- Email: [email protected]
Upper rim tetrathiafulvalene-bridged calix[4]arenes
Tetrahedron Letters 52 (2011) 2881–2884
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Upper rim tetrathiafulvalene-bridged calix[4]arenes Matthias H. Düker a, Rafael Gómez b, Christophe M. L. Vande Velde c, Vladimir A. Azov a,⇑ a b c
University of Bremen, Department of Chemistry, Leobener Str. NW 2C, D-28359 Bremen, Germany Universidad Complutense, Departamento de Química Orgánica, Avda. Complutense s/n, E-28040 Madrid, Spain Karel de Grote University College, Department of Applied Engineering, Salesianenlaan 30, 2660 Antwerp, Belgium
a r t i c l e
i n f o
Article history: Received 17 February 2011 Revised 22 March 2011 Accepted 28 March 2011 Available online 5 April 2011 Keywords: Calixarenes Tetrathiafulvalenes Cyclic voltammetry Molecular recognition Weak hydrogen bonds
a b s t r a c t The synthesis of novel upper rim calix[4]arene–tetrathiafulvalene conjugates 1a–d has been performed by bridging the tetrachloromethylated calix[4]arene derivative 4 with the corresponding tetrathiafulvalene-dithiolates. The cyclic voltammetry of 1a–d shows a two-step oxidation behavior, whereas NMR binding titrations showed their binding affinity to pyridinium salts. X-ray structure of 4 features calixarene fixed in the pinched cone conformation; its crystal packing is defined by the network of C–HCl weak hydrogen bonds. Ó 2011 Elsevier Ltd. All rights reserved.
Tetrathiafulvalenes1 have an established history of application in various areas of chemistry and materials science. Initially, these electron-rich heterocyclic compounds found extensive use in molecular electronics.2 In later years, due to their unique electronic properties, they have been widely employed as building blocks in diverse supramolecular systems, where they have played the role of redox switching units3 in a variety of architectures,4 among which interlocked supramolecular devices5 are one of the most fascinating. Calixarenes,6 a family of macrocyclic compounds, have been shown to be superb molecular scaffolds for the construction of macromolecular and supramolecular architectures.7 Being interested in host–guest chemistry and in the design of redox-responsive assemblies based on the tetrathiafulvalenes,8 we have turned our attention to the excellent scaffolding features of the calix[4]arene moiety. Calix[4]arenes, the smallest members of the family, have a bowl shape in the cone conformation with a cavity suitable for encapsulation of guest molecules. Until now, only relatively few tetrathiafulvalene–calix[4]arene derivatives have been reported,9,10 and almost all of them were lower rim conjugates.10 Some of these compounds displayed sensing properties toward cationic and anionic species.10b–e,g Additionally, 1,3-alternate thiacalix[4]arene– TTFs,11 as well as calix[4]pyrrolo-TTFs12 and TTF-bridged resorcin[4]arene cavitands,13 which possess structurally-related architectures, are worth mentioning.
⇑ Corresponding author. Tel.: +49 421 218 63126; fax: +49 421 218 63120. E-mail address: [email protected] (V.A. Azov). 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.03.140
Thus, we decided to extend the bowl of calix[4]arenes by the attachment of the two tetrathiafulvalene bridges14 to its upper rim (compound 1, Scheme 1). Molecular modeling15 using semiempirical methods has shown that such structures should have a rather broad conformational space. Several low-lying conformations with comparable energies within a rather narrow energy range could be determined. In a set of ‘closed’ conformations, two tetrathiafulvalene units are extending above the calix[4]arene bowl and are being tilted into the cavity; the degree of tilt can vary, together with the deformation of the calixarene bowl (cone— pinched cone conformations). In ‘open’ conformations, the two TTF moieties are far away from each other pointing outside the cavity. Closed conformations possess an empty cavity suitable for guest encapsulation. We expected that the presence of electronrich TTF moieties may contribute to the binding of electrondeficient guests. In addition, redox-active TTF moieties offer the potential of sensing through electrochemical methods and switching of the receptor’s binding ability by oxidation/reduction. Herein, we present the synthesis, electrochemical, and binding properties of four novel upper rim calix[4]arene–tetrathiafulvalene electroactive conjugates. The calixarene backbone was prepared from commercially available 4-tert-butylcalix[4]arene 2. First, the tert-butyl groups in compound 2 were removed in a ‘retro-Friedel–Crafts’ reaction and the four hydroxyl groups were propylated in a Williamson etherification reaction, using NaH as the base, to afford calix[4]arene 3 fixed in the cone conformation (Scheme 1). Then, 3 was chloromethylated using paraformaldehyde/HCl in dioxane/H3PO4/AcOH to afford the key functionalized intermediate 4.14b Calix[4]arene–tetrathiafulvalene
2882
M. H. Düker et al. / Tetrahedron Letters 52 (2011) 2881–2884
Figure 1. Side view of 4 displaying the pinched cone conformation of the calix[4]arene bowl. Only the major orientation of the disordered propyl chains is shown. Thermal ellipsoids are shown with 50% probability. Hydrogen atoms are omitted. For atom numbering, crystal packing and tables of short contacts, see Supplementary data.
Scheme 1. Synthesis of calix[4]arene–tetrathiafulvalene conjugates 1a–d.
conjugates 1a–d16 were prepared by reaction of TTF dithiolates,17 generated in situ from 2,3-bis(2-cyanoethylthio)tetrathiafulvalenes 5a–d, with the calixarene derivative 4.18 The products precipitated from the reaction mixtures upon methanol addition and could be separated from remaining traces of polar substances using flash chromatography, affording pure materials as bright orange–yellow solids in 59–64% yields. Such yields are quite remarkable, taking into account that two relatively strained macrocycles are formed in a double macrocyclization. The new upper rim TTF–calix[4]arene conjugates displayed high solubility in relatively non-polar organic solvents such as chloroform. Among compounds 1a–d only 1b could be crystallized, unfortunately yielding only very small multiply-twinned crystals, found to be unsuitable for characterization by X-ray crystallography. On the other hand, chloromethylated derivative 4 readily afforded large transparent crystals upon slow evaporation of a heptane/chloroform solution. Compound 4 crystallizes in the space group P21/c, without intramolecular symmetry (Z0 = 1).19,20 It adopts a pinched cone conformation (Fig. 1): one pair of opposite phenolic rings is almost parallel to each other, being pinched into the cavity with an interplanar angle of 7.95(6)°, whereas the second pair is widely open with an angle of 75.79(7)°. In the crystal, the calixarenes form loosely packed columns in which the bowls are stacked in the a direction. Side chains from neighboring molecules penetrate into the columns, mainly through the formation of non-classical weak hydrogen bonds21 in the direction of the pitched-out phenolic rings. Two chlorine atoms, located on the pitched-out phenolic rings, serve as 2-fold hydrogen bond acceptors. Two weak H-bonds involving hydrogens of chloromethylene groups are particularly short (2.65 and 2.75 Å). In the direction perpendicular to these interactions, where the calixarene rings are parallel to each other, there are CH–p interactions over an inversion center, connecting chloromethyl protons to the centroid of one of the benzene rings (2.93 Å). The UV/vis spectra of 1a–d (CH2Cl2, 293 K) showed the typical absorption pattern for tetrathio-substituted TTF derivatives with absorption bands at kmax ca. 310 and 330 nm, as well as a shoulder at ca. 390 nm.
As expected for calix[4]arenes in the cone conformation, 1H NMR spectra.13 presented two sets of the AB splitting patterns for the bridging diastereotopic methylene protons (ArCHaHbAr) of the calixarene bowl, with two pairs of doublets (2J = 13 Hz) belonging to two different types of CH2 bridges, lying either below or to the side of TTF groups (Fig. 2). The SCH2Ar protons of the TTF bridges also displayed the AB splitting patterns for the diastereotopic methylene protons (ArCHcHdS), with one pair of doublets (2J = 15.2 Hz), being an indication for the averaged C2v symmetry of the molecules. Furthermore, the signals of the aromatic protons of the calixarene bowl (He and Hf), especially those lying below the TTF bridges, were significantly broadened. Variable temperature NMR measurements with 1a and b were performed to give an insight into their conformational behavior.15 At lower temperatures, NMR spectra showed the splitting of the two aromatic signals into a pair of doublets, the strong broadening of one asymmetric proton belonging to ArCH2S bridges (Hd), the broadening and splitting of the signals, belonging to propyl chains,
Figure 2. VT-NMR of 1a. Signal indicated with (⁄) belong to residual CHDCl2.
M. H. Düker et al. / Tetrahedron Letters 52 (2011) 2881–2884
in pairs of broadened multiplets, as well as the splitting of the triplets, belonging to SCH2 groups (Hg), into two broad multiplets (Fig. 2). These spectroscopic data serve as an indication of desymmetrization of the calix[4]arene bowl into two degenerated pinched cone conformations and slowing down of the conformational interconversion between them at low temperatures. The splitting of the Hg triplets into two broad multiplets implies that two methylene groups become nonequivalent, which is likely to arise upon interaction of two closely spaced TTF moieties within an asymmetric closed conformation, such as the pinched cone. Thus, we could assume that the closed conformation should be the preferred one in solution, although intermolecular processes, such as dimerization of two molecules at lower temperatures, cannot be entirely ruled out. The electrochemical properties of calixarene–TTF conjugates 1a–d were investigated by cyclic voltammetry (CV) in dichloromethane/Bu4N+ ClO4 solutions (Fig. 3). Compounds 1a–d displayed the classical electrochemical behavior of tetrathiafulvalene derivatives, showing two quasi-reversible electrochemical processes on the cathodic scan, the first one at E1=2 1 = 0.30– 0.33 V (vs Ag/AgCl, Table 1) leading to the TTF radical cation, and the second one at E1=2 2 = 0.61–0.71 V, giving the dication. In contrast with the CVs of several other bis-tetrathiafulvalene derivatives,8,10d,22 the first oxidation wave did not display splitting, indicating that both TTF moieties are oxidized at the same potential and are not in electronic communication with each other in this type of compounds. Probably, the TTF–TTF interaction is disabled by the long distance between the two TTF moieties. Moreover, the cyclic voltammograms of compounds 1a–d showed additional oxidation waves at around 1.40 and 1.80 V, most likely arising from the oxidation of the calixarene cores. Calix[4]arenes are known to bind different electron-deficient guests inside their bowls,23,24 especially soft organic cations, by p–cation interactions. Molecular modeling has shown that quater-
2883
Figure 4. Structures of guests 6 and 7.
nary pyridinium salts can tightly fit inside the binding cavity formed by the calixarene and the TTF-molecular tweezers (Fig. 4). Binding studies25 were performed by NMR binding titrations in chloroform using compound 1b as a host and Nmethylpyridinium iodide (NMPI) 6 and 1-methyl-4-(methoxycarbonyl)pyridinium iodide 7 as guests.15 As expected, NMR spectra showed fast host–guest exchange and upfield shift of the guest resonances due to shielding effects of the benzene rings. Both guests 6 and 7 showed relatively weak binding with Ka = 7 ± 1 and 20 ± 2 m1, respectively. The parent calix[4]arene 3 displays only slightly lower binding efficiency with NMPI with Ka = 6.4 m1,23c,d implying that, in the case of receptors 1, binding is also mostly due to the p–cation interactions involving the calixarene bowl. This conclusion is supported by UV/vis spectra of the host/guest mixtures, which did not show the presence of any additional bands which could be contributed to charge-transfer interactions between host and guest molecules. The 4-fold alkyl substitution of the lower rim of 1a–d leads to the deformation of the calixarene bowl to the pinched cone conformation and is unfavorable for guest binding. Thus, the use of modified architectures with only two alkoxy substituents or two bridges on the lower rim connecting the neighboring hydroxyl groups is likely to increase the rigidity of the calix[4]arene bowl and improve the binding strength of the receptors, as it was shown before.24 Furthermore, pyrrolo-tetrathiafulvalenes,26 which are known for their better electron-donating and binding26c properties than thioalkyl-substituted TTFs, will be also tried as arms aiming to increase the binding efficiency. In summary, the first upper rim calixarene conjugates with upper rim tetrathiafulvalene bridges have been prepared and characterized using various physical methods. Calixarene–TTF conjugates showed moderate binding with pyridinium cations in solution. The synthesis of the modified upper rim TTF–calixarene conjugates both in cone and 1,3-alternate conformations of the calixarene bowl is currently in progress. Acknowledgments M.D. is grateful to BFK NaWi, University of Bremen, for financial support. We are thankful to Dr. T. Dülcks and Ms. D. Kemken (MS) and Mr. J. Stelten (NMR) for their help with the characterization of the new compounds. We are grateful to Matthias Zeller (STaRBURSTT Cyberinstrumentation Consortium, Youngstown State University, OH, USA) for collecting the X-ray data.
Figure 3. Cyclic voltammogram of TTF–calixarene conjugate 1a (CH2Cl2/0.1 m Bu4NClO4, scan rate 200 mV s1).
Supplementary data
Table 1 Electrochemical data of calixarene–TTF derivatives 1a
Supplementary data (all experimental procedures, 1D and 2D NMR spectra, NMR signal assignment, full VT-NMR spectra, details on molecular modeling, CV, crystallography, and binding studies) associated with this article can be found, in the online version, at doi:10.1016/j.tetlet.2011.03.140.
a
Compound
E1=2 ox1 (V)
E1=2 ox2 (V)
Eox3 (V)
1a 1b 1c 1d
0.30 0.33 0.31 0.33
0.66 0.61 0.61 0.71
1.40 (onset), 1.76 1.40 (onset), 1.82 1.45 (peak), 1.80 1.82
Data were obtained using a one-compartment cell in CH2Cl2/0.1 m Bu4NClO4, Pt as the working and counter electrodes. Values given at room temperature versus Ag/Ag+, scan rate 200 mV/s.
References and notes 1. For reviews and monographs on tetrathiafulvalenes, see: (a) Krief, A. Tetrahedron 1986, 42, 1209–1252; (b) Segura, J. L.; Martín, N. Angew. Chem., Int. Ed. 2001, 40, 1372–1409; (c) Fabre, J. M. Chem. Rev. 2004, 104, 5133–5150; Yamada, J.; Sugimoto, T. TTF Chemistry. Fundamentals and Applications of Tetrathiafulvalene; Springer: Heidelberg, 2004.
2884
M. H. Düker et al. / Tetrahedron Letters 52 (2011) 2881–2884
2. (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, D. F. Chem. Rev. 2004, 104, 4891–4945. 3. Canevet, D.; Sallé, M.; Zhang, G.; Zhang, D.; Zhu, D. Chem. Commun. 2009, 2245– 2269. 4. (a) Bryce, M. R.; Devonport, W.; Goldberg, 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. 5. (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. N. P.; Flood, A. H.; Fernández, J. M.; Stoddart, J. F. Top. Curr. Chem. 2005, 262, 99–132. 6. For comprehensive reviews and monographs on calixarenes, see: (a) Böhmer, V. Angew. Chem., Int. Ed. Engl. 1995, 34, 713–745; (b) Asfari, Z.; Böhmer, V.; Harrowfield, J.; Vicens, J. Calixarenes 2001; Kluwer Academic Publishers: Dordrecht, 2001; (c) Gutsche, C. D. Calixarenes. An Introduction, 2nd ed.; RSC: Cambridge, 2008. 7. For reviews on application of calixarenes, see: (a) Ikeda, A.; Shinkai, S. Chem. Rev. 1997, 97, 1713–1734; (b) Casnati, A.; Sansone, F.; Ungaro, R. Acc. Chem. Res. 2003, 36, 246–254; (c) Baldini, L.; Casnati, A.; Sansone, F.; Ungaro, R. Chem. Soc. Rev. 2007, 36, 254–266; (d) Lhoták, P. Top. Curr. Chem. 2005, 255, 65–95; (e) Rebek, J., Jr. Chem. Commun. 2000, 637–643; (f) Bogdan, A.; Rudzevich, Y.; Vysotsky, M. O.; Böhmer, V. Chem. Commun. 2006, 2941–2952; (g) Sansone, F.; Baldini, L.; Casnati, A.; Ungaro, R. New J. Chem. 2010, 34, 2715–2728. 8. (a) Azov, V. A.; Gómez, R.; Stelten, J. Tetrahedron 2008, 64, 1909–1917; (b) Skibin´ski, M.; Gómez, R.; Lork, E.; Azov, V. A. Tetrahedron 2009, 65, 10348– 10354. 9. (a) Regnouf-de-Vains, J.-B.; Sallé, M.; Lamartine, R. J. Chem. Soc., Perkin Trans 2 1997, 2461–2462; (b) Lee, M. H.; Cao, Q.-Y.; Kim, S. K.; Sessler, J. L.; Kim, J. S. J. Org. Chem. 2011, 76, 870–874. 10. (a) Zhao, B.-T.; Blesa, M.-J.; Mercier, N.; Le Derf, F.; Sallé, M. J. Org. Chem. 2005, 70, 6254–6257; (b) Zhao, B.-T.; Blesa, M.-J.; Mercier, N.; Le Derf, F.; Sallé, M. New J. Chem. 2005, 1164–1167; (c) Blesa, M.-J.; Zhao, B.-T.; Allain, M.; Le Derf, F.; Sallé, M. Chem. Eur. J. 2006, 12, 1906–1914; (d) Lyskawa, J.; Sallé, M.; Balandier, J.-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) Zhao, B.-T.; Chen, J.-Q.; Qu, G.-R. Chinese J. Org. Chem. 2007, 27, 1424–1427; (g) Lyskawa, J.; Canevet, D.; Allain, M.; Salle, M. Tetrahedron Lett. 2010, 51, 5868–5872. 11. (a) Zhao, B.-T.; Zhou, Z.; Yan, Z.-N.; Belhadj, E.; Le Derf, F.; Salle, M. Tetrahedron Lett. 2010, 51, 5815–5818; (b) Zhao, B.-T.; Guo, W.-B.; Hu, P.-Z. Heterocycles 2010, 81, 1661–1667. 12. (a) Nielsen, K. A.; Cho, W.-S.; Lyskawa, J.; Levillain, E.; Lynch, V. M.; Sessler, J. L.; Jeppesen, J. O. J. Am. Chem. Soc. 2006, 128, 2444–2451; (b) Nielsen, K. A.; Sarova, G. H.; Martín-Gomis, L.; Fernández-Lázaro, F.; Stein, P. C.; Sanguinet, L.; Levillain, E.; Sessler, J. L.; Guldi, D. M.; Sastre-Santos, Á.; Jeppesen, J. O. J. Am. Chem. Soc. 2008, 130, 460–462; (c) Nielsen, K. A.; Martín-Gomis, L.; Sarova, G. H.; Sanguinet, L.; Gross, D. E.; Fernández-Lázaro, F.; Stein, P. C.; Levillain, E.; Sessler, J. L.; Guldi, D. M.; Sastre-Santos, Á.; Jeppesen, J. O. Tetrahedron 2008, 64, 8449–8463; (d) Park, J. S.; Le Derf, F.; Bejger, C. M.; Lynch, V. M.; Sessler, J. L.; Nielsen, K. A.; Johnsen, C.; Jeppesen, J. O. Chem. Eur. J. 2010, 16, 848–854. 13. Frei, M.; Diederich, F.; Tremont, R.; Rodriguez, T.; Echegoyen, L. Helv. Chim. Acta 2006, 89, 2040–2057. 14. Only a few calix[4]arenes with rigid upper bridges have been reported: (a) Ikeda, A.; Shinkai, S. J. Chem. Soc., Perkin Trans 1 1993, 2671–2673; (b) Ikeda, A.; Yoshimura, M.; Lhotak, P.; Shinkai, S. J. Chem. Soc., Perkin Trans 1 1996, 1945– 1950. 15. See Supplementary data for additional details. 16. Characterization data of compound 1a: orange–yellow powder (59%); mp: 145– 150°C; Rf = 0.76 (CH2Cl2/PE, 1:1); 1H NMR (360 MHz, CDCl3): d = 0.88 (t, 3 J = 6.8 Hz, 12H), 1.02 (t, 3J = 7.6 Hz, 12H), 1.23–1.31 (m, 16H), 1.35–1.44 (m, 8H), 1.58–1.67 (m, 8H), 1.88–2.01 (m, 8H), 2.82 (t, 3J = 7.4 Hz, 8H), 3.01 (d, 2 J = 13.0 Hz 2H), 3.15 (d, 2J = 13.0 Hz, 2H), 3.55 (d, 2J = 15.2 Hz, 4H), 3.78 (t, 3 J = 7.2 Hz, 8H), 4.14 (d, 2J = 15.2 Hz, 4H), 4.30 (d, 2J = 13.0 Hz, 2H), 4.37 (d,
2
17.
18.
19. 20.
21. 22.
23.
24.
25. 26.
J = 13.0 Hz, 2H), 6.56 (br s, 4H), 6.79 (br s, 4H); 13C NMR (90 MHz, CDCl3): d = 10.4, 14.0, 22.5, 23.4, 28.2, 29.7, 29.8, 30.2, 31.3, 36.2, 39.3, 77.1, 108.5, 111.3, 127.6, 128.0, 128.2, 133.2, 134.3, 135.4, 155.2; UV–vis (CH2Cl2): kmax = 311 (36400), 333 (33000), 386 sh (11400 dm3 mol1 cm1) nm; MS (ESI+): m/z (%) 1640 (M+, 40), 1663 ([M+Na]+, 100), 1679 ([M+K]+, 80); HR-MS (MALDI, matrix: DCTB): m/z calcd for C80H104O4S16 (M+) 1640.3461, found 1640.3704. (a) Simonsen, K. B.; Svenstrup, N.; Lau, J.; Simonsen, O.; Mørk, P.; Kristensen, G. J.; Becher, J. Synthesis 1996, 407–418; (b) Svenstrup, N.; Rasmussen, K. M.; Hansen, T. K.; Becher, J. Synthesis 1994, 809–812. General procedure for the synthesis of 1: bis-cyanoethyl TTF derivative 5 (0.22 mmol) was dissolved in dry DMF (10 mL) and degassed by 2–3 freezepump-thaw cycles; then CsOH (0.46 mmol, 0.32 mL) was added as a 1.5 m solution in MeOH at 0 °C. The mixture was allowed to warm to rt and stirred for 30 min, changing its color from orange to dark brown–red. Calixarene 4 (0.1 mmol) was dissolved in dry THF (3 mL), and the solution was degassed by a freeze-pump-thaw cycle. Afterward the calixarene solution was added in one portion to the previously prepared thiolate solution at 20 °C, and then the mixture was allowed to warm to rt gradually. The reaction mixture turned orange–yellow, a yellow precipitate appeared for some derivatives. The reaction was allowed to stir for additional 30 min at rt, and then THF was removed under vacuum. The product was precipitated by addition of MeOH and filtered off. The residue was finally purified by flash chromatography (FC) on silica gel. The structure was solved and refined using SHELX: Sheldrick, G. M. Acta Cryst. 2008, A64, 112–122. Crystallographic data for 4: C44H52Cl4O4, M = 786.66, monoclinic, a = 14.021(2) Å, b = 17.163(3) Å, c = 17.520(3) Å, b = 100.600(2)°, V = 4144.1(12) Å3, T = 100(2) K, space group P21/c, Z = 4, 43438 reflections measured, 12758 independent reflections (Rint = 0.0291). The final R1 values were 0.0437 (I>2r(I)). The final wR(F2) values were 0.1142 (I>2r(I)). The final R1 values were 0.0556 (all data). The final wR(F2) values were 0.1257 (all data). GOF on F2 was 1.032. The data for the structure have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC813254. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, (fax: +44 (0)1223 336033 or email: [email protected]). Desiraju, G. R. Chem. Commun. 2005, 2995–3001; Steiner, T. Angew. Chem., Int. Ed. 2002, 41, 48–76. (a) Jørgensen, M.; Lerstrup, K. A.; Bechgaard, K. J. Org. Chem. 1991, 56, 5684– 5688; (b) Blanchard, P.; Svenstrup, N.; Becher, J. Chem. Commun. 1996, 615– 616; (c) Spanggaard, H.; Prehn, J.; Nielsen, M. B.; Levillain, E.; Allain, M.; Becher, J. J. Am. Chem. Soc. 2000, 122, 9486–9494; (d) Le Derf, F.; Levillain, E.; Trippé, G.; Gorgues, A.; Sallé, M.; Sebastian, R.-M.; Caminade, A.-M.; Majoral, J.-P. Angew. Chem., Int. Ed. 2001, 40, 224–227; (e) Bouguessa, S.; Hervé, K.; Golhen, S.; Ouahab, L.; Fabre, J.-M. New J. Chem. 2003, 27, 560–564. (a) Lhoták, P.; Shinkai, S. J. Phys. Org. Chem. 1997, 105, 273–285; (b) Araki, K.; Shimizu, H.; Shinkai, S. Chem. Lett. 1993, 205–208; (c) Araki, K.; Hayashida, H. Chem. Lett. 2000, 20–21; (d) Araki, K.; Hayashida, H. Tetrahedron Lett. 2000, 41, 1209–1213; (e) Arduini, A.; Pochini, A.; Secchi, A. Eur. J. Org. Chem. 2000, 2325– 2334; (f) Arduini, A.; Giorgi, G.; Pochini, A.; Secchi, A.; Ugozzoli, F. J. Org. Chem. 2001, 66, 8302–8308. (a) Arduini, A.; McGregor, W. M.; Paganuzzi, D.; Pochini, A.; Secchi, A.; Ugozzoli, F.; Ungaro, R. J. Chem. Soc., Perkin Trans 2 1996, 839–846; (b) Arena, G.; Contino, A.; Longo, E.; Spoto, G.; Arduini, A.; Pochini, A.; Secchi, A.; Massera, C.; Ugozzoli, F. New J. Chem. 2004, 28, 56–61; (c) Pescatori, L.; Arduini, A.; Pochini, A.; Secchi, A.; Massera, C.; Ugozzoli, F. Org. Biomol. Chem. 2009, 7, 3698–3708. For a review on determination of binding constants using NMR, see: Fielding, L. Tetrahedron 2000, 56, 6151–6170. (a) Jeppesen, J. O.; Takimiya, K.; Jensen, F.; Brimert, T.; Nielsen, K.; Thorup, N.; Becher, J. J. Org. Chem. 2000, 65, 5794–5805; (b) Jeppesen, J. O.; Becher, J. Eur. J. Org. Chem. 2003, 3245–3266; (c) Nielsen, M. B.; Jeppesen, J. O.; Lau, J.; Lomholt, C.; Damgaard, D.; Jacobsen, J. P.; Becher, J.; Stoddart, J. F. J. Org. Chem. 2001, 66, 3559–3563.
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Upper rim tetrathiafulvalene-bridged calix[4]arenes Matthias H. Düker a, Rafael Gómez b, Christophe M. L. Vande Velde c, Vladimir A. Azov a,⇑ a b c
University of Bremen, Department of Chemistry, Leobener Str. NW 2C, D-28359 Bremen, Germany Universidad Complutense, Departamento de Química Orgánica, Avda. Complutense s/n, E-28040 Madrid, Spain Karel de Grote University College, Department of Applied Engineering, Salesianenlaan 30, 2660 Antwerp, Belgium
a r t i c l e
i n f o
Article history: Received 17 February 2011 Revised 22 March 2011 Accepted 28 March 2011 Available online 5 April 2011 Keywords: Calixarenes Tetrathiafulvalenes Cyclic voltammetry Molecular recognition Weak hydrogen bonds
a b s t r a c t The synthesis of novel upper rim calix[4]arene–tetrathiafulvalene conjugates 1a–d has been performed by bridging the tetrachloromethylated calix[4]arene derivative 4 with the corresponding tetrathiafulvalene-dithiolates. The cyclic voltammetry of 1a–d shows a two-step oxidation behavior, whereas NMR binding titrations showed their binding affinity to pyridinium salts. X-ray structure of 4 features calixarene fixed in the pinched cone conformation; its crystal packing is defined by the network of C–HCl weak hydrogen bonds. Ó 2011 Elsevier Ltd. All rights reserved.
Tetrathiafulvalenes1 have an established history of application in various areas of chemistry and materials science. Initially, these electron-rich heterocyclic compounds found extensive use in molecular electronics.2 In later years, due to their unique electronic properties, they have been widely employed as building blocks in diverse supramolecular systems, where they have played the role of redox switching units3 in a variety of architectures,4 among which interlocked supramolecular devices5 are one of the most fascinating. Calixarenes,6 a family of macrocyclic compounds, have been shown to be superb molecular scaffolds for the construction of macromolecular and supramolecular architectures.7 Being interested in host–guest chemistry and in the design of redox-responsive assemblies based on the tetrathiafulvalenes,8 we have turned our attention to the excellent scaffolding features of the calix[4]arene moiety. Calix[4]arenes, the smallest members of the family, have a bowl shape in the cone conformation with a cavity suitable for encapsulation of guest molecules. Until now, only relatively few tetrathiafulvalene–calix[4]arene derivatives have been reported,9,10 and almost all of them were lower rim conjugates.10 Some of these compounds displayed sensing properties toward cationic and anionic species.10b–e,g Additionally, 1,3-alternate thiacalix[4]arene– TTFs,11 as well as calix[4]pyrrolo-TTFs12 and TTF-bridged resorcin[4]arene cavitands,13 which possess structurally-related architectures, are worth mentioning.
⇑ Corresponding author. Tel.: +49 421 218 63126; fax: +49 421 218 63120. E-mail address: [email protected] (V.A. Azov). 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.03.140
Thus, we decided to extend the bowl of calix[4]arenes by the attachment of the two tetrathiafulvalene bridges14 to its upper rim (compound 1, Scheme 1). Molecular modeling15 using semiempirical methods has shown that such structures should have a rather broad conformational space. Several low-lying conformations with comparable energies within a rather narrow energy range could be determined. In a set of ‘closed’ conformations, two tetrathiafulvalene units are extending above the calix[4]arene bowl and are being tilted into the cavity; the degree of tilt can vary, together with the deformation of the calixarene bowl (cone— pinched cone conformations). In ‘open’ conformations, the two TTF moieties are far away from each other pointing outside the cavity. Closed conformations possess an empty cavity suitable for guest encapsulation. We expected that the presence of electronrich TTF moieties may contribute to the binding of electrondeficient guests. In addition, redox-active TTF moieties offer the potential of sensing through electrochemical methods and switching of the receptor’s binding ability by oxidation/reduction. Herein, we present the synthesis, electrochemical, and binding properties of four novel upper rim calix[4]arene–tetrathiafulvalene electroactive conjugates. The calixarene backbone was prepared from commercially available 4-tert-butylcalix[4]arene 2. First, the tert-butyl groups in compound 2 were removed in a ‘retro-Friedel–Crafts’ reaction and the four hydroxyl groups were propylated in a Williamson etherification reaction, using NaH as the base, to afford calix[4]arene 3 fixed in the cone conformation (Scheme 1). Then, 3 was chloromethylated using paraformaldehyde/HCl in dioxane/H3PO4/AcOH to afford the key functionalized intermediate 4.14b Calix[4]arene–tetrathiafulvalene
2882
M. H. Düker et al. / Tetrahedron Letters 52 (2011) 2881–2884
Figure 1. Side view of 4 displaying the pinched cone conformation of the calix[4]arene bowl. Only the major orientation of the disordered propyl chains is shown. Thermal ellipsoids are shown with 50% probability. Hydrogen atoms are omitted. For atom numbering, crystal packing and tables of short contacts, see Supplementary data.
Scheme 1. Synthesis of calix[4]arene–tetrathiafulvalene conjugates 1a–d.
conjugates 1a–d16 were prepared by reaction of TTF dithiolates,17 generated in situ from 2,3-bis(2-cyanoethylthio)tetrathiafulvalenes 5a–d, with the calixarene derivative 4.18 The products precipitated from the reaction mixtures upon methanol addition and could be separated from remaining traces of polar substances using flash chromatography, affording pure materials as bright orange–yellow solids in 59–64% yields. Such yields are quite remarkable, taking into account that two relatively strained macrocycles are formed in a double macrocyclization. The new upper rim TTF–calix[4]arene conjugates displayed high solubility in relatively non-polar organic solvents such as chloroform. Among compounds 1a–d only 1b could be crystallized, unfortunately yielding only very small multiply-twinned crystals, found to be unsuitable for characterization by X-ray crystallography. On the other hand, chloromethylated derivative 4 readily afforded large transparent crystals upon slow evaporation of a heptane/chloroform solution. Compound 4 crystallizes in the space group P21/c, without intramolecular symmetry (Z0 = 1).19,20 It adopts a pinched cone conformation (Fig. 1): one pair of opposite phenolic rings is almost parallel to each other, being pinched into the cavity with an interplanar angle of 7.95(6)°, whereas the second pair is widely open with an angle of 75.79(7)°. In the crystal, the calixarenes form loosely packed columns in which the bowls are stacked in the a direction. Side chains from neighboring molecules penetrate into the columns, mainly through the formation of non-classical weak hydrogen bonds21 in the direction of the pitched-out phenolic rings. Two chlorine atoms, located on the pitched-out phenolic rings, serve as 2-fold hydrogen bond acceptors. Two weak H-bonds involving hydrogens of chloromethylene groups are particularly short (2.65 and 2.75 Å). In the direction perpendicular to these interactions, where the calixarene rings are parallel to each other, there are CH–p interactions over an inversion center, connecting chloromethyl protons to the centroid of one of the benzene rings (2.93 Å). The UV/vis spectra of 1a–d (CH2Cl2, 293 K) showed the typical absorption pattern for tetrathio-substituted TTF derivatives with absorption bands at kmax ca. 310 and 330 nm, as well as a shoulder at ca. 390 nm.
As expected for calix[4]arenes in the cone conformation, 1H NMR spectra.13 presented two sets of the AB splitting patterns for the bridging diastereotopic methylene protons (ArCHaHbAr) of the calixarene bowl, with two pairs of doublets (2J = 13 Hz) belonging to two different types of CH2 bridges, lying either below or to the side of TTF groups (Fig. 2). The SCH2Ar protons of the TTF bridges also displayed the AB splitting patterns for the diastereotopic methylene protons (ArCHcHdS), with one pair of doublets (2J = 15.2 Hz), being an indication for the averaged C2v symmetry of the molecules. Furthermore, the signals of the aromatic protons of the calixarene bowl (He and Hf), especially those lying below the TTF bridges, were significantly broadened. Variable temperature NMR measurements with 1a and b were performed to give an insight into their conformational behavior.15 At lower temperatures, NMR spectra showed the splitting of the two aromatic signals into a pair of doublets, the strong broadening of one asymmetric proton belonging to ArCH2S bridges (Hd), the broadening and splitting of the signals, belonging to propyl chains,
Figure 2. VT-NMR of 1a. Signal indicated with (⁄) belong to residual CHDCl2.
M. H. Düker et al. / Tetrahedron Letters 52 (2011) 2881–2884
in pairs of broadened multiplets, as well as the splitting of the triplets, belonging to SCH2 groups (Hg), into two broad multiplets (Fig. 2). These spectroscopic data serve as an indication of desymmetrization of the calix[4]arene bowl into two degenerated pinched cone conformations and slowing down of the conformational interconversion between them at low temperatures. The splitting of the Hg triplets into two broad multiplets implies that two methylene groups become nonequivalent, which is likely to arise upon interaction of two closely spaced TTF moieties within an asymmetric closed conformation, such as the pinched cone. Thus, we could assume that the closed conformation should be the preferred one in solution, although intermolecular processes, such as dimerization of two molecules at lower temperatures, cannot be entirely ruled out. The electrochemical properties of calixarene–TTF conjugates 1a–d were investigated by cyclic voltammetry (CV) in dichloromethane/Bu4N+ ClO4 solutions (Fig. 3). Compounds 1a–d displayed the classical electrochemical behavior of tetrathiafulvalene derivatives, showing two quasi-reversible electrochemical processes on the cathodic scan, the first one at E1=2 1 = 0.30– 0.33 V (vs Ag/AgCl, Table 1) leading to the TTF radical cation, and the second one at E1=2 2 = 0.61–0.71 V, giving the dication. In contrast with the CVs of several other bis-tetrathiafulvalene derivatives,8,10d,22 the first oxidation wave did not display splitting, indicating that both TTF moieties are oxidized at the same potential and are not in electronic communication with each other in this type of compounds. Probably, the TTF–TTF interaction is disabled by the long distance between the two TTF moieties. Moreover, the cyclic voltammograms of compounds 1a–d showed additional oxidation waves at around 1.40 and 1.80 V, most likely arising from the oxidation of the calixarene cores. Calix[4]arenes are known to bind different electron-deficient guests inside their bowls,23,24 especially soft organic cations, by p–cation interactions. Molecular modeling has shown that quater-
2883
Figure 4. Structures of guests 6 and 7.
nary pyridinium salts can tightly fit inside the binding cavity formed by the calixarene and the TTF-molecular tweezers (Fig. 4). Binding studies25 were performed by NMR binding titrations in chloroform using compound 1b as a host and Nmethylpyridinium iodide (NMPI) 6 and 1-methyl-4-(methoxycarbonyl)pyridinium iodide 7 as guests.15 As expected, NMR spectra showed fast host–guest exchange and upfield shift of the guest resonances due to shielding effects of the benzene rings. Both guests 6 and 7 showed relatively weak binding with Ka = 7 ± 1 and 20 ± 2 m1, respectively. The parent calix[4]arene 3 displays only slightly lower binding efficiency with NMPI with Ka = 6.4 m1,23c,d implying that, in the case of receptors 1, binding is also mostly due to the p–cation interactions involving the calixarene bowl. This conclusion is supported by UV/vis spectra of the host/guest mixtures, which did not show the presence of any additional bands which could be contributed to charge-transfer interactions between host and guest molecules. The 4-fold alkyl substitution of the lower rim of 1a–d leads to the deformation of the calixarene bowl to the pinched cone conformation and is unfavorable for guest binding. Thus, the use of modified architectures with only two alkoxy substituents or two bridges on the lower rim connecting the neighboring hydroxyl groups is likely to increase the rigidity of the calix[4]arene bowl and improve the binding strength of the receptors, as it was shown before.24 Furthermore, pyrrolo-tetrathiafulvalenes,26 which are known for their better electron-donating and binding26c properties than thioalkyl-substituted TTFs, will be also tried as arms aiming to increase the binding efficiency. In summary, the first upper rim calixarene conjugates with upper rim tetrathiafulvalene bridges have been prepared and characterized using various physical methods. Calixarene–TTF conjugates showed moderate binding with pyridinium cations in solution. The synthesis of the modified upper rim TTF–calixarene conjugates both in cone and 1,3-alternate conformations of the calixarene bowl is currently in progress. Acknowledgments M.D. is grateful to BFK NaWi, University of Bremen, for financial support. We are thankful to Dr. T. Dülcks and Ms. D. Kemken (MS) and Mr. J. Stelten (NMR) for their help with the characterization of the new compounds. We are grateful to Matthias Zeller (STaRBURSTT Cyberinstrumentation Consortium, Youngstown State University, OH, USA) for collecting the X-ray data.
Figure 3. Cyclic voltammogram of TTF–calixarene conjugate 1a (CH2Cl2/0.1 m Bu4NClO4, scan rate 200 mV s1).
Supplementary data
Table 1 Electrochemical data of calixarene–TTF derivatives 1a
Supplementary data (all experimental procedures, 1D and 2D NMR spectra, NMR signal assignment, full VT-NMR spectra, details on molecular modeling, CV, crystallography, and binding studies) associated with this article can be found, in the online version, at doi:10.1016/j.tetlet.2011.03.140.
a
Compound
E1=2 ox1 (V)
E1=2 ox2 (V)
Eox3 (V)
1a 1b 1c 1d
0.30 0.33 0.31 0.33
0.66 0.61 0.61 0.71
1.40 (onset), 1.76 1.40 (onset), 1.82 1.45 (peak), 1.80 1.82
Data were obtained using a one-compartment cell in CH2Cl2/0.1 m Bu4NClO4, Pt as the working and counter electrodes. Values given at room temperature versus Ag/Ag+, scan rate 200 mV/s.
References and notes 1. For reviews and monographs on tetrathiafulvalenes, see: (a) Krief, A. Tetrahedron 1986, 42, 1209–1252; (b) Segura, J. L.; Martín, N. Angew. Chem., Int. Ed. 2001, 40, 1372–1409; (c) Fabre, J. M. Chem. Rev. 2004, 104, 5133–5150; Yamada, J.; Sugimoto, T. TTF Chemistry. Fundamentals and Applications of Tetrathiafulvalene; Springer: Heidelberg, 2004.
2884
M. H. Düker et al. / Tetrahedron Letters 52 (2011) 2881–2884
2. (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, D. F. Chem. Rev. 2004, 104, 4891–4945. 3. Canevet, D.; Sallé, M.; Zhang, G.; Zhang, D.; Zhu, D. Chem. Commun. 2009, 2245– 2269. 4. (a) Bryce, M. R.; Devonport, W.; Goldberg, 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. 5. (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. N. P.; Flood, A. H.; Fernández, J. M.; Stoddart, J. F. Top. Curr. Chem. 2005, 262, 99–132. 6. For comprehensive reviews and monographs on calixarenes, see: (a) Böhmer, V. Angew. Chem., Int. Ed. Engl. 1995, 34, 713–745; (b) Asfari, Z.; Böhmer, V.; Harrowfield, J.; Vicens, J. Calixarenes 2001; Kluwer Academic Publishers: Dordrecht, 2001; (c) Gutsche, C. D. Calixarenes. An Introduction, 2nd ed.; RSC: Cambridge, 2008. 7. For reviews on application of calixarenes, see: (a) Ikeda, A.; Shinkai, S. Chem. Rev. 1997, 97, 1713–1734; (b) Casnati, A.; Sansone, F.; Ungaro, R. Acc. Chem. Res. 2003, 36, 246–254; (c) Baldini, L.; Casnati, A.; Sansone, F.; Ungaro, R. Chem. Soc. Rev. 2007, 36, 254–266; (d) Lhoták, P. Top. Curr. Chem. 2005, 255, 65–95; (e) Rebek, J., Jr. Chem. Commun. 2000, 637–643; (f) Bogdan, A.; Rudzevich, Y.; Vysotsky, M. O.; Böhmer, V. Chem. Commun. 2006, 2941–2952; (g) Sansone, F.; Baldini, L.; Casnati, A.; Ungaro, R. New J. Chem. 2010, 34, 2715–2728. 8. (a) Azov, V. A.; Gómez, R.; Stelten, J. Tetrahedron 2008, 64, 1909–1917; (b) Skibin´ski, M.; Gómez, R.; Lork, E.; Azov, V. A. Tetrahedron 2009, 65, 10348– 10354. 9. (a) Regnouf-de-Vains, J.-B.; Sallé, M.; Lamartine, R. J. Chem. Soc., Perkin Trans 2 1997, 2461–2462; (b) Lee, M. H.; Cao, Q.-Y.; Kim, S. K.; Sessler, J. L.; Kim, J. S. J. Org. Chem. 2011, 76, 870–874. 10. (a) Zhao, B.-T.; Blesa, M.-J.; Mercier, N.; Le Derf, F.; Sallé, M. J. Org. Chem. 2005, 70, 6254–6257; (b) Zhao, B.-T.; Blesa, M.-J.; Mercier, N.; Le Derf, F.; Sallé, M. New J. Chem. 2005, 1164–1167; (c) Blesa, M.-J.; Zhao, B.-T.; Allain, M.; Le Derf, F.; Sallé, M. Chem. Eur. J. 2006, 12, 1906–1914; (d) Lyskawa, J.; Sallé, M.; Balandier, J.-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) Zhao, B.-T.; Chen, J.-Q.; Qu, G.-R. Chinese J. Org. Chem. 2007, 27, 1424–1427; (g) Lyskawa, J.; Canevet, D.; Allain, M.; Salle, M. Tetrahedron Lett. 2010, 51, 5868–5872. 11. (a) Zhao, B.-T.; Zhou, Z.; Yan, Z.-N.; Belhadj, E.; Le Derf, F.; Salle, M. Tetrahedron Lett. 2010, 51, 5815–5818; (b) Zhao, B.-T.; Guo, W.-B.; Hu, P.-Z. Heterocycles 2010, 81, 1661–1667. 12. (a) Nielsen, K. A.; Cho, W.-S.; Lyskawa, J.; Levillain, E.; Lynch, V. M.; Sessler, J. L.; Jeppesen, J. O. J. Am. Chem. Soc. 2006, 128, 2444–2451; (b) Nielsen, K. A.; Sarova, G. H.; Martín-Gomis, L.; Fernández-Lázaro, F.; Stein, P. C.; Sanguinet, L.; Levillain, E.; Sessler, J. L.; Guldi, D. M.; Sastre-Santos, Á.; Jeppesen, J. O. J. Am. Chem. Soc. 2008, 130, 460–462; (c) Nielsen, K. A.; Martín-Gomis, L.; Sarova, G. H.; Sanguinet, L.; Gross, D. E.; Fernández-Lázaro, F.; Stein, P. C.; Levillain, E.; Sessler, J. L.; Guldi, D. M.; Sastre-Santos, Á.; Jeppesen, J. O. Tetrahedron 2008, 64, 8449–8463; (d) Park, J. S.; Le Derf, F.; Bejger, C. M.; Lynch, V. M.; Sessler, J. L.; Nielsen, K. A.; Johnsen, C.; Jeppesen, J. O. Chem. Eur. J. 2010, 16, 848–854. 13. Frei, M.; Diederich, F.; Tremont, R.; Rodriguez, T.; Echegoyen, L. Helv. Chim. Acta 2006, 89, 2040–2057. 14. Only a few calix[4]arenes with rigid upper bridges have been reported: (a) Ikeda, A.; Shinkai, S. J. Chem. Soc., Perkin Trans 1 1993, 2671–2673; (b) Ikeda, A.; Yoshimura, M.; Lhotak, P.; Shinkai, S. J. Chem. Soc., Perkin Trans 1 1996, 1945– 1950. 15. See Supplementary data for additional details. 16. Characterization data of compound 1a: orange–yellow powder (59%); mp: 145– 150°C; Rf = 0.76 (CH2Cl2/PE, 1:1); 1H NMR (360 MHz, CDCl3): d = 0.88 (t, 3 J = 6.8 Hz, 12H), 1.02 (t, 3J = 7.6 Hz, 12H), 1.23–1.31 (m, 16H), 1.35–1.44 (m, 8H), 1.58–1.67 (m, 8H), 1.88–2.01 (m, 8H), 2.82 (t, 3J = 7.4 Hz, 8H), 3.01 (d, 2 J = 13.0 Hz 2H), 3.15 (d, 2J = 13.0 Hz, 2H), 3.55 (d, 2J = 15.2 Hz, 4H), 3.78 (t, 3 J = 7.2 Hz, 8H), 4.14 (d, 2J = 15.2 Hz, 4H), 4.30 (d, 2J = 13.0 Hz, 2H), 4.37 (d,
2
17.
18.
19. 20.
21. 22.
23.
24.
25. 26.
J = 13.0 Hz, 2H), 6.56 (br s, 4H), 6.79 (br s, 4H); 13C NMR (90 MHz, CDCl3): d = 10.4, 14.0, 22.5, 23.4, 28.2, 29.7, 29.8, 30.2, 31.3, 36.2, 39.3, 77.1, 108.5, 111.3, 127.6, 128.0, 128.2, 133.2, 134.3, 135.4, 155.2; UV–vis (CH2Cl2): kmax = 311 (36400), 333 (33000), 386 sh (11400 dm3 mol1 cm1) nm; MS (ESI+): m/z (%) 1640 (M+, 40), 1663 ([M+Na]+, 100), 1679 ([M+K]+, 80); HR-MS (MALDI, matrix: DCTB): m/z calcd for C80H104O4S16 (M+) 1640.3461, found 1640.3704. (a) Simonsen, K. B.; Svenstrup, N.; Lau, J.; Simonsen, O.; Mørk, P.; Kristensen, G. J.; Becher, J. Synthesis 1996, 407–418; (b) Svenstrup, N.; Rasmussen, K. M.; Hansen, T. K.; Becher, J. Synthesis 1994, 809–812. General procedure for the synthesis of 1: bis-cyanoethyl TTF derivative 5 (0.22 mmol) was dissolved in dry DMF (10 mL) and degassed by 2–3 freezepump-thaw cycles; then CsOH (0.46 mmol, 0.32 mL) was added as a 1.5 m solution in MeOH at 0 °C. The mixture was allowed to warm to rt and stirred for 30 min, changing its color from orange to dark brown–red. Calixarene 4 (0.1 mmol) was dissolved in dry THF (3 mL), and the solution was degassed by a freeze-pump-thaw cycle. Afterward the calixarene solution was added in one portion to the previously prepared thiolate solution at 20 °C, and then the mixture was allowed to warm to rt gradually. The reaction mixture turned orange–yellow, a yellow precipitate appeared for some derivatives. The reaction was allowed to stir for additional 30 min at rt, and then THF was removed under vacuum. The product was precipitated by addition of MeOH and filtered off. The residue was finally purified by flash chromatography (FC) on silica gel. The structure was solved and refined using SHELX: Sheldrick, G. M. Acta Cryst. 2008, A64, 112–122. Crystallographic data for 4: C44H52Cl4O4, M = 786.66, monoclinic, a = 14.021(2) Å, b = 17.163(3) Å, c = 17.520(3) Å, b = 100.600(2)°, V = 4144.1(12) Å3, T = 100(2) K, space group P21/c, Z = 4, 43438 reflections measured, 12758 independent reflections (Rint = 0.0291). The final R1 values were 0.0437 (I>2r(I)). The final wR(F2) values were 0.1142 (I>2r(I)). The final R1 values were 0.0556 (all data). The final wR(F2) values were 0.1257 (all data). GOF on F2 was 1.032. The data for the structure have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC813254. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, (fax: +44 (0)1223 336033 or email: [email protected]). Desiraju, G. R. Chem. Commun. 2005, 2995–3001; Steiner, T. Angew. Chem., Int. Ed. 2002, 41, 48–76. (a) Jørgensen, M.; Lerstrup, K. A.; Bechgaard, K. J. Org. Chem. 1991, 56, 5684– 5688; (b) Blanchard, P.; Svenstrup, N.; Becher, J. Chem. Commun. 1996, 615– 616; (c) Spanggaard, H.; Prehn, J.; Nielsen, M. B.; Levillain, E.; Allain, M.; Becher, J. J. Am. Chem. Soc. 2000, 122, 9486–9494; (d) Le Derf, F.; Levillain, E.; Trippé, G.; Gorgues, A.; Sallé, M.; Sebastian, R.-M.; Caminade, A.-M.; Majoral, J.-P. Angew. Chem., Int. Ed. 2001, 40, 224–227; (e) Bouguessa, S.; Hervé, K.; Golhen, S.; Ouahab, L.; Fabre, J.-M. New J. Chem. 2003, 27, 560–564. (a) Lhoták, P.; Shinkai, S. J. Phys. Org. Chem. 1997, 105, 273–285; (b) Araki, K.; Shimizu, H.; Shinkai, S. Chem. Lett. 1993, 205–208; (c) Araki, K.; Hayashida, H. Chem. Lett. 2000, 20–21; (d) Araki, K.; Hayashida, H. Tetrahedron Lett. 2000, 41, 1209–1213; (e) Arduini, A.; Pochini, A.; Secchi, A. Eur. J. Org. Chem. 2000, 2325– 2334; (f) Arduini, A.; Giorgi, G.; Pochini, A.; Secchi, A.; Ugozzoli, F. J. Org. Chem. 2001, 66, 8302–8308. (a) Arduini, A.; McGregor, W. M.; Paganuzzi, D.; Pochini, A.; Secchi, A.; Ugozzoli, F.; Ungaro, R. J. Chem. Soc., Perkin Trans 2 1996, 839–846; (b) Arena, G.; Contino, A.; Longo, E.; Spoto, G.; Arduini, A.; Pochini, A.; Secchi, A.; Massera, C.; Ugozzoli, F. New J. Chem. 2004, 28, 56–61; (c) Pescatori, L.; Arduini, A.; Pochini, A.; Secchi, A.; Massera, C.; Ugozzoli, F. Org. Biomol. Chem. 2009, 7, 3698–3708. For a review on determination of binding constants using NMR, see: Fielding, L. Tetrahedron 2000, 56, 6151–6170. (a) Jeppesen, J. O.; Takimiya, K.; Jensen, F.; Brimert, T.; Nielsen, K.; Thorup, N.; Becher, J. J. Org. Chem. 2000, 65, 5794–5805; (b) Jeppesen, J. O.; Becher, J. Eur. J. Org. Chem. 2003, 3245–3266; (c) Nielsen, M. B.; Jeppesen, J. O.; Lau, J.; Lomholt, C.; Damgaard, D.; Jacobsen, J. P.; Becher, J.; Stoddart, J. F. J. Org. Chem. 2001, 66, 3559–3563.