Rationally designed calix[4]arene-pyrrolotetrathiafulvalene receptors for electron-deficient neutral guests

Article abstract of DOI:10.1021/jo400502t

Four upper rim bis-monopyrrolotetrathiafulvalene-calix[4]arene conjugates 2a,b and 3a,b have been efficiently synthesized using a modular construction approach. The new compounds feature a molecular tweezer architecture with a quasi-parallel arrangement of redox-active tetrathiafulvalene (TTF) arms, which serve as the guest binding centers. Complexation studies using UV/vis binding titrations revealed a high affinity of the calixarene-TTF receptors for planar electron-deficient guests, leading to formation of deeply colored charge-transfer complexes in solution. The binding efficiency of the receptors depends on the flexibility of the calixarene scaffolds and the electronic nature of the TTF arms: the highest binding efficiency is shown by receptor 2b, featuring a highly preorganized molecular structure and an electron-rich TTF moiety.

Full text of DOI:10.1021/jo400502t

Article
pubs.acs.org/joc
Rationally Designed Calix[4]arene−Pyrrolotetrathiafulvalene
Receptors for Electron-Deficient Neutral Guests
Matthias H. Duker,† Hannes Schafer,† Matthias Zeller,‡ and Vladimir A. Azov*,†
̈
̈
†Department of Chemistry, University of Bremen, Leobener Strasse NW 2C, D-28359 Bremen, Germany
‡One University Plaza, Youngstown State University, Youngstown, Ohio 44555-3663, United States
S
* Supporting Information
ABSTRACT: Four upper rim bis-monopyrrolotetrathiafulvalene-calix[4]-
arene conjugates 2a,b and 3a,b have been efficiently synthesized using a
modular construction approach. The new compounds feature a molecular
tweezer architecture with a quasi-parallel arrangement of redox-active
tetrathiafulvalene (TTF) arms, which serve as the guest binding centers.
Complexation studies using UV/vis binding titrations revealed a high affinity
of the calixarene−TTF receptors for planar electron-deficient guests, leading
to formation of deeply colored charge-transfer complexes in solution. The
binding efficiency of the receptors depends on the flexibility of the calixarene
scaffolds and the electronic nature of the TTF arms: the highest binding
efficiency is shown by receptor 2b, featuring a highly preorganized molecular
structure and an electron-rich TTF moiety.
calixarene linkers,12b−g or for the study of metal-promoted
electron-transfer.12h,i In the only two recent reports that
describe upper rim-modified calix[4]arenes with multiple TTF
substitution,14 the tetrathiafulvalene−calixarene derivatives
were employed for anion recognition via hydrogen bonding
with amido groups, linking the TTF units to the calixarene
scaffolds. Due to cooperative effects of four proximal amido
groups very high binding constants (up to 5 × 104 M−1) were
achieved,14a and the binding process could be followed both
spectroscopically (UV/vis) as well as electrochemically.
Recently, we have reported the synthesis of calix[4]arenes 1
with two upper rim TTF bridges (Figure 1), which were also
tested as receptors for planar electron-deficient guests but were
shown to be only moderately effective.15 The low binding
affinity of receptors 1 (Figure 1), determined by NMR binding
titrations, can be attributed to two factors. First and foremost,
thioalkyl-substituted tetrathiafulvalenes, although easy to
synthesize, are relatively electron-poor TTF derivatives, which
do not afford good stabilization of electron-deficient molecules
by means of charge-transfer and π−π interactions.16 On the
other hand, weak guest complexation is also due to the rather
broad conformational space of the receptors which allows many
possible mutual orientations of the TTF arms, most of which
are not suitable for guest binding.
INTRODUCTION
■
With the advent of efficient and selective preparation methods,1
calixarenes, a family of macrocyclic compounds, have been
extensively used in various areas of supramolecular chemistry.2
They can be readily modified at the phenolic hydroxyl groups
(lower rim) as well as at the positions para to the HO-groups
(upper rim) and have proven to be superb molecular scaffolds
for the assembly of receptors for neutral and charged guests,3 as
well as of molecular capsules.4 Calix[4]arene, the smallest
member of the family, can be locked in any one of four
possible, geometrically precisely defined conformations, which
can be employed for exact control of the spatial arrangement of
the attached functional groups.5
Tetrathiafulvalenes6 (TTFs) are redox active heterocyclic
compounds that quickly found use in the field of organic
electronics7 due to their ability to form conductive phases in
the solid-state. In later years, they were widely employed as
building blocks in diverse supramolecular systems, where they
have played the role of switching units8 in different types of
molecular architectures.9 In numerous interlocked supra-
molecular devices,10 the TTF moiety has been employed as a
redox-switchable electron donor: it drastically reduces its
electron-donating properties upon oxidation and, thus, can
serve as a molecular motor inducing positional displacement of
supramolecular components.
Despite the promising prospects of combining these two
building blocks in one larger assembly, only relatively few
tetrathiafulvalene−calixarene derivatives have so far been
reported.11−14 Of these few, almost all were lower rim
calix[4]arene12 or thiacalix[4]arene13 conjugates, which were
employed for sensing of cations and anions via polar (ion-
dipole and H-bonding) interactions centered on the TTF−
To improve binding properties, the following modifications
were proposed. As a first measure, monopyrrolotetrathiafulva-
lenes (MPTTFs) were chosen as binding elements for the
proposed receptors. Pyrrolo-annealed tetrathiafulvalenes17 are
known to display good binding affinity toward electron-
Received: March 8, 2013
© XXXX American Chemical Society
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arene bowl as well as the almost free rotation around the Ar−
CH2 bond. Because of the latter, both the “closed” and “open”
pinched cone conformations can attain parallel arrangement of
two TTF units. On one hand, this gives additional flexibility to
the receptor and improves its adaptability to accommodate
guest molecules. On the other hand, this flexibility also makes
the receptor structure less preorganized for binding due to
much broader conformational space, which might make it less
specific for any particular molecular guest.
RESULTS AND DISCUSSION
■
Synthesis. Rigid receptors 2 were synthesized employing
the copper-catalyzed Ullmann-type N-arylation reaction25
between MPTTF derivatives 4a,b and Br-substituted calix[4]-
arenes (Scheme 1). Bis-alkylthio MPTTF 4a26 is quite stable
and easy to handle, whereas nonsubstituted MPTTF 4b18a is
more sensitive but was expected to render better binding with
electron-deficient species. To obtain the reference compounds
and to test the coupling reaction, which is relatively new to
pyrrolo-TTF chemistry,27 two mono-TTF derivatives 5a and
5b were first prepared in relatively good yields. The same
reaction from 5,17-dibromocalix[4]arene 6 afforded receptors
2a,b.28 In the case of 2a, the yield was rather low due to the
relative instability of the product on silica gel columns and very
similar Rf values for 2a and its monosubstituted byproduct.
Receptors 3a,b were efficiently prepared by reaction of a
deprotonated MPTTF unit with the previously reported 5,17-
dibromomethylcalix[4]arene29 derivative 7 (Scheme 2).
Figure 1. Molecular design of the calyx[4]arene-tetrathiafulvalene
receptors of the first, 1, and second, 2 and 3, generations. R1 = alkyl, R2
= SPr, H.
deficient cyclobis(paraquat-p-phenylene) macrocycles,16,18
much surpassing those of tetrakis-alkylthio TTFs. In addition,
monopyrrolo-TTFs have also been successfully employed for
the construction of TTF-calix[4]pyrrole receptors,19 which
comprised four TTF units and showed excellent binding of
planar electron-poor nitroaromatic guests between their TTF
arms, as well as in several other types of supramolecular hosts.20
As a second structure modification, we also changed the way of
TTF attachment to the calixarene backbone (Figure 1): each
monopyrrolotetrathiafulvalene unit was symmetrically ap-
pended through a single bond connecting the apex N-atom
of the pyrrole to the para-position of the calixarene phenyl
groups. To evaluate the influence of flexibility on the receptors’
efficiency, we decided to compare the directly linked “rigid”
receptor 2 with the “flexible” receptor 3, containing an
additional methylene group in the TTF-calixarene link.
The new MPTTF derivatives were obtained as bright yellow
or pale yellow crystalline powders for derivatives of 4a and 4b,
respectively. Solubility in nonpolar organic solvents, such as
CH2Cl2 or toluene, is good (all derivatives of H-MPTTF 4a) or
fairly good (derivatives of PrS-MPTTF 4b, with the exception
of poorly soluble 5b), giving solutions that are stable at room
temperature in air. Of the six newly prepared compounds, only
5a afforded crystals suitable for X-ray structural analysis.21 The
crystal structure features two crystallographically distinct
molecules, both featuring a coplanar arrangement of the TTF
and aromatic units, as predicted by modeling and observed in
other X-ray structures of related derivatives.24 In the crystal
packing, molecules are interconnected via several nonclassical
weak intermolecular hydrogen bonds and S−S interactions.
1H NMR spectra of the calixarene-MPTTF conjugates
indicate that the calix[4]arene bowl shows a preference for
one of the asymmetric pinched cone conformations, as seen
from the presence of two pronounced nonequivalent pairs of
OPr chains and differences in chemical shifts of protons
attached to pairs of diametrically opposite aromatic rings.30
Aromatic hydrogens of the p-substituted phenyl groups
(ArHsub) display a relatively strong high field shift (6.23−6.45
ppm) when compared with those of the nonsubstituted phenyls
(ArHunsub, 6.70−6.95 ppm). Pyrrolic protons of the MPTTF
moiety are also shifted upfield (6.03−6.09 ppm) in comparison
with similar signals of derivatives 5a,b (6.83−6.84 ppm). This
evidence implies that the “closed” pinched cone conformation
with quasiparallel orientation of the two aromatic rings is
preferred. The fact that only one set of signals is observed in
the 1H NMR spectra may be explained either by fast
interconversion on the NMR time scale between the two
possible pinched cone conformations with a strong preference
for the “closed” one or by slow interconversion of the same
conformers with an overwhelming prevalence for the “closed”
Molecular modeling21 using semiempirical methods showed
that receptors 2 should have only two low-lying “open” and
“closed” pinched cone conformations with a low transition
barrier between them (Figure 2). In the “closed” conformation,
Figure 2. Two possible pinched-cone conformations of 2b with (a)
closed and (b) open TTF arms (PM3). Propyl groups on calixarenes
are replaced with methyl groups.
the MPTTF arms lie almost parallel to each other at a distance
of ca. 6.5−7.5 Å, indicating a distance suitable for π-stacking
with an aromatic guest and making 2 another member of the
family of molecular tweezer-like receptors.22,23 In the “open”
conformation, the MPTTF arms are almost orthogonal to each
other, making an angle of 85°. Importantly, the planes of the
MPTTF units and adjacent aromatic rings are expected to be
coplanar, which was also observed before in several X-ray
structures of similar derivatives.24
The conformational space of 3 is defined by interconversion
between the two pinched cone conformations of the calix[4]-
1
isomer. The pattern of the H NMR signals in the aromatic
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a
Scheme 1. Synthesis of Pyrrolotetrathiafulvalene Derivatives 2 and 5
a
DACH = trans-diaminocyclohexane.
Scheme 2. Synthesis of Monopyrrolotrathiafulvalene-calix[4]arene Derivatives 3
Figure 3. Cyclic voltammograms of pyrrolo-TTF derivatives: (a) with PrS-substituted TTFs 2a, 3a, and 5a; (b) with H-substituted TTFs 2b, 3b, and
5b. CH2Cl2/0.1 M Bu4NClO4, scan rate 100 mV/s, potentials are plotted vs SCE.
region is solvent-dependent: compounds 2a, 2b, and 3b show
broadening of their ArHsub signal in CD2Cl2 and CDCl3,
whereas the same signal in the spectrum of 2a becomes sharp
upon measurement in C6D6.21,31 Such behavior implies that
“closed”−“open” conformational equilibration is relatively fast
on the NMR time scale at rt in chlorinated solvents with only
modest line broadening due to exchange processes and
significant preference for the closed conformation due to
intramolecular TTF−TTF interaction. Upon change to
benzene, which affords better TTF solubilization due to its π-
system, conformational interconversion becomes even faster,
leading to observation of sharp signals for all aromatic protons.
The UV/vis spectra of compounds 2a, 3a, and 5a (CH2Cl2,
293 K) show the common absorption pattern32 for thioalkyl-
substituted TTF derivatives with maximum absorption at λmax
of ca. 310−330 nm, as well as a shoulder at ca. 390 nm and a
long tail with low absorption reaching to ca. 500 nm. The UV/
vis spectra of 2b, 3b, and 5b display the same absorption
maximum and tailing low absorption up to 500 nm but were
missing the shoulder at 390 nm, which manifested itself in a
much paler yellow color for these derivatives.
C
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Redox Properties. The electrochemical properties of all
new MPTTF derivatives were investigated by cyclic voltam-
metry (CV) in dichloromethane/Bu4NClO4 solutions (Figure
3a,b). Mono-TTF compounds 5a,b display the classical
electrochemical behavior of tetrathiafulvalene derivatives,7c
showing two quasi-reversible electrochemical processes on the
cathodic scan, the first one leading to the TTF radical cation
and the second affording the dication. Bis-SPr-substituted 5a
shows a slightly higher first oxidation potential than 5b (Table
1), as expected due to the electron-withdrawing effect of the
between the NH protons of the host and nitro groups of the
guests. A structurally similar bis(tetrathiafulvalene)calix[2]-
pyrrole[2]thiophene receptor40 showed affinity to 7,7,8,8-
tetracyanoquinodimethane (TCNQ), although the binding
was found to be much weaker than for TTF-calix[4]pyrroles,
likely due to the lack of additional stabilization through H-
bonding interactions.
We have chosen TCNQ and TNF as test compounds for our
study, the former being a relatively compact planar molecule,
while the latter having an extended π-system and distorted
planarity due to out of plane rotation of the nitro groups.41
Initial qualitative visual experiments, performed by mixing of
diluted host and guest solutions in CH2Cl2, immediately
provided evidence for host−guest interactions. Different
degrees of color change, induced by the build up of CT
bands, were observed for different receptors. The deepest
coloration of a solution was achieved upon mixing of receptor
2b with TCNQ (strong green color, Figure 4) or TNF (dark
Table 1. Electrochemical Data of New Pyrrolo-TTF
a
Derivatives
ox1
ox2
compd
E1/2 (V)
E1/2 (V)
5a
2a
3a
5b
2b
3b
0.42
0.31
0.40
0.40
0.29
0.22
0.82
0.91
0.78
0.84
0.85
b
(0.73)
a
Data were obtained using a one-compartment cell in CH2Cl2/0.1 M
Bu4NClO4, Pt as the working and counter electrodes, and a
nonaqueous Ag/Ag+ reference electrode; scan rate 100 mV/s. Values
given at room temperature vs SCE; the Fc/Fc+ couple (0.480 V vs
b
SCE) was used as an internal reference.39 Very weak oxidation wave.
two thioalkyl groups.16,33 Rigid receptors 2a,b display a
broadening of the first oxidation waves and their shift to
lower oxidation potentials in comparison to their correspond-
ing mono-TTF counterparts 5. These effects are often observed
in CVs of TTF derivatives with two or several spatially proximal
tetrathiafulvalene groups12d,34,35 and are explained by the
formation of mixed valence TTF dimers (TTF−TTF•+),36
stabilized by intramolecular charge transfer (CT) interaction.
The flexible PrS-substituted receptor 3a shows usual redox
behavior, very similar to that of 5a, whereas the voltammog-
ramm of its nonsubstituted counterpart 3b is rather
uncommon. The CV of 3b presents one strong low-lying
oxidation potential, presumably leading to two mono-
oxidations of the two MPTTF groups, while only a very
small wave is observed at the position of the expected second
oxidation potential. Additionally, the peak separation ΔEp is
larger than for other monopyrrolotetrathiafulvalene derivatives
and grows rapidly with increasing sweep rate,21,37 indicating the
irreversibility of the electron-transfer process. The nature of this
irreversibility has not been yet clarified. We speculate that this
effect may be due an intramolecular reaction, such as pyrrole
electrodimerization,38 between two spatially proximal MPTTF
moieties. The reversibility for both oxidation processes for
other bis-MPTTF derivatives can be explained as follows:
compounds 2a and 3a possess deactivated PrS-substituted
MPTTF moieties, while in compound 2a and 2b MPTTFs are
rigidly attached to the calix[4]arene backbone, making the
attainment of a suitable mutual orientation for such a tentative
dimerization impossible.
Figure 4. Change of solution color upon formation of charge-transfer
complexes between 2b and 7,7,8,8-tetracyanoquinodimethane
(TCNQ) or 2,4,7-trinitro-9-fluorenylidenemalononitrile (TNF) in
CH2Cl2. [Guest] ≈ [host] ≈ 0.3 × 10−3 M. The structures of TCNQ
and TNF are shown.
brown color). Receptor 2a was second in efficiency, while other
MPTTF derivatives showed rather limited (bis-derivatives
3a,b) or almost no color changes (monoderivatives 5a,b),
even at higher concentrations.
All new TTF derivatives, as well as the guest compounds, do
not show any notable absorption above 500 nm. Titration of
TCNQ solution with 2a results in appearance of two strong CT
band centered at λmax = 748 and 850 nm, whereas for TNF a
very broad absorption band beginning below 500 nm and with
a maximum above 1100 nm (beyond the measurement range of
our instrument) is observed (Figure 5).
Binding studies42 were performed by UV/vis binding
titrations in CH2Cl2 to determine the binding constants Ka
and extinction coefficients ε of the CT complexes. The results
(Table 2) gave us insight into the influence of electron-
donating properties of differently substituted MPTTFs and of
receptors’ rigidity/flexibility on their affinity toward the two
structurally different guest compounds. First, receptors 2b and
3b with nonsubstituted MPTTF arms are stronger binders than
their counterparts 2a and 3a, containing deactivated PrS-
substituted MPTTF units. Second, rigid and highly preor-
ganized receptors 2a,b display higher binding constants than
flexible receptors 3a,b. More detailed examination of the
binding constants shows that the binding efficiency of flexible
receptors 3a,b toward TNF decreases much less than toward
TCNQ, when compared with receptors 2a,b. Thus, receptors 2
are much stronger binders of TCNQ than of TNF, which
Binding Studies. Receptors 2a,b adopt quasiparallel
orientation of the two MPTTF arms, which make them similar
to tetrathiafulvalene−calix[4]pyrrole receptors,19 which showed
good binding affinity toward electron-deficient 2,5,7-trinitro-9-
dicyanomethylenefluorene (TNF) and 1,3,5-trinitrobenzene
(TNB). Binding was due to CT intermolecular interactions,
as well as additional stabilization, provided by H-bonding
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Figure 5. Absorption spectra of (a) TCNQ (constant concentration of 0.5 × 10−3 M, CH2Cl2) recorded upon variation of the concentration of 2b
(0−1.25 × 10−3 M); (b) TNF (constant concentration of 1.0 × 10−3 M, CH2Cl2) recorded upon variation of the concentration of 2b (0−3.0 × 10−3
M).
Table 2. Binding Properties of the Pyrrolo-TTF Receptor
Derivatives
from two different calixarene backbones and two monop-
yrrolotetrathiafulvalenes and using a modular assembly
approach. The rigid preorganized calixarene-MPTTF molecular
receptors 2a,b show strong binding with TCNQ and TNF in
solution, giving deeply colored CT complexes, whereas the
flexible receptors 3a,b are, overall, less efficient. The remarkable
color change upon formation of CT complexes makes the
observation of the binding process straightforward to follow
and the incorporation of the guest is readily sensed. Such
MPTTF−calixarene molecular tweezers possess a high
modification potential and should serve as a starting point for
design and construction of a variety of novel receptor
architectures.
a
b
compd
Ka, M−1 (ε850, M−1cm−1) with TCNQ
Ka, M−1 with TNF
2a
2b
3a
3b
750 (4200)
3000 (3200)
110 (600)
160 (910)
170
670
75
500
a
Data were obtained in CH2Cl2 solution using UV/vis binding
b
titrations at room temperature. 850 nm is the absorption maximum
for CT complexes of TCNQ with receptors 2a,b and 3a,b.
manifests itself also by much higher extinction coefficients of
their CT complexes in comparison with 3. On the other hand,
the binding efficiency of receptors 3 toward TNF is almost the
same (3a) or even stronger (3b) than toward TCNQ. Such an
interesting behavior can be rationalized by a slight nonplanarity
of the TNF molecules, making them too thick to fit into the
relatively narrow gap of 2. Moreover, molecular modeling
provided qualitative evidence for better stacking between the
MPTTF arms and TNF guest in case of receptor 3.21
Overall, receptor 2b, the best binder in the new family of
MPTTF−calix[4]arene receptors, shows binding constants
similar to those of the MPTTF−calix[4]pyrrole receptors,19
even though, in the case of receptors 2, the binding was due
only to CT and π−π interactions without any further
stabilization via additional host−guest H-bonds. Such a high
binding affinity confirms the feasibility of our receptor design
and paves the way for a variety of additional modifications,
which can be readily implemented due to the versatility of
calix[4]arene chemistry. On the upper calixarene rim, the 4-fold
MPTTF substitution offers itself as a possibility for additional
receptor improvement. Upon proper modifications of the lower
rim, it will be possible to render solubility in polar solvents and
introduce metal-binding sites or anchor groups for surface
immobilization into the receptor structures. In addition, a
comprehensive search will be performed to identify other
suitable electron-deficient guests.43 Moreover, the redox nature
of the TTF moieties introduces an opportunity to control the
guest binding process via their oxidation or reductio, or, vice
versa, to sense the binding processes via electrochemical means.
EXPERIMENTAL SECTION
■
General Methods. 5,17-Dibromo-25,26,27,28-tetra(1-propoxy)-
calix[4]arene 6,28 5,17-dibromomethyl-25,26,27,28-tetra(1-propoxy)-
calix[4]arene 7,29 and TTF derivatives 4a17c,26 and 4b18a were
prepared as reported previously. Reagent-grade chemicals and solvents
(including absolute DMF and dioxane) were used without further
purification unless stated otherwise. All reactions were carried out
under an atmosphere of dry N2. Sodium hydride was used as a 60%
slurry in oil and washed with pentane before use. Chemical shifts (δ)
are reported in parts per million (ppm) relative to TMS; the residual
solvent signals were used as reference: CDCl3 (7.26 ppm for 1H, 77.0
ppm for 13C), CD2Cl2 (5.32 ppm for H, 53.8 ppm for 13C), or C6D6
1
1
1
(7.15 ppm for H, 128.0 ppm for 13C). H NMR coupling constants
(J) are reported in hertz (Hz), and multiplicity is indicated as follows:
br (broadened), s (singlet), d (doublet), t (triplet), q (quartet), quin
(quintet), sext (sextet), sept (septet), or m (multiplet). High-
resolution ESI-MS-spectra (HRMS) were measured with a Thermo
Fisher Scientific LTQ Orbitrap spectrometer. UV/vis measurements
were performed in a 1 cm path length quartz optical cell. Binding
constants were determined by means of UV/vis binding titrations.21
Cyclic voltammetry (CV) measurements were performed in a three-
electrode single-compartment cell.21
The X-ray structure of 5a was solved by direct methods and refined
by full-matrix least-squares analysis using SHELXTL44 and ShelXle.45
All non-hydrogen atoms were refined with anisotropic ADPs. One of
the propyl groups is disordered over two alternative positions with an
occupancy ratio of 0.877(2) to 0.123(2). The minor moiety was
restrained to have a similar geometry as the major one, and ADPs of
equivalent atoms in both moieties were constrained to be identical.
Reflection 0 0 1 was obstructed by the beam stop and was omitted
from the refinement.
CONCLUSIONS
In conclusion, a family of upper rim calix[4]arene−monop-
yrrolotetrathiafulvalene receptors has been prepared, starting
■
Melting points were determined using a capillary melting point
apparatus and are uncorrected. Rf values were determined using 0.2
mm silica gel F-254 TLC cards; the plates were inspected under UV
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light. Flash chromatography (FC) was carried out using 230−440
mesh (particle size 36−70 μm) silica gel.
5,17-Bis[2-(1,3-dithiol-2-ylidene)-5H-1,3-dithiolo[4,5-c]-
pyrrol-5-yl]-25,26,27,28-tetra(1-propoxy)calix[4]arene 2b. Pre-
pared from 4b (0.058 g, 0.24 mmol), CuI (0.016 g, 0.084 mmol),
K3PO4 (0.153 g, 0.72 mmol), trans-diaminocyclohexane (10 μL, 0.083
mmol), and 6 (0.068 g, 0.091 mmol) in 2 mL of dioxane. The crude
product was purified by flash chromatography (CH2Cl2/cyclohexane,
gradient 1:3 → 1:2, 1% Et3N) to afford pale yellow crystals. Yield: 24
mg (0.0223 mmol, 25%). Mp: 189−193 °C. Rf = 0.22 (CH2Cl2/
Pyrrolo-TTF−calixarene Coupling: General Procedure. A
heavy-walled Schlenk tube equipped with a wide bore Teflon stopcock
was charged with 4a or 4b, CuI, K3PO4, ( )-trans-1,2-diaminocyclo-
hexane, aromatic bromide (4-bromoanisole or calix[4]arene 6), and
absolute dioxane. The reaction mixture was degassed by three freeze−
pump−thaw cycles, and the vessel was filled with nitrogen, sealed, and
stirred at 110 °C for 18−24 h. The progress of the reaction was
controlled by TLC, and samples were taken under a counter flow of
nitrogen. When the reaction was complete, the mixture was filtered
through a plug of Celite, and the solvent was removed under reduced
pressure. The crude product was purified by flash chromatography on
silica gel to afford pure products 5a,b and 2a,b.
1
cyclohexane, 1:3). H NMR (360 MHz, CDCl3): δ 6.98−6.84 (m,
6H), 6.22 (bs, 8H), 6.06 (s, 4H), 4.47 (d, 2J = 13.3 Hz, 4H), 3.99 (t, 3J
= 7.9 Hz, 4H), 3.73 (t, 3J = 7.2 Hz, 4H), 3.16 (d, 2J = 13.3, 4H), 1.98
3
3
3
(sext, J = 7.9 Hz, 4H), 1.90 (sext, J = 7.2 Hz, 4H), 1.07 (t, J = 7.2
Hz, 6H), 0.94 (t, J = 7.2 Hz, 6H). 13C NMR (90 MHz, CDCl3): δ
3
157.2, 153.9, 135.8, 135.3, 128.8, 126.6, 122.49, 121.7, 119.5, 118.4,
110.2, 77.2, 31.0, 23.4, 23.0, 10.6, 9.9. UV/vis (CH2Cl2): λmax (ε) 312
nm (31000 L·mol−1·cm−1), 422 (900). MS (ESI+): m/z 1074 (100)
[M]+•, 1097 (10) [M + Na]+. MS (ESI−): m/z 1073 (100) [M − H]−,
1031 (30) [M − Pr]−. HRMS (ESI+): m/z [M]+ calcd for
2-[4,5-Bis(propylthio)-1,3-dithiol-2-ylidene]-5-(4-methoxy-
phenyl)-5H-1,3-dithiolo[4,5-c]pyrrole 5a. Prepared from 4a
(0.054 g, 0.138 mmol), CuI (0.012 g, 0.063 mmol), K3PO4 (0.082
g, 0.386 mmol), trans-diaminocyclohexane (7.5 μL, 0.062 mmol), and
4-bromoanisole (0.038 g, 0.204 mmol) in 2 mL of dioxane. The crude
product was washed with pentane to remove unreacted bromoanisole
and purified by flash chromatography (CH2Cl2/cyclohexane, 1:1) to
afford bright yellow crystals. X-ray quality crystals were grown by slow
diffusion of hexane into a benzene solution. Yield: 49.6 mg (0.10
+
C56H54N2O4S8 1074.18438, found 1074.18432. CV (vs SCE,
ox1
ox2
CH2Cl2): E1/2 = 0.29 V, E1/2 = 0.85 V.
5,17-Bis[[2-[4,5-bis(propylthio)-1,3-dithiol-2-ylidene]-5H-
1,3-dithiolo[4,5-c]pyrrol-5-yl]methyl]-25,26,27,28-tetra(1-
propoxy)calix[4]arene 3a. Pyrrolo-TTF 4a (250 mg, 0.64 mmol)
was dissolved in absolute DMF (40 mL) and degassed by a freeze−
pump−thaw cycle. The reaction mixture was then cooled with an ice
bath, and NaH (65 mg 1.63 mmol) was added, followed by 7 (226 mg,
0.29 mmol) in 5 mL of absolute THF (dried over Ph2CO/Na before
use). The mixture was allowed to warm to rt and stirred for an
additional 3 h. Then the mixture was slowly added to ca. 400 mL of
brine and extracted three times with ca. 100 mL of CH2Cl2. The
organic phase was dried (Na2SO4) and concentrated under reduced
pressure. The crude product was purified by flash chromatography
(CH2Cl2/cyclohexane, 2:3) to afford bright yellow crystals. Yield: 174
mg (0.124 mmol, 43%). Mp: 225−227 °C. Rf = 0.53 (CH2Cl2/
cyclohexane 1:1). 1H NMR (360 MHz, CDCl3): δ 6.69−6.79 (m, 6H),
1
mmol, 72%). Mp: 159−163 °C. Rf = 0.73 (CH2Cl2). H NMR (200
MHz, CD2Cl2): δ 7.22−7.30 (m, 2H), 6.91−6.99 (m, 2H), 6.84 (s,
3
3
2H), 3.82 (s, 3H), 2.81 (t, J = 7.2 Hz, 4H), 1.66 (sext, J = 7.2 Hz,
4H), 1.01 (t, 3J = 7.2 Hz, 6H). 13C NMR (50 MHz, CD2Cl2): δ 158.4,
134.2, 129.9, 127.9, 122.1, 121.4, 119.4, 115.0, 111.8, 55.9, 38.5, 23.5,
13.2. UV/vis (CH2Cl2): λmax (ε) 309 nm (24900 L·mol−1·cm−1), 328
(24900), 450 sh (1100). MS (EI): m/z 497 (100) [M]+, 454 (10) [M
− Pr]+•, 421 (20) [M − SPr]+. HRMS (EI): m/z [M]+ calcd for
+
C21H23NOS6 497.01040, found 497.00895. CV (vs SCE, CH2Cl2):
ox1
ox2
E1/2 = 0.42 V, E1/2 = 0.82 V.
2-(1,3-Dithiol-2-ylidene)-5-(4-methoxyphenyl)-5H-1,3-
dithiolo[4,5-c]pyrrole 5b. Prepared from 4b (0.075 g, 0.308 mmol),
CuI (0.021 g, 0.107 mmol), K3PO4 (0.194, 0.914 mmol), trans-
diaminocyclohexane (12.5 μL, 0.104 mmol), and 4-bromoanisole
(0.093 g, 0.495 mmol) in 2 mL of dioxane. The crude product was
washed with pentane to remove unreacted bromoanisole and purified
by flash chromatography (CH2Cl2/cyclohexane, 1:1, 1% Et3N) to
afford pale yellow crystals. Yield: 55.7 mg (0.159 mmol, 52%). Mp:
2
6.44 (s, 4H), 6.05 (s, 4H), 4.50 (s, 4H), 4.44 (d, J = 13.1 Hz, 4H),
3
3
2
3.92 (t, J = 7.6 Hz, 4H), 3.78 (t, J = 7.4 Hz, 4H), 3.14 (d, J = 13.1
3
3
Hz, 4H), 2.81 (t, J = 7.2 Hz, 8H), 1.99 (sext, J = 7.6 Hz, 4H), 1.91
3
3
3
(sext, J = 7.2 Hz, 4H), 1.67 (sext, J = 7.2 Hz, 8H), 1.05 (t, J = 7.4
Hz, 6H), 1.02 (t, J = 7.2 Hz, 12H), 0.97 (t, J = 7.2 Hz, 6H). 13C
NMR (90 MHz, CDCl3): δ 156.5, 156.1, 135.2, 134.9, 129.2, 128.4,
127.6, 127.4, 122.4, 120.0, 118.5, 112.5, 110.6, 77.2, 53.8, 38.2, 30.8,
23.3, 23.1, 13.2, 10.4, 10.1. UV/vis (CH2Cl2): λmax (ε) 283 nm (37800
L mol−1 cm−1), 328 (32000), 403 sh (2600), 452 sh (1100). MS
(ESI+): m/z 1398 (100) [M]+•, 1421 (40) [M + Na]+. HRMS (ESI+):
3
3
1
175−181 °C. Rf = 0.42 (CH2Cl2/cyclohexane, 1:1). H NMR (200
MHz, CDCl3): δ 7.22−7.30 (m, 2H), 6.91−6.99 (m, 2H), 6.83 (s,
2H), 6.37 (s, 2H), 3.81 (s, 3H). 13C NMR (50 MHz, CD2Cl2): δ
158.4, 134.3, 122.1, 121.9, 119.0, 115.0, 111.7, 55.9. UV/vis (CH2Cl2):
λmax (ε) 309 nm (23000 L·mol−1·cm−1), 321 (23500), 425 sh (460).
MS (EI): m/z 349 (100) [M]+•, 334 (5) [M − Me]+•. HRMS (EI):
+
m/z [M]+ calcd for C70H82N2O4S12 1398.29176, found 1398.29178.
ox1
ox2
CV (vs SCE, CH2Cl2): E1/2 = 0.40 V, E1/2 = 0.78 V.
5,17-Bis[[2-(1,3-dithiol-2-ylidene)-5H-1,3-dithiolo[4,5-c]-
pyrrol-5-yl]methyl]-25,26,27,28-tetra(1-propoxy)calix[4]arene
3b. Pyrrolo-TTF 4b (88 mg, 0.36 mmol) was dissolved in abs DMF
(5 mL) and degassed by a freeze−pump−thaw cycle. The reaction
mixture was then cooled with an ice bath, and NaH (37 mg, 0.92
mmol) was added followed by 7 (120 mg, 0.15 mmol) in 2 mL of abs
THF (dried over Ph2CO/Na before use). The mixture was allowed to
warm to rt and stirred for additional 3 h. Then the mixture was slowly
added to 100 mL of brine and extracted three times with 25 mL of
CH2Cl2. The organic phase was dried (Na2SO4) and concentrated
under reduced pressure. The crude product was purified by flash
chromatography (CH2Cl2/cyclohexane, 1:1, 1% Et3N) to afford pale
yellow crystals. Yield: 61 mg (0.055 mmol, 37%). Mp: 219−220 °C. Rf
+
m/z [M]+ calcd for C15oHx111NOS4 348.97235, found 348.97299. CV
ox2
(vs SCE, CH2Cl2): E1/2 = 0.40 V, E1/2 = 0.84 V.
5,17-Bis[2-[4,5-bis(propylthio)-1,3-dithiol-2-ylidene]-5H-1,3-
dithiolo[4,5-c]pyrrol-5-yl]-25,26,27,28-tetra(1-propoxy)calix-
[4]arene 2a. Prepared from 4a (0.101 g, 0.258 mmol), CuI (0.017 g,
0.089 mmol), K3PO4 (0.166 g, 0.782 mmol), trans-diaminocyclohex-
ane (10 μL, 0.083 mmol), and 6 (0.074 g, 0.099 mmol) in 2 mL of
dioxane. The crude product was purified by flash chromatography
(CH2Cl2/cyclohexane, 1:2) to afford bright yellow crystals. Yield: 59.3
mg (0.043 mmol, 44%). Mp: 118−122 °C. Rf = 0.29 (CH2Cl2/
cyclohexane, 1:3). 1H NMR (360 MHz, C6D6): δ 6.75 (s, 6H), 6.43 (s,
4H), 6.04 (s, 4H), 4.49 (d, 2J = 13.3 Hz, 4H), 3.84 (t, 3J = 7.6 Hz, 4H),
3.78 (t, 3J = 7.6 Hz, 4H), 3.09 (d, 2J = 13.3, 4H), 2.59 (t, 3J = 7.2 Hz,
1
= 0.41 (CH2Cl2/cyclohexane 1:1). H NMR (360 MHz, CDCl3): δ
3
3
8H), 1.90 (sext, J = 7.2 Hz, 4H), 1.88 (sext, J = 7.2 Hz, 4H), 1.48
(sext, 3J = 7.2 Hz, 8H), 0.94 (t, 3J = 7.2 Hz, 6H), 0.92 (t, 3J = 7.2 Hz,
6H), 0.79 (t, 3J = 7.2 Hz, 12H). 13C NMR (90 MHz, C6D6): δ 156.9,
154.8, 136.5, 135.3, 134.9, 128.8, 128.1, 122.9, 122.4, 120.6, 119.8,
110.7, 110.4, 77.2, 77.1, 38.2, 31.4, 23.6, 23.5, 23.3, 13.2, 10.5, 10.4.
UV/vis (CH2Cl2): λmax (ε) 308 nm (44000 L·mol−1·cm−1), 324
(41000), 450 sh (1100). MS (ESI+): m/z 1370 (100) [M]+. HRMS
6.71−6.82 (m, 6H), 6.43 (s, 4H), 6.32 (bs, 4H), 6.03 (s, 4H), 4.48 (bs,
4H), 4.43 (d, 2J = 13.3 Hz, 4H), 3.92 (t, 3J = 7.6 Hz, 4H), 3.77 (t, 3J =
2
3
7.4 Hz, 4H), 3.14 (d, J = 13.3 Hz, 4H), 1.99 (sext, J = 7.6 Hz, 4H),
1.90 (sext, 3J = 7.4 Hz, 4H), 1.02 (t, 3J = 7.4 Hz, 6H), 0.96 (t, 3J = 7.4
Hz, 6H). 13C NMR (90 MHz, CDCl3): δ 156.6, 156.0, 135.3, 134.8,
129.2, 128.5, 127.7, 122.5, 118.8, 118.6, 112.4, 77.2, 53.7, 30.9, 23.3,
23.1, 10.4, 10.1. UV/vis (CH2Cl2): λmax (ε) 292 nm (27000 L mol−1
cm−1), 321 (25000), 423 sh (1300). MS (ESI+): m/z 1102 (100)
[M]+•, 1125 (15) [M + Na]+. MS (ESI−): m/z 1101 (100) [M − H]−,
+
(ESI+): m/z [M]+ calcd for C68H78N2O4S12 1370.26046, found
1370.26032. CV (vs SCE, CH2Cl2): E1/2ox1 = 0.31 V, E1/2ox2 = 0.91 V.
F
dx.doi.org/10.1021/jo400502t | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1059 (30) [M − Pr]−. HRMS (ESI+): m/z [M]+ calcd for
(7) (a) Wudl, F. Acc. Chem. Res. 1984, 17, 227−232. (b) Bryce, R. M.
Adv. Mater. 1999, 11, 11−23. (c) Bendikov, M.; Wudl, F.; Perepichka,
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+
C58H58N2O4S8 1102.21568, found 1102.21687. CV (vs SCE,
ox1
ox2
CH2Cl2): E1/2 = 0.22 V (E1/2 = 0.73 V).
́
(8) Canevet, D.; Salle, M.; Zhang, G.; Zhang, D.; Zhu, D. Chem.
Commun. 2009, 2245−2269.
ASSOCIATED CONTENT
■
(9) (a) Bryce, M. R.; Devonport, W.; Goldenberg, L. M.; Wang, C.
Chem. Commun. 1998, 945−951. (b) Bryce, M. R. J. Mater. Chem.
2000, 10, 589−598. (c) Nielsen, M. B.; Lomholt, C.; Becher, J. Chem.
Soc. Rev. 2000, 29, 153−164. (d) Becher, J.; Jeppesen, J. O.; Nielsen,
K. Synth. Met. 2003, 133−134, 309−315. (e) Nielsen, M. B.;
Diederich, F. Chem. Rev. 2005, 105, 1837−1867.
S
* Supporting Information
X-ray data, NMR spectra, and signal assignment for the new
compounds, CV experimental details, descriptions of binding
experiments, and molecular modeling. This material is available
free of charge via the Internet at http://pubs.acs.org.
(10) (a) Pease, A. R.; Jeppesen, J. O.; Stoddart, J. F.; Luo, Y.; Collier,
C. P.; Heath, J. R. Acc. Chem. Res. 2001, 34, 433−444. (b) Moonen, N.
AUTHOR INFORMATION
■
́
N. P.; Flood, A. H.; Fernandez, J. M.; Stoddart, J. F. Top. Curr. Chem.
Corresponding Author
*E-mail: vazov@uni-bremen.de.
2005, 262, 99−132. (c) Klajn, R.; Stoddart, J. F.; Grzybowski, B. A.
Chem. Soc. Rev. 2010, 39, 2203−2237.
(11) Regnouf-de-Vains, J.-B.; Salle,
Perkin Trans. 2 1997, 2461−2462.
(12) (a) Zhao, B.-T.; Blesa, M.-J.; Mercier, N.; Le Derf, F.; Salle,
Org. Chem. 2005, 70, 6254−6257. (b) Zhao, B.-T.; Blesa, M.-J.;
Mercier, N.; Le Derf, F.; Salle, M. New J. Chem. 2005, 29, 1164−1167.
(c) Blesa, M.-J.; Zhao, B.-T.; Allain, M.; Le Derf, F.; Salle,
M. Chem.
M.; Balandier, J.-
́
M.; Lamartine, R. J. Chem. Soc.,
Notes
The authors declare no competing financial interest.
́
M. J.
ACKNOWLEDGMENTS
́
■
́
M.H.D. is grateful to BFK NaWi, University of Bremen, for
financial support. We are indebted to Dr. T. Dulcks and Ms. D.
Kemken (MS) and Mr. J. Stelten (NMR) for their help with the
characterization of the new compounds. The X-ray diffrac-
tometer was funded by NSF Grant No. 0087210, Ohio Board
of Regents Grant No. CAP-491, and by Youngstown State
Eur. J. 2006, 12, 1906−1914. (d) Lyskawa, J.; Salle,
́
̈
Y.; Le Derf, F.; Levillain, E.; Allain, M.; Viel, P.; Palacin, S. Chem.
Commun. 2006, 2233−2235. (e) Zhao, B.-T.; Blesa, M.-J.; Le Derf, F.;
́
Canevet, D.; Benhaoua, C.; Mazari, M.; Allain, M.; Salle, M.
Tetrahedron 2007, 63, 10768−10777. (f) Lyskawa, J.; Canevet, D.;
Allain, M.; Salle, M. Tetrahedron Lett. 2010, 51, 5868−5872. (g) Zhao,
B.-T.; Zhu, X.-M.; Peng, Q.-M.; Yan, Z.-N.; Le Derf, F.; Salle, M. Cent.
́
́
University. We also thank Dr. Rafael Gomez Aspe (Universidad
Complutense, Madrid) for helpful discussions.
́
Eur. J. Chem. 2011, 9, 1102−1108. (h) Sun, F.; Hu, F.; Zhang, G.;
Zheng, Q.; Zhang, D. J. Org. Chem. 2011, 76, 6883−6888. (i) Sun, F.;
Hu, F.; Zhang, G.; Zhang, D. Chem. Asian J. 2012, 7, 183−189.
DEDICATION
■
(13) Zhao, B.-T.; Zhou, Z.; Yan, Z.-N.; Belhadj, E.; Le Derf, F.; Salle,
́
Dedicated to Professor Fredric M. Menger (Emory University)
on the occasion of his 75th birthday.
M. Tetrahedron Lett. 2010, 51, 5815−5818.
(14) (a) Lee, M. H.; Cao, Q.-Y.; Kim, S. K.; Sessler, J. L.; Kim, J. S. J.
Org. Chem. 2011, 76, 870−874. (b) Flídrova,
Lang, K.; Lhotak, P. Dyes Pigm. 2011, 92, 668−673.
(15) Duker, M. H.; Gomez, R.; Vande Velde, C. M. L.; Azov, V. A.
́ ́
K.; Tkadlecova, M.;
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