A pyrrolo-tetrathiafulvalene cage: Synthesis and X-ray crystal structure

Article abstract of DOI:10.1021/ol026816h

(equation presented) A novel type of tetrathiafulvalene-cage 4 containing three monopyrrolo-tetrathiafulvalene units has been prepared employing a general and efficient synthetic approach. X-ray crystal structure analysis revealed that the cage is able to

Full text of DOI:10.1021/ol026816h

ORGANIC
LETTERS
2002
Vol. 4, No. 24
4189-4192
A Pyrrolo-Tetrathiafulvalene Cage:
Synthesis and X-ray Crystal Structure
,†
Kent A. Nielsen,† Jan O. Jeppesen,* Eric Levillain,‡ Niels Thorup,§ and
,†
Jan Becher*
Department of Chemistry, UniVersity of Southern Denmark (Odense UniVersity),
CampusVej 55, DK-5230, Odense M, Denmark, Department Inge´nierie Mole´culaire et
Mate´riaux Organiques, CNRS UMR 6501, UniVersite´ d’Angers, 2 Bd LaVoisier,
F-49045 Angers, France, and Department of Chemistry, The Technical UniVersity of
Denmark, DK-2800, Lyngby, Denmark
jbe@chem.sdu.dk
Received August 29, 2002
ABSTRACT
A novel type of tetrathiafulvalene-cage 4 containing three monopyrrolo-tetrathiafulvalene units has been prepared employing a general and
efficient synthetic approach. X-ray crystal structure analysis revealed that the cage is able to accommodate solvent molecules within a cavity
in the solid state.
Cyclophanes1,2 are fundamentally important compounds in
many aspects of macrocyclic and supramolecular chemistry,
and research in this field has expanded rapidly in recent
years. Tetrathiafulvalene3 (TTF) and its derivatives have been
intensively studied during the past two decades, because of
their unique π-electron donor properties. They were origi-
nally prepared for the development of electrically conducting
materials and have, as such, been synonymous with the
development of molecular organic metals. However, during
the past few years, the utility of TTF derivatives as building
blocks in macrocyclic and supramolecular chemistry has
revealed that the TTF moiety is useful3c-e,4 beyond the field
of materials chemistry and it has been incorporated into
elaborate molecular devices such as sensors,4b,c,h shuttles,4d,f
† University of Southern Denmark (Odense University).
‡ Universite´ d’Angers.
§ The Technical University of Denmark.
(4) (a) Jeppesen, J. O.; Perkins, J.; Becher J.; Stoddart J. F. Org. Lett.
2000, 2, 3547-3550. (b) Le Derf, F.; Levillain, E.; Trippe´, G.; Gorgues,
A.; Salle´, M.; Sebastian, R. M.; Caminade, A. M.; Majoral, J. P. Angew.
Chem., Int. Ed. 2001, 40, 224-227. (c) Le Derf, F.; Mazari, M.; Mercier,
N.; Levillain, E.; Trippe´, G.; Riou, A.; Richomme, P.; Becher, J.; Garin,
J.; Orduna, J.; Gallego-Planas, N.; Gorgues, A.; Salle´, M. Chem. Eur. J.
2001, 7, 447-455. (d) Jeppesen, J. O.; Perkins, J.; Becher J.; Stoddart J. F.
Angew. Chem., Int. Ed. 2001, 40, 1216-1221. (e) Collier, C. P.; Jeppesen,
J. O.; Luo, Y.; Perkins, J.; Wong, E. W.; Heath, J. R.; Stoddart, J. F. J.
Am. Chem. Soc. 2001, 123, 12632-12641. (f) Jeppesen, J. O.; Becher, J.;
Stoddart J. F. Org. Lett. 2002, 4, 557-560. (g) Luo, Y.; Collier, C. P.;
Jeppesen, J. O.; Nielsen, K. A.; Delonno, E.; Ho, G.; Perkins, J.; Tseng,
H.-R.; Yamamoto, T.; Stoddart, J. F.; Heath, J. R. ChemPhysChem 2002,
3, 519-525. (h) Trippe´, G.; Levillain, E.; Le Derf, F.; Gorgues, G.; Salle´,
M.; Jeppesen, J. O.; Nielsen, K.; Becher, J. Org. Lett. 2002, 4, 2461-
2464.
(1) (a) Vo¨gtle, F., Ed. Cyclophanes I. In Topics in Current Chemistry;
Springer: Berlin, Germany, 1983; Vol. 113. (b) Vo¨gtle, F., Ed. Cyclophanes
II. In Topics in Current Chemistry; Springer: Berlin, Germany, 1983; Vol.
115. (c) Vo¨gtle, F. Cyclophane Chemistry; Wiley: Chichester, UK, 1993.
(2) (a) Diederich, F. Cyclophanes. In Monographs in Supramolecular
Chemistry; Fraser Stoddart, J., Ed.; The Royal Society of Chemistry:
London, UK, 1991. (b) Vo¨gtle, F.; Seel, C.; Windscheif, P.-M. Compre-
hensiVe Supramolecular Chemistry; Atwood, J. L., Davies, J. E. D.,
MacNicol, D. D., Vo¨gtle, F., Suslick, K. S., Eds.; Pergamon: New York,
1996; Vol. 2, Chapter 7, pp 211-265.
(3) (a) Garin, J. AdV. Heterocycl. Chem. 1995, 62, 249-304. (b) Schukat,
G.; Fangha¨nel, E. Sulfur Rep. 1996, 18, 1-294. (c) Bryce, M. R. J. Mater.
Chem. 2000, 10, 589-598. (d) Nielsen, M. B.; Lomholt, C.; Becher, J.
Chem. Soc. ReV. 2000, 29, 153-164. (e) Segura, J. L.; Mart´ın, N. Angew.
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10.1021/ol026816h CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/07/2002

2 (Figure 1)swhich only possesses three attachment sitess
and we have very recently succeeded in preparing a TTF-
belt 3 (Figure 1) devoid of cis/trans problems. Although the
neutral belt 3 has a cavity between the two TTF moieties it
was not able to accommodate electron-deficient guest, such
as 7,7,8,8-tetracyano-p-quinodimethane (TCNQ), within this
molecular cavity.10 One solution to this problem might be
to enlarge the cavity surrounded by TTF moieties and design
cyclophanes containing more than two TTF moieties.
Here, we report such an accomplishment and describe a
general and efficient method for the preparation of TTF-
cages employing the monopyrrolo-TTF building block 2,
together with a crystal structure analysis of the TTF-cage 4.
Furthermore, we describe our preliminary complexation
studies between the TTF-cage 4 and 1,3,5-trinitrobenzene,
which have been carried out in solution using 1H NMR and
UV-vis spectroscopies.
The TTF-cage 4 was designed to participate in host-guest
chemistry,11 and a Cory-Pauling-Koltun (CPK) modeling
suggests that our target, tris-TTF-cage 4, has a rather larger
and more flexible cavity that those of 1 and 3 thereby
increasing the likelihood for 4 to act as a host molecule for
electron-deficient guests such as 1,3,5-trinitrobenzene.12
Retrosynthetic analyses of the TTF-cage 4 reveal a range of
possible disconnections for this novel class of TTF-cage
molecules. The approach that was eventually adopted allows
the rim-spacers to be identically or varied individually, thus
allowing functional groups, e.g., hydrogen-donor/acceptor or
flexible/rigid, long/short, or other types of spacers, to be
incorporated into the cage. The number of TTF moieties can
also easily be changed from three to four, five, etc.
Furthermore, it is possible to change the size and geometry
of the top-spacer in the final step. The flexibility in design
and straightforward synthesis of this novel class of TTF-
cage molecules make them useful for studying their com-
plexation properties with appropriate guest molecules. In the
TTF-cage 4 presented in this Letter triethyleneglycol units
were chosen as the rim-spacers and 1,3,5-trimethylbenzene
as the top-spacer to balance out flexibility and rigidity.
The TTF cage 4 was synthesized as illustrated in Schemes
1 and 2. A THF solution of the cyanoethyl-protected
monopyrrolo-TTF building block9 2 was treated with 1.0
equiv of CsOH‚H2O. This procedure generated the TTF-
monothiolate, which was alkylated with 1.0 equiv of 2-[2-
(2-iodoethoxy)ethoxy]ethanol (5). Subsequently, deprotection/
alkylation with 1.0 equiv of CsOH‚H2O and 1.0 equiv of 5,
respectively, gave (Scheme 1) the TTF derivative 6 in 88%
yield. Mesylation (96%) of 6 in CH2Cl2 followed by
treatment of 7 with NaI in Me2CO gave (86%) the TTF
Figure 1.
and switches.4e,g In addition, TTF has also been used for the
preparation of macrocyclic compounds, such as TTF-belts,5
crisscross TTF-phanes,6 and TTF-cages.7 Conventional cyclo-
phanes1,2 are a fundamentally important class of synthetic
host moleculessthus, it is of interest to develop simple routes
to TTF cyclophanes, which can act as hosts for electron-
deficient guest molecules. Until now, and essentially for
synthetic reasons, the TTF unit has mainly been introduced
into macrocyclic systems as a tetrathio-TTF moiety.3-7 Since
the TTF core has a D2h symmetry with four identical potential
attachment sites, incorporation of the tetrathio-TTF moiety
into macrocyclic systems often results in the isolation of cis/
trans isomeric mixtures, as in the case of the TTF-cage7b
(Figure 1). This inherent cis/trans isomerism may alter the
complexing ability of the host.8 This problem can be
circumvented using the monopyrrolo-TTF building block9
1
(5) For TTF-belts, see: (a) Adam, M.; Enkelmann, V.; Ra¨der, H.-J.;
Ro¨hrich, J.; Mu¨llen, K. Angew. Chem., Int. Ed. Engl. 1992, 31, 309-310.
(b) Matsuo, K.; Takimiya, K.; Aso. Y.; Otsubo, T.; Ogura, F. Chem. Lett.
1995, 523-524. (c) Otsubo, T.; Aso, Y.; Takimiya, K. AdV. Mater. 1996,
8, 203-211. (d) Simonsen, K. B.; Svenstrup, N.; Lau, J.; Thorup, N.; Becher,
J. Angew. Chem., Int. Ed. 1999, 38, 1417-1420. (e) Spanggaard, H.; Prehn,
J.; Nielsen, M. B.; Levillain, E.; Allain, M.; Becher, J. J. Am. Chem. Soc.
2000, 122, 9486-9494. (f) Nielsen, K.; Jeppesen, J. O.; Thorup, N.; Becher,
J. Org. Lett. 2002, 4, 1327-1330.
(6) For crisscross-TTF molecules, see: (a) Tanabe, J.; Kudo, T.;
Okamoto, M.; Kawada, Y.; Ono, G.; Izuoka, A.; Sugawara, T. Chem. Lett.
1995, 579-580. (b) Takimiya, K.; Shibata, Y.; Imamura, K.; Kashihara,
A.; Aso, Y.; Otsubo, T.; Ogura, F. Tetrahedron Lett. 1995, 36, 5045-
5048. (c) Tanabe, J.; Ono, G.; Izuoka, A.; Sugawara, T.; Kudo, T.; Saito,
T.; Okamoto, M.; Kawada, Y. Mol. Cryst. Liq. Cryst. 1997, 296, 61-76.
(d) Takimiya, K.; Imamura, K.; Shibata, Y.; Aso, Y.; Ogura, F.; Otsubo,
T. J. Org. Chem. 1997, 62, 5567-5574. (e) Nielsen, M. B.; Thorup, N.;
Becher, J. J. Chem. Soc., Perkin Trans. 1 1998, 1305-1308. (f) Jeppesen,
J. O.; Takimiya, K.; Becher, J. Org. Lett. 2000, 2, 2471-2473. (g) Takimiya,
K.; Thorup, N.; Becher, J. Chem. Eur. J. 2000, 6, 1947-1954.
(9) (a) Jeppesen, J. O.; Takimiya, K.; Jensen, F.; Becher, J. Org. Lett.
1999, 1, 1291-1294. (b) Jeppesen, J. O.; Takimiya, K.; Jensen, F.; Brimert,
T.; Nielsen, K.; Thorup, N.; Becher, J. J. Org. Chem. 2000, 65, 5794-
5805.
(10) A solid-state X-ray crystal structure analysis of the charge transfer
(CT) complex 3‚TCNQ revealed that TCNQ is associated outside (alongside)
one of two TTF donors, see ref 5f.
(11) Lehn, J.-M. Supramolecular Chemistry; VCH: Weinheim, Germany,
1995.
(12) In contrast to previous synthesized TTF-cage structures, 4 has the
π-electrons from the TTF-moieties pointing into the cavity and thereby
increasing the possibility for complexation with electron-deficient guests.
(7) For TTF-cages, see: (a) Blanchard, P.; Svenstrup, N.; Becher, J.
Chem. Commun. 1996, 615-616. (b) Blanchard, P.; Svenstrup, N.; Rault-
Berthelot, J.; Riou, A.; Becher, J. Eur. J. Org. Chem. 1998, 1743-1757.
(8) For instance, it has been shown that only the cis-isomer of a TTF-
crown is able to complex cations, see ref 4c.
4190
Org. Lett., Vol. 4, No. 24, 2002

Scheme 1. Synthesis of the TTF Derivative 8, Starting from
the Monopyrrolo-TTF Building Block 2
Figure 2. Structure of the model compound 13.
A comparison of the 1H NMR spectra (CDCl3, 298 K) of
the flexible macrocycle 11, the model compound15 13 (Figure
2), and the more rigid TTF-cage 4 revealed (Table 1)
1
Table 1. Selected H NMR Spectroscopic Data (δ Values in
ppm) for 4, 11, and 13 in CDCl3 at 298 K
compd
SCH2
pyrrole-H
Ar-H
derivative 8. The TTF derivative 9 (Scheme 2) was prepared
according to the literature procedure.5f Macrocyclization of
the 36-member-ring system 10 was performed using high-
dilution conditions. A THF solution of 9 was treated with
2.0 equiv of CsOH‚H2O. This procedure generated the TTF-
bisthiolate, which was transferred to a syringe. TTF 8 was
at the same time dissolved in THF and transferred to a second
syringe. By employing a perfuser pump the two solutions
were simultaneously pumped to a reaction flask over a period
of 6 h, affording (Scheme 2) the trisTTF-macrocycle 10 in
extraordinary 81% yield. Removal of the tosyl protecting
groups was carried out in 88% yield by refluxing 10 in a
1:1 mixture of THF-MeOH in the presence of an excess of
NaOMe. Finally, the TTF-cage13 4 was obtained in 45% yield
following N-alkylation of the three pyrrole units in 1114 with
1,3,5-tris(bromomethyl)benzene (12) in DMF containing
NaH.
4
11
13
2.87-2.94 and 3.01-3.10
6.40
6.61
6.43
7.21
3.00
6.75
significant changes in the chemical shift values. For the signal
associated with the six pyrrole protons an upfield shift (∆δ
) 0.21 ppm) was observed between 4 and 11. The signals
associated with the twelve SCH2 protons in 4 split up into
two multiplets each integrating to six protonsspresumably
six of the SCH2 protons are pointing into the cage and six
out of the cage. In addition, a downfield shift (∆δ ) 0.46
ppm) was observed for the three aromatic protons, when
comparing the 1H NMR spectra of the flexible model
compound 13 and the rigid cage 4. These findings clearly
indicate that a closure of the flexible macrocycle 11 to the
somewhat more rigid TTF-cage 4 has taken place.
The redox behavior of the TTF-cage 4 was investigated
in solution by cyclic voltammetry (CV). The CV16 of 4,
performed at 100 mV s-1 at semi-infinite diffusion conditions
in THF (Figure 3), exhibits two oxidation waves correspond-
Scheme 2. Synthesis of the TTF-Cage 4
(13) Data for TTF-cage 4: 1H NMR (300 MHz, CDCl3, 298 K) δ 2.87-
2.94 (m, 6H), 3.01-3.10 (m, 6H), 3.63 (s, 12H), 3.63-3.67 (m, 12H), 4.86
(s, 6H), 6.40 (s, 6H), 7.21 (s, 3H); 13C NMR (75 MHz, CDCl3, 298 K) δ
35.1, 54.4, 70.1, 70.4, 109.8, 112.1, 120.1, 121.5, 127.6, 129.0, 138.3; MS-
(FAB) m/z 1377 (M+, 88), 1378 (M+ + 1, 75), 1379 (M+ + 2, 100); 1380
(M+ + 3, 66), 1381 (M+ + 4, 53); mp 153-153.5 °C. Anal. Calcd for
C51H51N3O6S18‚0.75CH2Cl2 (1379.2): C, 43.08; H, 3.67; N, 2.91. Found:
C, 42.98; H, 3.75; N, 2.79.
(14) Data for macrocycle 11: 1H NMR (300 MHz, CDCl3, 298 K) δ
3.00 (t, J ) 6.2 Hz, 12H), 3.62 (s, 12H), 3.67 (t, J ) 6.2 Hz, 12H), 6.61
(d, J ) 2.0 Hz, 6H); 13C NMR (75 MHz, CDCl3, 298 K) δ 35.0, 69.2,
69.6, 107.3, 110.6, 117.0, 121.6, 126.8; MS(FAB) m/z 1263 (M+, 98), 1264
(M+ + 1, 72), 1265 (M+ + 2, 100), 1266 (M+ + 3, 59), 1267 (M+ + 4,
46); mp 118-120 °C. Anal. Calcd for C42H45N3O6S18 (1264.9): C, 39.88;
H, 3.59; N, 3.32. Found: C, 40.21; H, 3.32; N, 3.34.
(15) Data for 13: 1H NMR (300 MHz, CDCl3, 298 K) δ 2.43 (s, 18H),
4.91 (s, 6H), 6.43 (s, 6H), 6.75 (s, 3H); 13C NMR (75 MHz, CDCl3, 298
K) δ 19.2, 53.8, 112.8, 112.9, 119.9, 124.9, 127.2, 139.0, one carbon is
missing; MS(FAB) m/z 1119 (M+); mp 220-220.5 °C.
(16) CV was performed using a 0.43 mM solution of 4 in anhydrous
THF with n-Bu4NPF6 (0.40 M) as supporting electrolyte and Ag/AgCl as
reference electrode. Electrochemical experiments were carried out in a
glovebox containing dry, oxygen-free (<1 vpm) argon, at room temperature.
The number of electron processes were calculated by using dichloronaph-
thoquinon as internal reference.
Org. Lett., Vol. 4, No. 24, 2002
4191

Figure 4. Crystal structure of the TTF-cage 4‚3CDCl3. Hydrogen
atoms are omitted for clarity.
× 10-4 M) resulted in an immediate color change from
orange to light green and the appearance of a weak CT
absorption band, centered on λmax 646 nm, indicating that a
complexation between host and guest is taking place. The
1H NMR spectrum19 (250 MHz) recorded on a 1:1 mixture
of 4 and 1,3,5-trinitrobenzene at 298 K in CDCl3 revealed
weak upfield shifts for the resonances associated with the
three aromatic protons (∆δ ) 0.09 ppm) on the 1,3,5-
trinitrobenzene unit and the six pyrrole protons (∆δ ) 0.05
ppm) on 4, respectively. Downfield shifts were observed for
the three aromatic protons (∆δ ) 0.10 ppm) on 4 and for
one of the SCH2 multiplets20 (2.87 - 2.94 ppm, ∆δ ) 0.03
ppm), respectively. The fact that only one of the SCH2
multiplets is downfield shifted might indicate that 1,3,5-
trinitrobenzene is complexed inside the cage.
In summary, an efficient and flexible synthetic strategy
for the preparation of TTF-cages has been developed. From
1H NMR and UV-vis spectroscopies it was shown that
complexation between the TTF-cage 4 (host) and 1,3,5-
trinitrobenzene (guest) took place in solution. However, these
results do not provide any solid information regarding
whether the complexation is taking place inside or outside
the cavity of the host molecule 4. To answer this question a
solid-state structure determination of the complex is required.
The synthetic strategy described allows us to make related
TTF-cages in which the rim- and top-spacersstogether with
the number of TTF moietiesscan be varied to fine-tune the
complexation properties of the host with 1,3,5-trinitrobenzene
or other guests.
Figure 3. Cyclic voltammogram of 4 recorded in THF.
ing to the generation of the radical cation (TTF•+) and the
dication (TTF2+) respectively at ∼0.48 and ∼0.85 V vs Ag/
AgCl. At 100 mV s-1, the first wave is a classical reversible
process. A weak broadening of this oxidation wave is
observed. However, it is not significant enough to make any
conclusion whether intra- or intermolecular interactions are
taking place between the TTF moieties. The second wave
reveals that a strong adsorption to the electrode is taking
place, probably due to the insolubility of the dication in THF.
Thin layer cyclic voltammetry (TLCV) showed that the first
oxidation wave corresponds to three one-electron processes.
The second wave is probably a similar process but the
adsorption phenomenon observed does not allow any un-
equivocal conclusion to be made.
Single crystals of 4 suitable for X-ray diffraction analysis
were obtained by crystallization17 from CDCl3 and the
molecular structure of 4 is illustrated in Figure 4. The unit
cell contains two TTF-cage molecules and six CDCl3
molecules, three per TTF-cage. Two of the CDCl3 molecules
reside inside the cavity of 4, while the other is positioned
outside the cage. None of the CDCl3 molecules appears to
be involved in any strong interactions with the TTF-cage.
Somewhat surprisingly, no intra- or intermolecular staking
between the TTF moieties was observed, and only one shorter
nonbonding S‚‚‚S distance was observed. The fact that no
intramolecular stacking is observed and that two CDCl3
molecules reside inside the cavity of the solid-state structure
of 4 give some promise that 4 may act as a host molecule
for other guest molecules as well.
Acknowledgment. We thank the University of Southern
Denmark for a Ph.D. Scholarship to K.A.N. and Carlsberg-
fondet for financial support to J.O.J.
Supporting Information Available: Crystallographic
data for 4. This material is available free of charge via the
Internet at http://pubs.acs.org.
Preliminary complexation studies were carried out for 1:1
solutions18 of the TTF-cage 4 (host) and 1,3,5-trinitrobenzene
(guest) using UV-vis and 1H NMR spectroscopies. Addition
of 1.0 equiv of 1,3,5-trinitrobenzene to a solution of 4 (5.0
OL026816H
(17) Crystals of 4 utilized in the X-ray analysis crystallized out from a
CDCl3 solution of 4 used for NMR spectroscopy.
(18) A CPK model inspection revealed that only one 1,3,5-trinitrobenzene
(guest) can be accommodated inside the cage (host).
(19) No line broadening indicating the radical character of the cage was
observed.
(20) The resonance associated with the other SCH2 multiplet (3.01-
3.10 ppm) did not reveal any shift upon complexation.
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Org. Lett., Vol. 4, No. 24, 2002