B3LYP, M06-2X and BMK
functionals; dispersive effects are seen to be an important factor in the proper theoretical
treatment of arene interactions.
lumnar stacked arenes (Fig. 1). As such, studies on 1,8-diaryl
Introduction
derivatives of biphenylene provide a new vantage point to
Through-space polar–p interactions between aromatic rings
continue to be invoked as important structural determinants in
a variety of natural and synthetic molecules.1 They have been
implicated as influencing the three-dimensional structures of
important biomacromolecules such as proteins and nucleic
acids.2 These interactions have also been extensively exploited
in the design of new drugs,3 in the formation of supramole-
cular adducts and new materials4 and in attempts to prede-
termine crystal structures.5 Because dissecting the elementary
component effects of systems like drug–receptor complexes is
prone to difficulties, much of the basis for claims of polar–p
involvement comes from parallels drawn from the statistical
analysis of protein structures, computational estimates or
physical organic model systems. Finding a model system in
which the rings were at an optimal distance has been elusive.
The 1 and 8 (peri) positions of biphenylene point in parallel
directions and sit 3.7 A apart, which matches well with the
conventional 3.6–3.8 A interplanar spacing observed for co-
investigate polar–p interactions.
Interacting arenes can adopt a continuum of different
relative orientations, which can be crudely classified by three
general classes (Fig. 2): parallel-stack (PS), parallel-offset
(PO), and edge-to-face (EF).6 In the PS disposition the surface
contact is larger than in the other cases and, accordingly, the
interaction between the aromatic systems is at its maximum.
On passing to the PO and EF arrangements, the strength of
the interaction decreases proportionally to the decreasing
contact area, to the point that the importance of the EF
interaction has sometimes been questioned.7
Several experimental studies on model systems have been
devoted to elucidating the nature and the relative importance
of the phenomena determining the aryl–aryl interaction.8 One
interpretation of these studies leads to the conclusion that
dispersive forces dominate the interaction which is then
modulated by simple and induced dipolar effects (the so-called
polar–p effect).9 Such a model is further supported by exten-
sive theoretical work predicting the repulsive nature of the PS
disposition and the attractive nature of both the PO and EF
ones.10 This combined view of experiments and theory also
allows one to understand the nature of a variety of arene–
arene interactions in very different systems.1,2
a Dipartimento di Chimica Organica e Industriale, Universita’ degli
Studi di Milano, via Golgi 19, I-20133 Milano, Italy. E-mail:
franco.cozzi@unimi.it; Fax: +39 (0)2 50314159; Tel: +39 (0)2
50314170
b Organisch-Chemisches Institut, Universitat Zurich,
¨
Wintherthurerstrasse 190, CH-8057 Zurich, Switzerland. E-mail:
¨
¨
Being aware of the fact that polar effects depend critically
on the distance between the interacting dipoles, the bipheny-
lene model, in which the arenes are located at a distance
jss@oci.uzh.ch; Fax: +41 (0)44 6356888; Tel: +41 (0)44 6354281
c
´
Centro de Graduados e Investigacion del Instituto Tecnologico de
Tijuana Unidad Mesa de Otay, Zona Industrial Apartado Postal
´
´
1166, C.P. 22000 Tijuana, B.C., Mexico. E-mail:
gaguirre@tectijuana.mx. E-mail: kimb@oci.uzh.ch
d Department of Chemistry, Faculty of Science, Chulalongkorn
University, Phayathai Road, Patumwan, Bangkok, 10330, Thailand
w Electronic supplementary information (ESI) available: Coordinates
of the primary computed structures and details of the synthesis of 3d
and 3e. CCDC reference numbers 678682 & 679270–679272. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/b800031j
Fig. 1 Geometry of (peri) 1,8-biphenylenes
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2686 | Phys. Chem. Chem. Phys., 2008, 10, 2686–2694

Fig. 2 Three classes of arene–arene interaction.
approximating the van der Waals (vdW) contact distance,
helps to refine our understanding of the polar–p contribution
to arene–arene interactions. By synthesizing compounds com-
parable to the peri-substituted naphthalene derivatives em-
ployed in previous studies9 and performing related X-ray,
NMR and computational investigations, one obtains a broad-
er view of the geometric factors influencing the polar–p effect,
on which the design of molecules whose functions and proper-
ties ostensibly depend on the interactions between aromatic
systems can be based.
Results and discussion
Ullmann coupling with pentafluoroiodobenzene to produce 4a
(X = OMe), 4b (X = H), and 4c (X = Cl) in paltry overall
yields of 6, 13 and 5% respectively.
peri-Substituted biphenylene as model system
In designing the model system a strong influence came from
previous work on 1,8-diarylnaphthalenes of general formula 1
and 2. A PS disposition of the arenes was expected, albeit with a
larger aryl–aryl separation at the ipso positions, and an almost
parallel as opposed to a splayed conformation. Two series of
compounds were targeted, 3 and 4. The ‘‘reference’’ aryl rings
were chosen as mesityl and pentafluorophenyl for dꢁ and d+
centered rings, respectively. This designation comes from ana-
logy to the quadrupolar nature of mesitylene and hexafluoro-
benzene. These reference aryl rings bear ortho and ortho0
substituents, which additionally support a locked-orthogonal
conformation between the reference ring and the biphenyene
scaffold. The variable or probe ring is either mono-ortho or
-meta substituted to provide the necessary symmetry breaking in
the static ground state while providing a dynamic symmetry that
renders sites on the reference ring equivalent during rapid
flipping of the probe ring. With this model a systematic study
of the effect of electronic substituents on the arene interaction
using variable temperature (VT) NMR is readily accessible.
Synthesis of series 3 and 4
In accordance with this model, 1,8-diarylbiphenylenes 3a–f
and 4a–c were synthesized as depicted in Scheme 1. The
synthesis of both series started from 1,8-dibromobiphenylene,
5. In series 3, Suzuki coupling of 5 with mesitylboronic acid
produced a common intermediate 1-bromo-8-mesitylbipheny-
lene 6, in which the reference mesityl ring was installed in 43%
yield. From 6, a second Suzuki coupling with the respective 4-
X-substituted-2-tolyl boronic acid produced 3a (X = OMe,
74%), 3b (X = H, 70%), 3c (X = Cl, 60%), 3d (X = CN,
50%) and 3e (X = F, 77%). Demethylation of 3a with boron
tribromide in dichloromethane produced 3f (X = OH, 93%).
In series 4, it was necessary to create three independent
monocoupled intermediates, 7a–c, via Stille coupling of 5 with
the appropriate 4-X-substituted-3-tolyl trimethylstannane.
Each of these intermediates was then subjected to standard
Scheme 1 (a) Pd(PPh3)4; (b) Pd(PPh3)4; (c) Pd2(dibenzylidene
acetone)3; (d) Cu–bronze; (e) BBr3.
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Structural studies
torsion angles (f) and (j) in combination with the out-of-
plane twisting described by the dihedral parareference ring-1-
8-paraprobe ring angle (w). One could argue that there should
be a substantial conjugation component between the indivi-
dual arene rings and the biphenylene scaffold. This effect has
been considered and found to be relatively small compared to
the steric effects.
Crystals of 3b–e (X = H, Cl, CN, F) suitable for X-ray
crystal analysisw were obtained and subjected to diffraction
analysis. A pseudo-C2 symmetry axis can be defined by
consideration of the canted orientation of both rings. The
disorder in the structure of 3e reflects this pseudo symmetry in
that the molecules pack such that a crystallographic average
C2 axis is manifested. There is also some concern about the
R factor for the structure of 3b (R = 0.16). Taken as a single
structure, the quality would be far lower than one wishes,
but in the context of a series of derivatives and the
various computational studies (see below), these additional
structures provide corroborative evidence of a common
conformational motif in which the probe ring’s ortho-methyl
group is proximal and pointing toward the reference ring.
A further consideration in favor of retaining these data is
that no abnormal geometrical parameters result from the
refinement (Table 1).11
All four structures have relatively similar geometries.
Distances a, b and c cluster around an average value of 3.80
ꢂ 0.04 A, with ip> and pr> distances around 3.52 ꢂ 0.06 A.
Overall, the rings appear close to parallel. The average of
angles a and b fall very close to the ideal 901 (avg. = 90.78 ꢂ
0.901), indicating little strain. The ring torsions f and j
average 63.5 ꢂ 2.41, favoring a PO over PS geometry, and
the average w value close to zero (avg. = 2.5 ꢂ 1.11) supports
little out-of-plane twisting of the biphenylene. Overall, it seems
clear that this model adopts a strain-free PO aryl–aryl orienta-
tion in the ground state.
The structures 3b–e were analyzed for their relative separa-
tion of reference and probe rings by considering the following
carbon-to-carbon distances: (a) biphenylene positions 1-to-8;
(b) arene ring positions ipso-to-ipso; (c) arene ring positions
para-to-para. The planar separation of the rings could also be
estimated by the orthogonal distance from the ipso- and para-
carbons of the reference ring to the mean plane of the probe
ring (ip>) and (pr>), respectively. The suitability of bipheny-
lene as a scaffold for holding the rings at a relatively un-
strained distance was gauged by the 8-1-ipsoreference ring (a) and
1-8-ipsoprobe ring (b) angles. Ideally they should be around 901
if no distortion of the bond vectors takes place. An assessment
of the preference for PS vs. PO orientation comes from the ring
Computational studies
The conformational analyses of 3a–c and 4a–c described in
this study, including structural and orbital arrangements as
well as property calculations, were carried out using the
Gaussian9812 and GAMESS13 software packages. Structural
computations of all compounds were performed using density
functional methods (DFT) as well as MP2.14 The B3LYP
method employed Becke’s 3 parameter functional15 with non-
local correlation provided by the Lee–Yang–Parr expres-
sion16,17 with local and nonlocal terms, the new M06-2X
functional18 of Zhao and Truhlar, and the BMK functional
of Boese and Martin.19 Dunning’s correlation-consistent basis
set, cc-pVDZ, a [3s2p1d] contraction of a (9s4p1d) primitive
set, was employed.20 Full geometry optimizations were
performed and uniquely characterized via second-derivative
(Hessian) analysis to determine the number of imaginary
frequencies (0 = minima; 1 = transition state) and zero-point
contributions. Molecular-orbital and electrostatic-contour
plots, used as an aid in the analysis of results, were generated
and depicted using the programs 3D-PLTORB21 and
QMView.22
Table 1 Geometry of reference and probe-ring orientations
Polarizability and vdW effects constitute a large portion of
just about all intermolecular interactions. The PS and PO
interaction between arenes certainly follows this rule.
Recently, several new computational methods have been
developed to account for such vdW effects within DFT
computations. Systems like 3a–c and 4a–c provide an excellent
testbed for these new computational methods. Specifically, the
M06-2X and BMK functionals were compared against the
classical B3LYP functional.z
3b = H 3c = Cl
Exptl
3d = CN 3e = F
Exptl
Exptl
Exptl
Geometric parameters
a/A
b/A
c/A
a/1
b/1
f/1
3.80(1)
3.89(1)
3.84(1)
90.7(4)
92.3(4)
61.0(9)
65.1(9)
3.0(2)
3.773(6)
3.815(6)
3.776(6)
90.3(2)
91.2(3)
62.1(6)
59.2(7)
3.7(1)
3.796(4)
3.824(4)
3.795(4)
89.5(1)
91.6(1)
65.2(3)
64.1(3)
0.99(8)
3.498(2)
3.483(3)
3.797(5)
3.812(5)
3.715(5)
90.3(1)
90.3(1)
65.8(3)
65.8(3)
2.4(1)
Two ground-state conformations were found, correspond-
ing to a slight canting of the aryl groups such that the methyl
of the probe ring is either endo (pointing over the reference
ring) or exo (pointing outside the reference ring). In both series
all derivatives are predicted to adopt the endo conformation
with a preference of between 2 to 5 kJ molꢁ1. This prediction
j/1
w/1
ip>a/A
pr>a/A
a
3.595(6) 3.456(4)
3.607(7) 3.481(4)
3.544(2)
3.490(3)
ip> and pr> = orthogonal distance from ipso- or para-carbon of
reference ring to mean plane of probe ring respectively; R factor for 3b
is large (0.16); structure for 3e is 2-fold disordered.
z In light of the results found here, a more complete analysis of the
theoretical methods for the treatment of p systems by the various DFT
methods could be warranted as part of a follow-on project.
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is consistent with the crystallographic forms found in
studies of the 3 series. Thus, subsequent comparisons use
the endo isomer.
Whereas the general geometric predictions of bond lengths
and angles are similar for all three methods, an analysis of the
long-range parameters that describe the inter-arene interac-
tions reveal a distinctly better performance by BMK for
predicting the geometry in series 3. Ten geometric parameters
were used to describe the nature of the inter-arene interaction
in the X-ray crystallographic structuresw (cf. Table 1). Each of
these was also derived from the 3a–c structures computed with
the M06-2X, BMK and B3LYP functionals. For the critical
interplanar stacking distance (ip>) predicted values increase
from 3.3 to 3.6 to 4.0 A for M06-2X, BMK and B3LYP
respectively—only BMK approaches the experimentally ob-
served 3.6 A (Fig. 3).
With regard to the angle (a, b) and torsion (f, j, w)
parameters, the comparison between experiment and DFT
method again clearly favors BMK. Deviation from the experi-
mental values is largest for B3LYP, followed by M06-2X, and
then BMK which provides the best prediction. From the
nature of the distortion, it appears that M06-2X overestimates
the attraction between the arenes and ends up with a tighter
PO geometry. In contrast, B3LYP underestimates the attrac-
tion between the arenes, likely because of its known inability
to handle vdW attractions. The result is PO geometrical
predictions in which the arenes are splayed apart and the
biphenylene scaffold is substantially distorted. Following this
analysis we continue our discussion of geometry using the
BMK predicted values (Fig. 4).
Fig. 4 Deviation of M06-2X (blue), BMK (yellow) and B3LYP
(green) DFT predictions from crystallographically measured angles
(a, b) and torsions (f, j, w).
rings as a function of greater donor strength; however, this
trend is extremely small and it would be dangerous to over-
interpret it.
The general computed geometry of the 3 series nicely agrees
with that found crystallographically. Overall, the rings appear
close to parallel. The average of angles a and b fall very close
to the ideal 901 (avg. = 90.42 ꢂ 0.631), slightly smaller than
that observed crystallographically (avg. = 90.78 ꢂ 0.901). The
ring torsions f and j average 62.9 ꢂ 2.11, favoring a PO over
PS geometry and the average w value close to zero (avg. 3.1 ꢂ
2.21). On the whole, the BMK functional seems to do an
excellent job in reproducing the crystallographic geometry.
A similar analysis on the 4 series predicts closer interplanar
contacts (avg. ip> and pr> = 3.34 ꢂ 0.11 A). No general trend
in the average interplanar distances as a function of structure
is present, the pr> values increase from 3.34 to 3.42 to 3.49 A
for 4a, 4b and 4c respectively, whereas the ip> values decrease
from 3.37 to 3.23 to 3.19 A, indicative of a simple tilting of the
ring orientation about a common average interplane separa-
tion. One might have expected opposing trends for the 3 and 4
series where the reference rings have opposite core polarity
(d+ vs. dꢁ); however, the effects here are extremely small, and
vdW and polarizability effects could easily swamp out polar–p
effects.
Looking at the interplanar distances ip> and pr>, BMK
computations predict an average value of 3.51 ꢂ 0.05 A for the
3 series, which is spot on with that found crystallographically.
Across the series 3a, 3b and 3c, the interplanar distances ip>
(pr>) are relatively constant, 3.52 (3.50), 3.50 (3.64) and 3.46
(3.41) respectively. A minor trend toward shorter distances is
seen for ip> consistent with a stronger interaction between the
A further caveat on inferring unique supramolecular p
effects from the 4 series comes from the analysis of its other
average structural features. While the rings still seem to be
more or less parallel and a and b angles sit close to the ideal
901 (avg. = 89.30 ꢂ 0.571), the ring torsions f and j average
50.1 ꢂ 2.01 and the w value extends to greater than 101 (avg.
12.4 ꢂ 0.61) indicating stronger conjugation interactions be-
tween the aryl rings and the biphenylene scaffold as well as
stronger out-of-plane distortions due to steric repulsion
between the probe and reference rings. In the absence of any
crystallographic data for the 4 series, the BMK predictions are
interpreted here at face value.
Fig. 3 Comparison of crystallographic (red) inter-arene distances in
A with M06-2X (blue), BMK (yellow) and B3LYP (green) DFT
predictions.
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Phys. Chem. Chem. Phys., 2008, 10, 2686–2694 | 2689

Dynamic VT NMR studies
EDG substituent (as in 3a) the ground state is destabilized
(higher in energy) and the barrier is lower. On the contrary,
introduction of an EWG substituent (as in 3c) leads to a less
destabilized ground state (lower in energy) and to a higher
barrier. The slope (r) for the plot of DGa vs. the s1 for series 3
(ca. 6.2 ꢂ 2 kJ molꢁ1 s1ꢁ1) is smaller than that observed for
series 1 when R = H and about the same as when R = Me.9
One might be concerned as to what extent these variances
come from changes in the inter-ring interactions vs. simple
conjugation as in substituted biphenyls. The variance due
to conjugation effects in the barrier to biphenyl rotations
is, however, much smaller than seen here and should bend
both ends of the series to lower barriers due to stabilization
of the transition state. This effect is discussed in more detail
in ref. 9a.
As in the 1H spectra of series 3a–f, 19F-NMR spectra of 4a–c
in CDCl2F showed single signals for the meta-fluorine atoms
at room temperature, consistently with rapid rotation around
the biphenylene–aryl bond on the NMR timescale. Upon
cooling the samples, the signals split into separated singlets
(Dd = 0.51, 0.20 and 0.66 ppm for 4a, 4b and 4c respectively),
thus showing restricted rotation. By line-shape analysis the
DGa values for the rotation around the bond connecting the
biphenylene scaffold to the probe ring were determined to be
31.3 (167 K), 30.6 (157 K) and 30.9 kJ molꢁ1 (166.5 K) for 4a,
4b and 4c respectively. Thus, the coalescence temperatures and
the rotational barriers were considerably lower for 4a–c than
for 3a–f. More importantly, the overall variation was extre-
mely small (0.7 kJ molꢁ1) and the trend was not in full
agreement with the polar–p interpretation of the interaction.
As already observed for compounds of series 2, the inverted
polarity of the perfluorinated ring should lead to a more
stabilized ground state (higher barrier) when the probe ring
is made more electron-rich by the introduction of an EDG
substituent as the MeO group in 4a; by the same token, the
barrier should decrease on passing to the H-substituted com-
pound 4b and further decrease in the case of the Cl-substituted
adduct 4c; clearly this is not the case, the barrier for 4b being
lower than that of 4a and 4c as assessed by VT-NMR
experiments. In contrast, the barrier for 4b is predicted to be
higher than that of 4a and 4c when the BMK DFT data are
considered. Overall it is safest to say that all these barriers lie
within experimental error of one another and no simple trend
can be identified or rationalized.
Having established crystallographically and computationally
that the PO conformation is preferred in the series 3 and 4, one
can probe the through-space polar–p interaction by studying
the barrier to rotation of the probe ring as a function of para
substitution (s1).23 For series 3 with a dꢁ reference ring one
should expect lower barriers for electron donating groups
(X = EDG), and higher barriers for electron withdrawing
groups (X = EWG). In contrast, for series 4 a similar
substitution should lead to the opposite effect on the barrier.
The absolute value of the slope of the plot gauges the strength
of the interaction, and the sign of the slope indicates the nature
of the reference ring (d+ vs. dꢁ). In previous studies of series 1
and 2, the observed slopes were 15 ꢂ 2 kJ molꢁ1 s1(1 R = H);
5 ꢂ 2 kJ molꢁ1 s1 (1 R = Me) and ꢁ4 ꢂ 2 kJ molꢁ1 s1 (2)
respectively.9
1H-NMR spectra of 3a–f in CDCl2F showed a single signal
for the ortho methyls of the mesityl ring at room temperature.
This observation is consistent with rapid rotation around the
biphenylene–aryl bond on the NMR timescale. Upon cooling
the samples, however, the signals split into well-separated
singlets (Dd in Hz = 77, 123, 87, 160, 145 and 103 for 3a–f
respectively), thus showing restricted rotation. By line-shape
analysis the DGa in kJ molꢁ1 for the rotation around the bond
connecting the biphenylene scaffold to the 2-tolyl ring was
determined to be 39.3 (198 K), 40.6 (208 K), 42.2 (213 K), 42.6
(220 K), 44.2 (227 K) and 39.9 (203 K) for 3a–f respectively.
A plot of DGa vs. the s1 values for the X substituents
showed a simple correlation between the variation of the
barrier and the EDG or EWG nature of the substituent
(Fig. 5). The observed trend is consistent with the polar–p
interpretation. In this context the through-space interaction
between PO arenes of similar polarity is electrostatically
repulsive. Accordingly, when the reference ring is dꢁ and the
probe ring is made more electron-rich by the presence of an
A fundamental difference between series 2 and 4 is the
distance between the aryl groups and their specific geometry.
In series 2 the aryl groups were bound to the peri positions of
naphthalene and the ipso positions were much closer to each
other (ca. 2.9 A) than the para positions (44.0 A). The
interaction was intimate and specific at the ipso positions,
with a distinctly splayed orientation of the rings. In series 4,
the aryl groups are calculated to be more uniformly parallel
(see geometry discussion above). Despite the parallel relation-
ship between the aryl groups it was noted above that the aryl-
to-biphenylene torsion angle is significantly smaller than in
other systems studied and a substantial out-of-plane twisting
of the peri positions is predicted to occur. These more dis-
torted geometries point to the possibility that factors other
than arene–arene interactions are at play.
Fig. 5 Free energies of activation in kJ molꢁ1 for 3a–f and 4a–c
plotted against s1.23 Triangles represent 3a–f; diamonds represent
4a–c. Red is derived from BMK computations; blue is derived from
VT NMR experiments. (x-Axis errors come from Taft’s estimate that
s1 values are transferable ꢂ 0.03 s units;23 y-axis errors come
primarily from errors in Tcoalescence.)
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systems for computational methods, specifically for determin-
ing the geometry and energetics of 3a–f. DFT functionals
M06-2X, BMK and B3LYP were all implemented at the basis
set cc-pVDZ. The BMK functional was found to provide
superior results for predicting geometry and barriers to rota-
tion when compared to experiment. Overall, the substituent-
modified polar–p effect is seen to be rather weak for rings not
in intimate contact. The observation and modeling of a
preferred PO geometry still supports the idea that polar–p
effects destabilize the PS geometry. Complications in the
interaction of perfluoroarene-containing derivatives indicate
that in this case secondary effects play a stronger role than
previously considered. In all such systems the vdW dispersive
and other polarizability effects must be considered.
Fig. 6 Comparison of barrier energies in kJ molꢁ1 measured by VT-
NMR (red) with M06-2X (blue), BMK (yellow) and B3LYP (green)
DFT predictions.
Experimental
General. 1H-NMR spectra were recorded at 300 or 500 MHz
in CDCl3, and were referenced to tetramethylsilane (TMS) at
0.00 ppm; peak assignments were based on direct and long-
range C–H correlations as well as on two-dimensional experi-
ments. 13C-NMR spectra were recorded at 75 or 125 MHz and
were referenced to 77.0 ppm in CDCl3. 19F-NMR spectra were
recorded at 470 MHz in CDCl2F as solvent and were refer-
enced to hexafluorobenzene at ꢁ163.00 ppm. Commercially
available reagents were used as purchased; solvents were dried
following standard purification procedures. Non-commercial
boronic acids and trimethylstannane derivatives were prepared
according to standard described procedures.
Among these, one factor that may play a role in these
systems derives from the special character of aromatic fluor-
ides. Although the polarity of the carbon(sp2)–fluorine bond is
d+ on carbon, a substantial a-effect on the p electrons keeps
the ionization potential in polyfluoroaromatics relatively con-
stant compared to their parent hydrocarbons. Additionally,
although many discussions consider the ‘‘quadrupolar’’ mo-
ment of the aryl rings, at such short distances interactions
among the individual point charges determine the actual
interaction energy. The para substituent on the probe ring
must play an influential role such that chlorine–fluorine (4c)
and oxygen–fluorine (4a) through-space interactions could
complicate the analysis.
1-Bromo-8-(2,4,6-trimethylphenyl)biphenylene (6). To a de-
gassed 9 : 1 DME–water solution (20 mL) kept under argon,
mesitylboronic acid (2.46 g, 15 mmol), 1,8-dibromobipheny-
lene (3.10 g, 10 mmol),22,24 barium hydroxide monohydrate
(2.84 g, 15 mmol) and tetrakis(triphenylphosphine)palladium
(0.347 g, 0.3 mmol) were added and the mixture was refluxed
for 18 h. Water (10 mL) was then added to the cooled mixture
and this was extracted three times with diethylether (3 ꢃ 20
mL). The combined organic phases were washed with water,
then with brine, and dried over magnesium sulfate. The
solvent was removed under vacuum and the crude product
was purified by flash-column chromatography using hexane as
eluant. The product was a pale-yellow, very thick oil (1.5 g,
43%). 1H-NMR (500 MHz, CDCl3): d 6.90 (2H, s), 6.87–6.58
(6H, m), 2.31 (3H, s), 2.15 (6H, s); 13C-NMR (125 MHz,
CDCl3): d 152.9, 151.4, 149.7, 147.8, 136.9, 136.4, 134.6, 131.9,
131.8, 131.2, 129.7, 129.1, 127.7, 116.3, 115.7, 110.1, 21.0, 20.6;
HRMS (EI+) m/z calcd for (M+) C21H17Br: 348.0514 and
350.0493; found: 348.0525 and 350.0492.
To test that the BMK function was the best choice for
predicting energies as well as geometries, the barriers for 3a–c
were determined using the M06-2X, BMK and B3LYP func-
tionals. The extreme overestimation of the barriers by M06-2X
is striking, in line with the suppositions made by inspection of
the geometries that the inter-arene attractions were overesti-
mated. Although B3LYP predictions were more reasonable
than M06-2X, only BMK-computed data fell within 1 kJ
molꢁ1 for the three systems (3a–c) studied by all three methods
(Fig. 6). Over the full series 3a–f, BMK-computed data
displayed a root mean deviation within 1 kJ molꢁ1 between
predicted and experimental values; the largest deviations
(1.5 kJ molꢁ1) were found for 3e and 3f.
Conclusions
Series 3a–f and 4a–c provide a model system for the systematic
investigation of the polar–p interaction between arenes in a PO
geometry and at vdW distance between the rings. The sensi-
tivity to substituents is reduced in these peri-substituted bi-
phenylene-based models compared to the previously studied
naphthalene systems, a major difference being the proximity
and orientation of the rings. X-Ray crystallographic dataw
demonstrate that members of the 3 series adopt the structures
expected from the model design and that barriers for 3a–f
follow the expected trend, albeit with a very slight variation in
the barriers. Series 3a–f and 4a–c further serve as excellent test
1-Mesityl-8-(4-methoxy-2-methylphenyl)biphenylene
(3a).
This product was prepared by the coupling procedure de-
scribed above from 6 (0.349 g, 1 mmol) and 4-methoxy-2-
methylphenylboronic acid (0.250 g, 1.5 mmol). Purification
involved flash chromatography with hexane as the eluant. The
1
product was a yellow solid (74% yield), mp 184–186 1C; H-
NMR (500 MHz, CDCl3): d 6.80–6.64 (5H, m), 6.59 (1H, d, J
= 8.5 Hz), 6.51 (1H, d. J = 8.5 Hz), 6.49 (2H, s), 6.31 (1H, dd,
J = 8.5, 2.5 Hz), 6.28 (1H, d, J = 2.5 Hz), 3.74 (3H, s), 2.20
(3H, s), 1.93 (3H, s), 1.90 (6H, s); 13C-NMR (125 MHz,
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CDCl3) d 158.7, 151.1, 151.0, 150.1, 136.5, 136.3, 135.3, 134.3,
132.2, 131.1, 130.8, 130.4, 130.0, 129.1, 128.2. 128.1, 127.6,
115.6, 115.5, 115.4, 114.6, 110.0, 54.8, 20.7, 20.3. 20.0; HRMS
(EI+) m/z calcd for (M+) C29H26O: 390.1984; found:
390.1973.
160.85, 152.91, 152.18, 147.16, 140.88, 140.24, 131.84, 131.30,
129.88, 129.38, 129.31, 125.86, 119.65, 115.10, 114.58, 54.76,
22.94, 21.26 ppm. Elem. anal.: found C, 90.23; H, 5.88; N,
3.51; C29H23N requires C, 90.35; H, 6.01; N 3.63.
1-Mesityl-8-(4-hydroxy-2-methylphenyl)biphenylene
(3f).
This compound was obtained as a yellow solid by demethyla-
tion of 3a with boron tribromide in dichloromethane using
standard literature procedures.25 The pure product was iso-
lated by column chromatography (93%), mp 141–144 1C; 1H-
NMR (500 MHz, CDCl3) d 6.80–6.77 (2H, m), 6.66–6.51 (7H,
m), 6.23–6.20 (2H, m), 4.36 (1H, s), 2.25 (3H, s), 1.90 (9H, br
s); 13C-NMR (125 mHz, CDCl3) d 155.59, 151.25, 151.19,
150.20, 136.79, 136.76, 153.39, 134.45, 132.22, 131.30, 130.92,
130.55, 130.38, 129.46, 128.32, 128.22, 127.76, 116.39, 115.88,
115.67, 115.56, 111.75, 20.92, 20.36, 19.95; HRMS (EI+) m/z
calc. for (M+) C28H24O: 376.1827 found: 376.1813.
1-Mesityl-8-(2-methylphenyl)biphenylene (3b). This product
was prepared by the coupling procedure described above from
6 (0.349 g, 1 mmol) and 2-methylphenylboronic acid (0.205 g,
1.5 mmol). Purification involved flash chromatography with
hexane as the eluant. The product was a yellow solid (yield
70%), mp 92–95 1C; 1H-NMR (500 MHz, CDCl3): d 6.68–6.44
(12H, m), 2.15 (3H, s), 1.90 (3H, s), 1.85 (6H, s); 13C-NMR
(125 MHz, CDCl3): d 151.1, 151.0, 150.1, 149.8, 137.4, 136.4,
135.0, 134.9, 134.1, 132.4. 131.3, 130.8, 130.2, 129.1, 128.2,
128.0, 127.7, 126.4, 124.9, 115.7, 115.6, 115.5, 20.8, 20.3, 19.8;
HRMS (EI+) m/z calcd for (M+) C28H24: 360.1878; found:
360.1875.
1-Bromo-8-(4-methoxy-3-methylphenyl)biphenylene (7a). A
stream of Ar was bubbled for 15 min through a solution of
1,8-dibromobiphenylene (0.136 g, 0.44 mmol) and 4-methoxy-
3-methylphenyl trimethylstannane (0.151 g, 0.53 mmol) in dry
DMF (10 mL). To this mixture, Pd2(dibenzylidene acetone)3
(0.045 g, 0.088 mmol) and triphenylarsine (0.108 g, 0.352
mmol) were added in this order. The mixture was then refluxed
for 20 h and then cooled at RT. Water (20 mL) was then added
and the mixture was extracted with diethylether (2 ꢃ 10 mL).
The combined organic phases were washed with water
(10 mL), dried over sodium sulfate and concentrated under
vacuum. The resulting residue was purified by flash chromato-
graphy (column diameter: 1 cm; column height: 30 cm) with
light petroleum as eluant to remove the unreacted 1,8-dibro-
mobiphenylene, then 1-bromobiphenylene and finally triphe-
nylarsine. The eluant was then changed to a 99 : 1 light
petroleum–diethyl ether mixture. With this eluant a mixture
of three products was first obtained followed by a final
fraction containing the diaryl-substituted biphenylene. The
last fraction was discarded and the mixture of three products
contained in the previous fraction was purified again by flash
chromatography (column diameter: 1 cm; column height: 30
cm) with a 9 : 1 light petroleum–DCM mixture as eluant to
afford the product (0.062 g, 40%) as a colorless solid, mp
1-Mesityl-8-(4-chloro-2-methylphenyl)biphenylene (3c). This
product was prepared by the coupling procedure described
above from 6 (0.349 g, 1 mmol) and 4-chloro-2-methylphe-
nylboronic acid (0.256 g, 1.5mmol). Purification involved flash
chromatography with hexane as the eluant. The product was a
1
pale-yellow solid (yield 60%), mp 154–155 1C; H-NMR (500
MHz, CDCl3): d 6.81–6.51 (11H, m), 2.28 (3H, s), 1.92 (3H, s),
1.88 (6H, s); 13C-NMR (125 MHz, CDCl3): d 151.1, 151.0,
149.9, 149.7, 137.3, 136.9, 135.9, 135.2, 134.1, 132.7, 131.3,
131.1, 130.9, 129.8, 129.3, 128.9, 128.4, 128.3, 127.7, 124.8,
115.9, 115.7, 21.0, 20.4, 19.9; HRMS (EI+) m/z calcd for
(M+) C28H23Cl: 394.1488; found: 394.1498.
1-Mesityl-8-(4-nitrilo-2-methylphenyl)biphenylene (3d). This
product was developed starting from 3c (0.130 g, 0.329 mmol)
and CuCN (0.295, 0.329 mmol) dissolved in HMPA, then the
mixture is heated to 225 1C under inert atmosphere for 2.5 h. It
is then cooled and a solution of NaCN is added. The product
extracted from the mixture was washed successively with H2O,
aqueous HCl, NaHCO3, aqueous NaCl and H2O, and was
then dried and concentrated. The purification involves flash
chromatography with a mixture of hexane and dichloro-
methane (7 : 3), the yellow solid obtained was crystallized in
DME–ethyl acetate (1 : 1). The product was a yellow solid
1
96–98 1C. H-NMR (300 MHz, CDCl3): d 7.40–7.32 (m, 2H),
1
(yield 50%), mp 192–194 1C; H-NMR (500 MHz, CDCl3): d
6.91–6.78 (m, 4H), 6.70–6.50 (m, 3H), 3.89 (s, 3H), 2.28 (s,
3H).13C-NMR (75 MHz, CDCl3): d 157.7, 152.9, 150.7, 147.7,
146.2, 133.6, 132.6, 131.8, 130.2, 130.1, 129.5, 129.3, 127.2,
125.9, 115.6, 115.3, 110.6, 109.7, 55.4, 16.2. Elem. anal.: found
C, 68.11; H, 4.55; C20H15BrO requires: C, 68.39; H, 4.30.
7.08–6.44 (m, 12H); 2.15 (s, 3H); 2.00 (s, 3H); 1.85 (s, 6H); 13C-
NMR (50 MHz, CDCl3): d 151.22, 150.95, 149.85, 149.21,
142.38, 137.36, 136.46, 135.07, 134.05, 131.39, 130.93, 130.22,
128.89, 128.78, 128.69, 128.54, 128.49, 128.69, 127.69, 119.15,
116.39, 115.98, 110.32. 21.00, 20.35, 19.79 ppm. Elem. anal.:
found C, 88.73; H, 6.01; F, 4.90; C28H23F requires C, 88.86; H,
6.13; F 5.02.
1-Bromo-8-(3-methylphenyl)biphenylene (7b). This product
was prepared as described above from 1,8-dibromobipheny-
lene (0.155 g, 0.5 mmol) and 3-methylphenyl trimethylstan-
nane (0.153 g, 0.6 mmol). Purification involved a first flash
chromatography (column diameter: 1 cm; column height: 30
cm) with light petroleum as eluant to afford a mixture of 1-
bromobiphenylene, 1,8-dibromobiphenylene and the product.
This mixture was then chromatographed again with the same
eluant (column diameter: 1 cm; column height: 30 cm) to
afford the pure product which was isolated as a colorless solid
in 31% yield, mp 100–103 1C. 1H-NMR (300 MHz, CDCl3): d
1-Mesityl-8-(4-fluoro-2-methylphenyl)biphenylene (3e). This
product was prepared by the coupling procedure described
previously from 6 (0.349 g, 1 mmol) and 4-fluoro-2-methyl-
phenylboronic acid (0.231 g, 1.5 mmol). Purification involved
flash chromatography with hexane as the eluant. The product
1
was a yellow solid (yield 77%), mp 92–94 1C; H-NMR (300
MHz, CDCl3): d 6.81–6.42 (m, 12H); 2.17 (s, 3H); 1.92 (s, 3H);
1.89 (s, 6H); 13C-NMR (50 MHz, CDCl3): d 168.85, 161.06,
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7.34–7.30 (m, 3H), 7.21–7.16 (m, 1H), 6.91–6.89 (m, 2H),
6.84–6.79 (m, 1H), 6.70–6.59 (m, 3H), 2,43 (s, 3H). 13C-
NMR (75 MHz, CDCl3): d 152.9, 150.9, 149.7, 146.2, 137.4,
133.8, 132.6, 130.2, 130.1, 129.6, 129.3, 128.6, 127.9, 125.7,
116.1, 115.4, 110.7, 21.5. Elem. anal.: found C, 70.97; H, 4.36;
C19H13Br requires: C, 71.04; H, 4.08.
138.4, 138.2 and 136.2 (C–F para), 137.6, 133.7, 129.6, 129.4,
129.3, 128.5, 127.8, 127.7, 127.4, 124.0, 117.4, 116.3, 116.1,
21.5. 19F-NMR (476 MHz, CDCl2F): d ꢁ143.45, ꢁ158.01,
ꢁ164.54. Elem. anal.: found C, 73.30; H, 3.42; C25H13F5
requires: C, 73.53; H, 3.21.
1-Pentafluorophenyl-8-(4-chloro-3-methylphenyl)biphenylene
(4c). This compound was prepared by the Ullmann procedure
described above starting from 7c (0.050 g, 0.141 mmol) and
pentafluoroiodobenzene (0.128 mL, 1.0 mmol). The flash-
chromatographic purification was carried out using pentane
as the eluant (column diameter: 1 cm; column height: 25 cm).
The product had Rf 0.45. It was isolated in 19% yield as a
white solid, mp 184.5–185.5 1C. 1H-NMR (300 MHz, CDCl3):
d 7.06 (d, J = 8.2 Hz, 1 H), 6.93–6.87 (m, 3 H), 6.82–6.71 (m,
5H), 2.22 (s, 3H). 13C-NMR (125 MHz, CDCl3): d 151.5,
151.4, 150.9, 147.6, 144.6 and 142.6 (C–F ortho), 141.6 and
139.6 (C–F meta), 138.3 and 136.3 (C–F para), 137.0, 135.5,
133.7, 132.4, 129.6, 129.5, 129.2, 128.7, 128.1, 125.6, 117.5,
116.6, 116.1, 21.5. 19F-NMR (476 MHz, CDCl2F): d ꢁ143.04,
ꢁ156.57, ꢁ164.09. Elem. anal.: found C, 67.67; H, 2.85;
C25H12ClF5 requires , 67.81; H, 2.73.
1-Bromo-8-(3-methyl-4-chlorophenyl)biphenylene (7c). This
product was prepared as described above from 1,8-dibromo-
biphenylene (0.155 g, 0.5 mmol) and 4-chloro-3-methylphenyl
trimethylstannane (0.173 g, 0.6 mmol). Purification involved a
first flash chromatography (column diameter: 1 cm; column
height: 30 cm) with light petroleum as eluant to afford a
mixture of 1-bromobiphenylene, 1,8-dibromobiphenylene
and the product. This mixture was then chromatographed
again with the same eluant (column diameter: 1 cm; column
height: 30 cm) to afford the pure product which was isolated as
1
a colorless solid in 26% yield, mp 99–101 1C. H-NMR (300
MHz, CDCl3): d 7.40 (s, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.30 (d,
J = 8.0 Hz, 1H), 6.94–6.79 (m, 3H), 6.67–6.62 (m, 3H), 2,45 (s,
3H). 13C-NMR (75 MHz, CDCl3): d 152.8, 150.6, 149.7, 146.3,
136.0, 135.4, 134.1, 132.7, 132.5, 131.9, 129.8, 129.7, 129.5,
128.7, 127.3, 116.3, 115.5, 110.5, 20.0. Elem. anal.: found C,
63.99; H, 3.56; C19H12BrCl requires: C, 64.16; H, 3.40.
Acknowledgements
1-Pentafluorophenyl-8-(4-methoxy-3-methylphenyl)bipheny-
lene (4a). A mixture of 7a (0.051 g, 0.146 mmol), pentafluor-
oiodobenzene (0.133 mL, 1.03 mmol) and copper–bronze
(0.093 g, 1.46 mmol) was heated at 200 1C for 44 h under
stirring in a stoppered thick-walled vial. The cooled mixture
was extracted with hot chloroform (2 ꢃ 5 mL) and filtered to
remove the insoluble materials. The filtrate was concentrated
under vacuum and the resulting residue was purified by flash
chromatography (column diameter: 1 cm; column height:
25 cm) with a light petroleum–DCM 9 : 1 mixture as eluant.
The second eluted fraction (Rf = 0.4) contained the product
which was isolated as a pale-yellow solid in 15% yield (10.3
mg), mp 180–182 1C. 1H-NMR (500 MHz, CDCl3): d
6.90–6.86 (m, 2H), 6.83–6.79 (m, 3H), 6.75 (d, J = 7.0 Hz,
1H), 6.72–6.69 (m, 2H), 6.53 (d, J = 8.2 Hz, 1H), 3.84 (s, 3H),
2.07 (s, 3H). 13C-NMR (125 MHz, CDCl3): d 157.8, 152.5,
151.5, 148.0, 146.0 and 142.6 (C–F ortho), 142.6 and 139.2
(C–F meta), 139.2 and 135.9 (C–F para), 133.5, 130.4, 129.6,
129.3, 128.3, 126.1, 125.3, 117.3, 116.0, 115.9, 113.3, 108.7,
55.2, 15.9. 19F-NMR (476 MHz, CDCl2F): d ꢁ143.35,
ꢁ158.15, ꢁ164.78. Elem. anal.: found C, 71.01; H, 3.59;
C26H15F5O requires: C, 71.24; H, 3.45.
This work was supported by the Swiss and US National
Science Foundations (KKB and JSS) as well as the CNR in
Italy (FC). Universidad Autonoma de Nuevo-Leon (Monter-
´ ´
rey, Mexico) is acknowledged for generous donations of
´
diffractometer time (GA). Don Truhlar (Univerisity of Min-
nesota) is acknowledged for generously providing access to the
M06-2X functional and computer time on the Minnesota
Supercomputer. Dr Anthony Linden is acknowledged for help
on crystallographic details.
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2694 | Phys. Chem. Chem. Phys., 2008, 10, 2686–2694