Racemisation dynamics of torsion angle restricted biphenyl push-pull cyclophanes

Article abstract of DOI:10.1039/c0ob00650e

The thermodynamics of the atropisomerisation of torsion angle restricted, axial chiral biphenyl-based push-pull cyclophanes were studied. Using ¹H NMR coalescence measurements the rotation barrier around the central C-C bond was determined to be 50 kJ mol^-1 for the propyl-bridged biphenyl derivative 1b, displaying only a negligible solvent dependence. By protonation of the piperidinyl nitrogen as electron donor, the free energy ΔG^?(T) of the rotation barrier increased, indicating that the tendency of the push-pull system to planarise may be considered as a driving force for the atropisomerisation. For the more restricted butyl-bridged cyclophane 1c a rotation barrier of ΔG ^?(T) = 90 kJ mol^-1 was measured using dynamic chromatography. The difference in the free energy of rotation around the central C-C bond probably reflects the crowdedness of the transition states.

Full text of DOI:10.1039/c0ob00650e

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PAPER
Racemisation dynamics of torsion angle restricted biphenyl push-pull
cyclophanes
Ju¨rgen Rotzler,a Heiko Gsellinger,a Markus Neuburger,a David Vonlanthen,a Daniel Ha¨ussinger*a and
Marcel Mayor*a,b
Received 31st August 2010, Accepted 22nd October 2010
DOI: 10.1039/c0ob00650e
The thermodynamics of the atropisomerisation of torsion angle restricted, axial chiral biphenyl-based
push-pull cyclophanes were studied. Using 1H NMR coalescence measurements the rotation barrier
around the central C–C bond was determined to be 50 kJ mol-1 for the propyl-bridged biphenyl
derivative 1b, displaying only a negligible solvent dependence. By protonation of the piperidinyl
nitrogen as electron donor, the free energy DG‡(T) of the rotation barrier increased, indicating that the
tendency of the push-pull system to planarise may be considered as a driving force for the
atropisomerisation. For the more restricted butyl-bridged cyclophane 1c a rotation barrier of DG‡(T) =
90 kJ mol-1 was measured using dynamic chromatography. The difference in the free energy of rotation
around the central C–C bond probably reflects the crowdedness of the transition states.
the application of an electric field to cause a noncentrosym-
Introduction
metric arrangement of dissolved dipoles15,16 (EFISH: electric-
The interaction of matter with light and especially the possibility
field-induced second-harmonic generation measurements) or the
to manipulate light by the design of matter is one of the most
incorporation of the push-pull systems into noncentrosymmetric
structures such as poled polymer films, self-assembled films17 or
crystals.18–20 It is also known that crystal packing or supramolec-
ular assembly of such materials can enhance the physical output
dramatically.21,22
Recently, studies about torsion angle restricted biphenyl-based
push-pull systems were published where the influence of the
chromophore’s delocalization on the hyperpolarizability was in-
vestigated by EFISH measurements.23 The investigated 2 and 2¢
position alkyl-bridged biphenyl-based cyclophanes 1a–1d are axial
chiral and therefore consist of a racemic mixture of two atropiso-
mers (Fig. 1). In crystallography, it is well known that optically
pure enantiomers tend to crystallise in noncentrosymmetric point
groups, whereas racemic mixtures especially of donor-p-acceptor
exciting topics in science. Among such structurally engineered
matter are second-order non-linear optic (NLO) materials, which
have the ability to double the frequency of incoming laser light.1,2
Such NLO active materials have attracted considerable attention
because of their potential applications in telecommunication
techniques, namely high-bandwidth optical switching and pro-
cessing devices, as well as in dynamic image processing or in
the development of new laser tools.3–5 Nevertheless this growing
field of active research is still in its infancy. In the last decades
a variety of different organic NLO materials were investigated
following a donor–chromophore–acceptor structural motif.6–10
Despite the fact that great progress in understanding the influence
of different structural parts of such push-pull systems on the non-
linear optical activity has been made and molecules with large
hyperpolarizabilities have been published,11–13 the transformation
of these microscopic scale NLO active molecules to the macro-
scopic level still causes serious problems for their application.14
Two main physical properties are crucial for a strong non-
linear optic response, which are a large hyperpolarizability of the
chromophore and a noncentrosymmetric centre. This molecular
noncentrosymmetry, which can be obtained by rational design
of non-linear optic active compounds, can be transferred to the
macroscopic scale by an external physical input. Examples include
Fig. 1 (A) Sketch of the concept to restrict the interphenyl torsion angle
by an additional interlinking alkyl chain of various lengths; (B) The two
atropisomers of 1c (structures calculated with a MM2 basic set) and the
rotation around the central C–C bond showing the atropisomerisation
process.
aDepartment of Chemistry, University of Basel, St. Johannsring 19, 4056
Basel, Switzerland. E-mail: marcel.mayor@unibas.ch; Fax: +41-61-267-
1016; Tel: +41-61-267-1006
bInstitute of Nanotechnology, Karlsruhe Institute of Technology, P. O. Box
3640, 76021 Karlsruhe, Germany
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molecules crystallise in a centrosymmetric fashion since their
dipoles force such an arrangement (Fig. 2). Therefore the described
push-pull systems 1a–1d are potential candidates to realise such
a transformation of the noncentrosymmetry from a molecular
level to the macroscopic scale by enantiomeric resolution and
subsequent crystal growth.
Materials and methods
General
The syntheses of the herein investigated in 2 and 2¢ position
bridged 4-nitro-4¢-piperidinyl-biphenyls 1a–1d were previously
reported.23 In short, molecules 1a–1d were assembled by applying
a general synthetic pathway starting from their corresponding
dibromo- or ditriflate derivatives 2a–2d (Scheme 1).30 These
torsion angle restricted biphenyl building blocks were converted
into their diamino-biphenyl derivatives 3a–3d by a Hartwig–
Buchwald hetero-cross-coupling reaction using benzophenone
imine as an ammonia synthon and subsequent hydrolysis. Selective
microwave-assisted azacycloalkylation with 1,5-dibromopentane,
followed by mild microencapsulated oxidation of the remaining
free amine to a nitro functionality provided the desired push-pull
systems 1a–1d.
Solid state structure
Fig. 2 Centrosymmetric pairwise arrangement of the P (right) and M
(left) atropisomers of the push-pull derivative 1c in the solid state.
Single crystals of cyclophane 1c suitable for X-ray analysis were
obtained upon slow evaporation of a solution of 1c in a mixture
of iPrOH and hexane. The racemic mixture of 1c crystallised in
the monoclinic, centrosymmetric space group C2/c. One unit cell
consists of 8 molecules with alternating M and P enantiomers of
1c (Fig. 2).† In Fig. 3 an ORTEP presentation of the P enantiomer
of 1c is displayed.
To gain further insight into the conformational stability
of the non-linear active cyclophanes 1a–1d and to check if
it is possible to separate the two atropisomers, the rotation
barrier around the central C–C bond moved into the focus of
interest.
† Crystal data and structure refinement for cyclophane 1c: The crystal
was measured on a Bruker Kappa Apex2 diffractometer at 123 K using
For such thermodynamic studies mainly three different experi-
mental methods are applicable. Coalescence measurements by 1H
NMR,24 dynamic chromatography25–29 and monitoring the change
in the optical rotation of a chiral non-racemic mixture. For the
latter, separated enantiomers are required, whereas the first two
methods can easily be performed using racemic mixtures of the
molecules under investigation. Fast dynamic molecular processes
can be investigated by NMR spectroscopy, whereas dynamic
chromatography is more suitable for isomerisation studies of more
conformationally stable compounds. Herein, the enantiomeri-
sation dynamics of torsion angle restricted biphenyl push-pull
cyclophanes 1a–1d are reported to obtain further insight into their
dynamic behaviour and the interaction of the two phenyls under
these conditions.
˚
graphite-monochromated Mo-Ka-radiation with l = 0.71073 A, Hmax
=
27.655◦. Minimal/maximal transmission 0.99/0.99, m = 0.083 mm-1. 1c
formula C21H24N2O2, M = 336.43 g mol-1, F(000) = 1440, yellow block,
size 0.070 0.130 0.290 mm3, monoclinic, space group C2/c, Z = 8, a =
◦
◦
˚
˚
˚
25.437(6) A, b = 10.510(2) A, c = 17.615(5) A, a = 90 , b = 132.55(2) , g =
◦
3
-3
˚
90 , V = 3469.1(18) A , Dc = 1.288 Mg m . The Apex2 suite has been used
for data collection and integration. From a total of 21 978 reflections, 4017
were independent (merging r = 0.111). From these, 2392 were considered
as observed (I > 2.0s(I)) and were used to refine 226 parameters. The
structure was solved by direct methods using the program SIR92. Least-
squares refinement against F was carried out on all non-hydrogen atoms
using the program CRYSTALS. R = 0.0533 (observed data), wR = 0.1511
(all data), GOF = 1.0519. Minimal/maximal residual electron density =
-3
˚
-0.31/0.33 e A . Chebychev polynomial weights were used to complete
the refinement. Plots were produced using Mercury 2.3 and ORTEP3 for
Windows.
Scheme 1 (a) Benzophenone imine, Pd2(dba)3·CHCl3, BINAP, NaOtBu, toluene, 80 ◦C, 4 h, then 3% aq. HCl, THF, rt, 2 h, 80%–quant.; (b) benzophenone
imine, Pd(OAc)2, BINAP, Cs2CO3, THF, 65 ◦C, 17 h, then 3% aq. HCl, THF, rt, 2 h, 80%–quant.; c) 1,5-dibromopentane, K2CO3, toluene–EtOH: 1/1,
MW, 150 ◦C, 40 min, 34–44%; (d) NaBO3·4H2O, H3PW12O40, CTAB (hexadecyltrimethylammonium bromide) (10 cmc in water), 55–60 ◦C, 16 h, 45–64%.
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dynamic HPLC experiments before a set of temperature dependent
measurements was performed. The studies were performed at
temperatures between 10 and 25 ◦C in 5 ◦C steps. Three different
samples of 1c were measured twice in a row. The forward reaction
rate constants k1 were evaluated with the unified equation32 valid
for such first order processes by direct integration of the elution
profiles by the software program DCXplorer33 developed by O.
Trapp. The Gibbs free activation energy DG‡(T) was calculated by
estimation of the activation enthalpy DH‡ of the enantiomerisation
process from the slope of the Eyring plot (ln (k1/T) vs. 1/T) and
the activation entropy DS‡ from the intercept.
Results and discussion
Fig. 3 Solid state structure of the P enantiomer of 1c. Thermal ellipsoids
are set at the 50% probability level.
The interconversion of the two atropisomers of cyclophanes 1a–
1d can be monitored by NMR coalescence experiments if the
half-lives of the enantiomers are in the range of microseconds
to seconds. In this case, at temperatures below the coalescence
temperature, the exchange between the two enantiomeric forms is
slow compared to the NMR time scale (“slow exchange”) and the
diastereotopic protons on a CH2-group in the alkyl bridge have dif-
ferent chemical environment and, hence, give rise to two separate
signals. In contrast, at temperatures higher than the coalescence
(“fast exchange”), an averaged signal is observed for the two
methylene protons. Determination of the coalescence temperature
and the difference in chemical shift of the diastereotopic methylene
protons allows calculation of the Gibbs free activation energy
for the racemisation at the coalescence temperature, DG‡(Tc)
using a modified form of the Eyring equation (see Experimental
Section). In order to compare the appropriate chemical shifts,
it is necessary to have an unambiguous assignment for all
protons of the cyclophanes in the slow exchange regime. This was
accomplished by two-dimensional proton–proton and proton–
carbon correlation experiments (COSY, NOESY, HMQC).
NMR studies
Samples of 1b (10 mM) were prepared in deuterated solvents
(>99.8% D, Cambridge Isotope Laboratories, Burgdorf, CH). All
NMR experiments were performed on a Bruker DRX-600 NMR
spectrometer, equipped with a self-shielded z-axis pulsed field
gradient dual broadband inverse probe-head. Chemical shifts were
referenced to residual solvent peaks and the temperature was cali-
brated using a methanol sample.31 To ensure thermal equilibrium
at the various temperatures, at least 15 min of equilibration time
was allowed for each temperature step. Unambiguous resonance
assignment was obtained by two-dimensional COSY, NOESY
and HMQC experiments. The acquisition in the direct dimension
was performed using 2048 points (170 ms) in all cases. For the
indirect dimension 512 increments were measured, corresponding
to 85 ms, 85 ms and 40 ms, respectively. The NOE mixing time
was set to 1 s. The total experiment times were 60 min, 93 min
and 20 min, respectively. For each solvent, several experiments
with 10 K temperature steps were performed in order to estimate
the coalescence temperature. The activation energy was calculated
from the following form of the Eyring equation (eqn (1)):
The coalescence temperature (Tc) of the push-pull system shown
in Fig. 4 (1b) was measured in different solvents to obtain changes
in the activation energy due to solvent effects. As the chemical
shifts for 1b can be solvent dependent, the coalescence temperature
must also show a variation with the solvent, even in the case
DG = 0.0191Tc(9.97 + log(Tc/Dn))
(1)
Dynamic HPLC
For the determination of the free energy of rotation DG‡ around
the central C–C bond of the biphenyl-based push-pull system
1c, temperature dependent dynamic HPLC was performed. An
approximately 1 mg mL-1 solution of compound 1c in iPrOH
was prepared. 1 mL of this solution was injected into a chiral
CHIRALPAK AD-H column (0.46 ¥ 25 cm; Daicel Chemical
Industries Ltd.) at the defined temperature (CTO-10AS VP oven
from Shimadzu). The atropisomers were eluted with a mixture
of 97 : 3 of n-hexane and iPrOH (SCL-10A VP HPLC from
Shimadzu) at a flow rate of 0.5 mL min-1. To guarantee an
efficient mixing of both solvents the eluent was prepared as a 94 : 6
mixture of n-hexane and iPrOH–n-hexane 1 : 1. This premixing
procedure turned out to be required due to the poor solubility
of 1c at low concentrations of iPrOH in n-hexane. For detection
of the chromatogram a UV/vis detector (SPD-M10A VP from
Shimadzu) operating at the absorption maxima of the compound
under investigation was used (lmax = 270 nm and 371 nm). The
column was preconditioned for 10 h under the conditions used for
Fig. 4 Stacked plot of the low temperature 1H NMR spectra of 1b
measured in CDCl3. Starting from fast exchange at 298 K, reaching the
coalescence temperature at 252 K, ending in the slow exchange at 233 K
where the signals for the four protons are separated.
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Table 1 Coalescence temperatures of the push-pull system 1b (Fig. 1) in
different solvents with their characteristic separation Dn and the resulting
Gibbs activation energy
prior to the analysis. A chromatogram with two separated peaks
is expected in the case of a fixed torsion angle of the compounds
under investigation when they are separated on a chiral stationary
phase. When racemisation occurs on the chromatographic time
scale a temperature dependent plateau formation between the two
peaks is expected. A third case that can occur in dynamic HPLC
is peak coalescence. This occurs when the enantioconversion is
significantly faster than the chromatographic separation process.40
Hence, we tried to separate the two atropisomers of 1c and 1d by
chiral HPLC. Screening of several cellulose- and amylose-derived
HPLC columns revealed that the enantiomers of 1c showed a
tendency to separate on Chiralpak AD-H. At 20 ◦C the two peaks
could be separated by approximately 2 min when the compound
was eluted with a mixture of n-hexane–iPrOH 97 : 3 at a flow rate
of 0.5 mL min-1. Furthermore, plateau formation between the
two peaks was observed pointing at the expected interconversion
process of atropisomers (Fig. 6). The UV/vis spectra of the two
distinctive peaks in the chromatogram and the plateau were the
same (Fig. 5), indicating the presence of only one compound
and therefore verifying the presence of two atropisomers. The
rate constant of enantioconversions can be directly calculated
from these typical chromatograms by iterative comparison of
experimental and simulated chromatograms.
Solvent
Tc/K
Dn/Hz
DG‡/kJ mol-1
DDG‡
DMF d7
Toluene d8
Toluene d8
Benzene d6
TFA d1
MeOD d4
CDCl3
249
248
242
—
278
257
252
250
144
102
60
48.5
49.0
48.9
—
53.9
49.8
49.6
49.3
0.5
0.5
0.5
—
0.5
0.5
0.5
0.5
—
180
174
120
108
C2D2Cl4
of unchanged activation parameters. It is, however, possible that
differences in the solvation of the sterically demanding transition
state of the racemisation lead to differences in the activation
energy. The results of the measurements of 1b in different solvents
are shown in Table 1.
It was possible to record NMR spectra below and above as
well as exactly at the coalescence temperature for most solvents
used. Only the melting point of benzene was too high, so that
further cooling was not feasible. For toluene, two Tc values for
two different sets of resonances were observed. The two different
data sets lead to the very same activation energy, as expected.
As seen in Table 1, the influence of different solvents on the
activation energy is not very pronounced. The polarity of the
solvent does not seem to significantly influence the activation
energy for the interconversion of the enantiomers. Only in the case
of strongly protic conditions (trifluoroacetic acid), a significantly
higher activation energy was obtained. This is most likely due
to the protonation of the amine group, leading to a pull-pull,
rather than a push-pull substitution pattern. In a pull-pull system,
the tendency to form a conjugated and, therefore, nearly planar
arrangement will be less pronounced compared to the push-
pull case, where this resonance stabilisation factor determines
the racemisation energy.34 Additionally, two electron-withdrawing
groupsreducethep-electrondensityatthe1and1¢positions, which
makes an out-of-plane bending of the axis bond more difficult
and therefore becomes the dominating contribution to the energy
barrier.35,36 In turn, a higher activation is necessary to force the
cyclophane to racemisation.
In the case of the ethyl-bridged biphenyl 1a, it was not possible
to lower the temperature far enough (<230 K) to reach the
coalescence in any solvent. In marked contrast, for compounds
1c and 1d there was no fast exchange regime obtained, even when
heating was continued to 353 K in deuterated tetrachloroethane,
consistent with findings of earlier studies on unsubstituted
biphenyl cyclophanes.37,38 In addition, 2D-EXSY experiments at
the elevated temperature indicated that the rate constant of the
atropisomerisation has to be below 10-2 s-1.39
As mentioned above, it was not possible to determine the
rotation barrier of the C–C bond of the butyl- and pentyl-bridged
biphenyl derivatives 1c and 1d by coalescence measurements using
1H NMR spectroscopy. Careful analysis of the 1H NMR spectra
clearly showed a fixed torsion angle for both push-pull systems.
Another useful method to estimate isomerisation energies in cases
where NMR spectroscopy fails is dynamic chromatography.25–29 As
previously described for such investigations only minute sample
amounts are required and stereoisomers do not have to be isolated
Fig. 5 Representative chromatogram of push-pull cyclophane 1c, sep-
arated by a Chiralpak AD-H column eluting with a mixture of n-hex-
ane–iPrOH 97 : 3 and a flow rate of 0.5 mL min-1 at 25 ◦C. In the third
dimension the UV/vis spectra of the separated parts are shown.
Thanks to the remarkable work of Schurig27 and Trapp,33,41 pow-
erful computer simulation tools are now available. The simulation
programs profit from the so-called “theoretical plate model”,26
its statistical description namely the “stochastic model”41 or
more recently the “unified equation”32 to determine the rate
constants of enantiomerisation. Temperature dependent dynamic
chromatography gives access to thermodynamic data by applying
the Eyring equation (eqn (2)).
k1 = (kBT)/h exp(-DG/RT)
(2)
Thus, temperature dependent dynamic HPLC experiments were
performed for compound 1c. Repeated series of measurements
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Table 2 Kinetic data of 1c obtained from the elution profiles by compar-
ison of simulated and experimental elution profiles
T/K
298.2
293.2
288.2
283.2
k1/s-1a
9.25 ¥ 10-4
6.44 ¥ 10-4
4.21 ¥ 10-4
2.75 ¥ 10-4
a Average values of five repeated measurements.
were performed between 10 ◦C and 25 ◦C in 5 ◦C steps. To over-
come reproducibility problems the column was preconditioned
for 10 h operating at the desired conditions. After two series
the conditioning was repeated and the measurements were then
performed again with a different sample of the same compound.
A statistical evaluation was then performed. Peak coalescence or
baseline separation were not observed in this temperature range.
By computer simulations, using the DCXplorer software,33 of the
experimentally obtained elution profiles (Fig. 6) the enantiomeri-
sation rate constants at different temperatures were obtained
(Table 2). Since enantiomerisations are degenerate processes k1
and k-1 were assumed to be equal.
Fig. 7 Eyring plot for the atropisomerisation of 1c: temperature de-
pendent dynamic HPLC measurements analysed by linear regression.
The upper and lower curves represent the error bands of the linear
regression with a level of confidence of 95%. For the linear regression,
four measurements for each temperature were considered.
between 50 kJ mol-1 obtained for the 7-membered ring derivative
1b and 90 kJ mol-1 obtained for the 8-membered cyclophane 1c.
By comparison of the rotational energy barriers of the torsion
angle restricted biphenyl-based push-pull cyclophanes 1a–1d it is
obvious that the butyl-bridged system 1c is the conformationally
most stable compound of the series followed by the pentyl-bridged
derivative 1d. Compound 1c atropisomerises with a half life time
t
1/2 of 12.5 min which means that this compound can be assumed
to have a fixed torsion angle in most physical investigations such as
EFISH measurements. For the propyl-bridged push-pull system 1b
this is not the case since the energy barrier for atropisomerisation
is relatively low and therefore, depending on the time frame of the
experiment, isomerisation can take place during measurements
which would lead to a distribution of different torsion angles
and therefore to an averaged torsion angle over the course of
the experiment. The same is true for the ethyl-bridged derivative
1a which is even more flexible than 1b.
To explain this rather unexpected grading in enantiomerisation
energies, we hypothesise a sterically more crowded transition
through a planar, linear conformation in the isomerisation process.
Linearity of the biphenyl core can be assumed since partial double-
bond character of the central C–C bond was observed in the
crystal structure of the 2 and 2¢ position unsubstituted push-pull
system. This means that the longer the alkyl-bridge, the closer
the methylene groups have to pass by each other in the planar
conformation. The pentyl-bridge in system 1d seems to have too
many degrees of freedom and hence it can arrange in a sterically
more favourable fashion to allow isomerisation in an energetically
more convenient way.
Fig. 6 Selected experimental enantiomerisation profiles of push-pull
cyclophane 1c at different temperatures on Chiralpak AD-H using a
mixture of n-hexane–iPrOH 97 : 3 as eluent.
With the unified equation obtained, enantiomerisation rate
constants of 1c were plotted according to the Eyring equation
(ln(k1/T) versus 1/T). By linear regression analysis (Fig. 7), DH‡
was found to be DH‡ = 54.5 3.9 kJ mol-1 and DS‡ = -120 14 J
‡
K-1 mol-1. From this, DG‡ was calculated to be DG298 K = 90.3 0.2
kJ mol-1, which is in the region of 2-phenyl-2¢-isopropylbiphenyl
and 2-cyclohexyl-2¢-phenylbiphenyl (both approx. 91 kJ mol-1)
but above the rotational energy barrier of 2,2¢-dimethylbiphenyl
(approx. 78 kJ mol-1) and below that of 2,2¢-diisopropylbiphenyl
(approx. 110 kJ mol-1) reported by C. Wolf.42
Conclusion
Unfortunately, such an investigation for the pentyl-bridged
biphenyl-based push-pull system 1d was not possible by dynamic
chromatography as coalescence was observed even at low tempera-
tures. Thus, an enantioconversion faster than the chromatographic
separation process can be assumed. Since H NMR coalescence
measurements showed a fixed conformation of the two phenyls
In summary, the rotational energy barrier of 1b (3-nitro-9-
(piperidin-1-yl)-6,7-dihydro-5H-dibenzo[a,c]cycloheptene) was
‡
1
estimated to be DG298 K = 50 kJ mol-1 by H NMR coalescence
measurements. Using computer simulation of experimentally
obtained temperature dependent dynamic HPLC elution profiles
the barrier of rotation of 1c (3-nitro-10-(piperidin-1-yl)-5,6,7,8-
1
‡
of compound 1d, it is obvious that the free energy of rotation is
tetrahydrodibenzo[a,c]cyclooctene) was determined to be DG298 K
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= 90 kJ mol-1. The rotational energy barrier of 1a (1-(7-nitro-
9,10-dihydrophenanthren-2-yl)piperidine) and 1d (3-nitro-11-
(piperidin-1-yl)-6,7,8,9-tetrahydro-5H-dibenzo[a,c]cyclononene)
could only be evaluated qualitatively by comparing them with the
two quantitatively analysed derivatives 1b and 1c.
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Unfortunately, the separation of the two atropisomers failed for
all non-linear optically active compounds 1a–1d, and thus it was
not possible to grow noncentrosymmetric crystals. Nevertheless,
we obtained insight in the conformational stability of our systems
1a–1d. For compound 1a, the rotation around the central C–C
bond is rather fast and so the system has to be considered to be
flexible. Also, the rotation around the central axis of the propyl-
bridged push-pull cyclophane 1b is quite fast at room temperature.
Depending on the physical experiment, compound 1c and 1d can
be assumed as torsion angle fixed systems when the experimental
timescale is in the region of seconds. Nevertheless, the maximal
possible torsion angle was defined by bridging the biphenyl core
with alkyl chains. Motivated by these results, it will now be
of interest to determine the rotational energy barrier of 2,2¢-
alkyl-bridged and 4 and 4¢ position donor-substituted biphenyl
systems and 4,4¢-diacceptor-substituted biphenyl systems which
are available in our group and have already been investigated in
single molecule conductance measurements.30,43,44
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National Science Foundation and the National Center of Com-
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