J. Am. Chem. SOC.1995,117, 2767-2777
2767
Synthesis, Complexation, and Membrane Transport Studies of 1,3-Alternate Calix[4]arene-crown-6 Conformers: A New Class of Cesium Selective Ionophores Alessandro Casnati,? Andrea Pochini,? Rocco Ungaro,*J Franco Ugozzoli,’ Franqoise Arnaud,s Stefan0 Fanni? Marie-Josh Schwing,*$s Richard J. M. Egberink? Feike de Jong,l and David N. Reinhoudt*s Contribution from the Dipartimento di Chimica Organica e Industriale and Dipartimento di Chimica Generale ed Inorganica, Analitica, Chimica Fisica e Centro di Studio per la Strutturistica Di’attometrica del CNR, Universith degli Studi, Viale delle Scienze 78, I-43100 Parma, Italy, Laboratoire de Chimie-Physique, URA 405 au CNRS, EHICS, I rue Blaise Pascal, 67000 Strasbourg, France, and Laboratory of Organic Chemistry, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands Received October 6, 1994@
Abstract: 1,3-Dialkoxycalix[4]arene-crown-6 ionophores (4a-d) are obtained in the fixed 1,3-alternateconformation in 63-85% yield by the reaction of the corresponding 1,3-dialkoxycalix[4]arenes3a-d with pentaethylene glycol ditosylate in CH3CN in the presence of CszCO3. The corresponding cone conformer of the diisopropyl derivative (6) was synthesized via selective demethylation of the 1,3-dimethoxycalix-crown(2a) and subsequent dialkylation. Extraction experiments with alkali picrates reveal a strong preference of ligands 4 for Cs+. Thermodynamic parameters obtained for the complexation of 4a show that the high stability constant in MeOH (logp = 6.4 f 0.4) is reflected mainly in the large -AH,value of 50.2 f 0.2 kJ mol-’. The entropy of complexation (TAS, = - 15 kJ mol-’), less negative than for other crown ethers, is explained in terms of preorganization of 4a. The X-ray structure of the cesium picrate 4a complex shows clearly that the cation is positioned between the two aromatic rings with short Cs-C distances of 3.49 and 3.69 A, respectively. ‘H NMR spectroscopy confirms this type of structure in solution. Ligands 4 incorporated in supported liquid membranes transport Cs+ cations with a high preference over Na+. By the application of an anion gradient, traces of Cs+ can be removed (199.8%) from acidic solutions (pH = 0) that contain 4 M of NaN03.
Introduction The present work had its beginning with the studies of Ungaro and co-workers’ involving the use of calixarenes* as building blocks or molecular platforms for the construction of metal ion l i g a n d ~ . It ~ is now well-established that the efficiency and selectivity in metal ion binding by calixarene ionophores depends not only on the ring size of the calix but also on the nature of the binding groups attached and, especially for calix[4]arene derivatives, on the conformation of the macrocycle (cone, partial cone, 1,3-alternate, 1,2-altemate). Ungaro and co-workers have previously reported the synthesis, structure, and complexing properties of several stereoa isomers of 1,3-dialkoxy-p-tert-butylcalix[4]arene-crown-5~ t Dipartimento di Chimica Organica e Industriale.
*
Dipartimento di Chimica Generale ed Inorganica, Analitica, Chimica Fisica e Centro di Studio per la Strutturistica Diffrattometrica del CNR. 6 Laboratoire de Chimie-Physique. Laboratory of Organic Chemistry. @Abstractpublished in Advance ACS Abstracts, February 1, 1995. (1) Bocchi, V.; Fiona, D.; Pochini, A.; Ungaro, R. Tetrahedron 1982, 38, 373-378. (2) For recent review articles and books on calixarenes,see: (a) Gutsche, C. D. Calixarenes, Monographs in Supramolecular Chemistry; Stoddart, J. F., Ed.; Royal Society of Chemistry: Cambridge, U.K., 1989; Vol. 1. (b) Calixarenes, A Versatile Class of Macrocyclic Compounds; Vicens, J., Bohmer, V., Eds.; Kluwer, Academic Publishers: Dordrecht, The Netherlands, 1991. (c) Gutsche, C. D. In Inclusion Compounds; Atwood, J. L., Davies, J. E. D., MacNicol, D. D., Eds.; Oxford University Press: New York, 1991; Vol. 4, pp 27-63. (d) Van Loon, J.-D.; Verboom, W.; Reinhoudt, D. N. Org. Prep. Proced. Int. 1992, 24, 437-462. (e) Shinkai, S. Tetrahedron 1993,40,8933-8968. (0 Bohmer, V. Angew. Chem. 1994, in press. (g) Pochini, A,; Ungaro, R. In Comprehensive Supramolecular Chemistry; Vogtle, F., Ed.; Pergamon Press, in press; Vol. 2. 0002-7863/95/1517-2767$09.00/0
new class of potassium selective ligands. Their ionophoric properties5 as well as their selectivity in metal detection by ionselective field effect transistors6 strongly depend on the stereochemistry around the binding region. Interestingly, Yamamoto and Shinkai7 have reported that the corresponding calix[4]arenecrown-4, with a shorter polyethylene glycol bridge, shows a very high inverse K+/Na+ selectivity in ion-selective electrodes. We have investigated the combination of calix[4]arenes and crown ether bridges for the problem of selective removal of 137Cs+from medium level radioactive waste, an important environmental and technological p r ~ b l e m . ~The . ~ objective was to selectively extract long-lived 137Csisotopes from an aqueous solution containing 1 M HNO3 and 4 M NaNO3. (3) For recent review articles on the inclusion properties of calixarenes, see: Ungaro, R.; Pochini, A. in ref 2b, pp 127-147. Ungaro, R.; Pochini, A. In Frontiers in Supramolecular Organic Chemistry and Photochemistry; Schneider, H.-J., Eds.; VCH: Weinheim, Gemany, 1991; pp 57-81. Andreetti, G. D.; Ugozzoli, F.; Ungaro, R.; Pochini, A. In Inclusion Compounds; Atwood, J. L., Davies, J. E. D., Mac Nicol, D.D., Eds.; Oxford University Press: New York, 1991; Vol. 4, pp 64-125. Van Doom, A. R.; Verboom, W.; Reinhoudt, D.N. In Adv. Supramol. Chem. 1993, 3, 160206. Ungaro, R.; Arduini, A.; Casnati, A,; On, 0.; Pochini, A.; Ugozzoli, F. In Computational Approaches in Supramolecular Chemistry; Wipff, G., Ed.; Kluwer Academic, Publishers: Dordrecht, The Netherlands, 1994;pp 277-300. (4) (a) Dijkstra, P. J.; Brunink, J. A. J.; Bugge, K.-E.; Reinhoudt, D. N.; Harkema, S.; Ungaro, R.; Ugozzoli, F.; Ghidini, E. J. Am. Chem. SOC.1989, I l l , 7567-7575. (b) Ghidini, E.; Ugozzoli, F.; Ungaro, R.; Harkema, S.; El-Fadl, A. A; Reinhoudt, D. N. J. Am. Chem. SOC. 1990, 112, 69796985. ( 5 ) Nijenhuis, W. F.; Buitenhuis, E. G.; de Jong, F.; Sudholter, E. J. R.; Reinhoudt, D.N. J. Am. Chem. SOC. 1991, 113, 7963-7968. (6) Brzozka, 2.;Lammerink, B.; Reinhoudt, D. N.; Ghidini, E.; Ungaro, R. J. Chem. SOC., Perkin Trans. 2 1993, 1037-1040. (7)Yamamoto, J.; Shinkai, S. Chem. Lett. 1994, 1115-1118.
0 1995 American Chemical Society
2168 J. Am. Chem. SOC.,Vol. 117, No.
IO, 1995
Casnati et al.
Scheme 1
3 1
U R
4
a: CH(CH,),
b: CH,CH,CH, c: (CH,),CH, d: CH,(CH,).CH,OQ O,N
Za: n = 6. R = H
R
b: n = 6. R = t-Bu c: n = 5, R = H
d: n = 7, R = H
R
In this paper we report that 1,3-dialkoxycalix[4]arene-crown6 derivatives, when they are fixed in the 13-alternate conformation, are exceptionally selective ionophores for cesium cations. The properties of these new ligands have been assessed by NMR, two-phase solvent extraction, thermodynamic studies in solution, and X-ray crystal structure determination of their cesium complexes. Their application in supported liquid membranes revealed that it is possible to remove cesium salts selectively from strongly acidic solutions that contain 4 M NaN03. By anion-driven transport against the concentration gradient 299.8% of traces of cesium can be removed within 24 h.
Results and Discussion Synthesis and Conformational Properties of the Ionophores. The X-ray crystal structure of the cesium picrate complex of the 1,3-dimethoxycalix[4]arene-crown-6(2a) revealed that this conformationally mobile ligand adopts a 1,3altemate conformation in the complex.10 Therefore further work focused on the synthesis of calix[4]crown-6 derivatives having a fixed 1,3-altemate structure. Previously Reinhoudt and coworkers have shown that the reaction of calix[4]arenes with (8) Radioactive Waste Management and Disposal; Cecille, L., Ed.; Elsevier Science Publisher: London, New York, 1991. (9) McDowell, W. J.; Case, G. N.; McDonough, J. A.; Bartsch, R. A. Anal. Chem. 1992, 64, 3013-3017. (10) Ungaro, R.; Casnati, A.; Ugozzoli, F.; Pochini, A.; Dozol, J.-F.; Hill, C.; Rouquette, H. Angew. Chem., Inr. Ed. Engl. 1994, 33, 15061509.
alkylating agents in CH3CN in the presence of C S ~ C Ois J a well established method to obtain tetraalkoxycalix[4]arenes fixed in the 1,3-altemate conformation." When we applied this method (Scheme 1) to 1,3-dialkoxycalix[4]arenes (3), prepared from calix[4]arene 1 with alkyl halides in CH3CN in the presence of K2CO3, we obtained the calix[4]crown-6 ethers (4) in a fixed 1,3-altemate conformation. No other isomers were isolated. Possibly the cyclization reaction to give the 1,3-altemate conformers is favored by the cesium template ions. All compounds 4 are blocked in the 1,3-altemate conformation as inferred from the 'H NMR spectra which exhibit a singlet around 6 3.8 for the bridging methylene groups of the calix[4]arene moiety. The I3C NMR spectra show one signal around 38 ppm, characteristic for antioriented nuclei in the calix.12 The 1,3diisopropoxy cone isomer (6) was synthesized via 5 by first bridging calix[4]arene 1 with pentaethylene glycol ditosylate in benzene with KOt-Bu as the base. The yield of 1,3dihydroxycalix[4]arene-crown-6 was only 34%. An altemative route (Scheme 2) to 5 involves the reaction of 1,3-dimethoxycalix[4]arene-crown-6 (2a) with trimethylsilyl iodide that produces 5 in 84%. This very selective demethylation procedure13seems not to affect the crown ether moiety and may provide a general ethers method for the synthesis of dihydroxycalix[4]arene-~rown (1 1) Verboom, W.; Datta, S.; Asfari, Z.; Harkema, S.; Reinhoudt, D. N. J. Org. Chem. 1992, 57, 5394-5398. (12) Molins, M. A,; Nieto, P. M.; Sanchez, C.; Prados, P.; de Mendoza, J.; Pons, M. 0. J. Org. Chem. 1992, 57, 6924-6931. ( 13) Casnati, A.; Arduini, A.; Ghidini, E.; Pochini, A,; Ungaro, R. Tetrahedron 1991, 47, 2221-2228.
Studies of 1,3-Alternate Calix[4]arene-crown-6 Conformers
J. Am. Chem. Soc., Vol. 11 7, No. 10, 1995 2769
Scheme 2
-
NaH -b DMF i-Prl
TMSI CHCI,
I 2a
I 6
5
Table 1. Conformers Distribution and NMR Aromatic Signals for Compound 2a in Different Solvents at -25 "C
Table 2. Extraction Percentage of Alkali Picrates by Calix-crowns, from Water to Dichloromethane, at 20 "C
solvent conformation % CD3CN cone 50 partialcone 35 1,3-alternate 15 CDC13 cone 60 partial cone 25 1,3-altemate 15 CD3OP cone 64
ligands
a
ArH 7.18 (d), 6.90 (t), 6.52 (d), 6.42 (t) 7.17,7.14, 6.93-6.88, 6.56 7.32 (d), 7.09 (d), 7.00 (t), 6.84 (t) 7.19 (d), 6.97 (t), 6.40 (m) 7.24,7.21,6.97,6.61(t), 6.56(dd), 6.43 7.33 (d), 7.11 (d), 6.99 (t), 6.85 (t) 7.1 1 (d), 6.87 (t), 6.30 (m)
2a 2b 2c 4a 4b 4c
2d 6
Li+
Na+
0.4 k 0.2 0.67 f 0.07 1.4 f 0.2 1.6 f 0.4 2 i0.4 1.6 f 0.3 3.0 iz 0.4 2.4 f 0.1 2.5 f 0.5 2.6 f 0.6 2.1 f 0.3 2.2 f 0.3 0.5 f 0.4 0.21 f 0.08 50.2 50.2
K+
Rb+
cs+
1.0 f 0.1 2.2 f 0.3 10f 1 15.8 f 0.5 13.8f 0.4 13.4 f 0.8 0.4 f 0.1 50.2
2.3 f 0.2 3.1 f 0.5 8.9 f 0.9 43.8 f 0.7 41.7 f 0.3 40.0 f 0.9 0.4 f 0.1 50.2
6.3 f 0.2 19.0f 0.7 2.8 f 0.3 64.5 f 0.7 63.5 f 0.3 63.9 iz 0.3 0.5 f 0.1 50.2
At +25 "C.
lipophilic alkali metal ion complexing agents,18 including other which are difficult to obtain by direct b1idging.4~3'~The reaction calix-crowns? The results of these studies are reported in Table of 5 with isopropyl bromide in DMF with NaH as the base, a 3. Both types of experiments reveal a high preference of ligands standard procedure for the synthesis of cone conformer^,^^ 4 fixed in the 1,3-altemate conformation for Cs+. The corproduced 6 in 73% yield. In the 'H NMR spectrum the ArCH2responding cone conformer 6 hardly extracts or binds Cs+. Ar protons of 6 give an AX system (6 3.14 and 4.38 ppm) and Complexation data (logp) for conformationally mobile calixin the 13CNMR a triplet (6, = 3 1.6 ppm), which are both typical crowns-6 (2a,b) and for compounds 4a and 4b, blocked in the for a fixed cone conformation.l* The conformationally mobile 1,3-altemate conformation and alkali metal cations in MeOH 1,3-dimethoxycalix[4]arene-crown ethers (2) were synthesized are reported in Table 4 and Figure 1. These data were obtained from the 1,3-dimethoxycalix[4]arenes and the appropriate by UV absorption spectrophotometry and by competitive polyethylene glycol ditosylates. They are conformationally potentiometric measurements. The logp values for the silver mobile in solution; detailed VT-'H NMR studies have been complexes are also reported as their determination was necessary performed only on compound 2a in two different solvents CD3for the interpretation of the competitive potentiometric measureCN and CDCl3. The room temperature 'H NMR spectrum of ments. Table 5 reports the thermodynamic parameters (AHc 2a is composed of sharp and broad peaks in all regions, which and TAS,) for the complexation, determined by calorimetry. indicate the presence of three conformations, one of which (the There is full agreement between the extraction and the cone) is kinetically stable (on the 400 MHz time scale) whereas complexation data for the calix-crowns reported. Among the the other two are in rapid equilibrium. At T = -25 "C the conformationally mobile 1,3-dimethoxy compounds 2 the signals of the three conformations are clearly visible in both crown-5 (2c) shows selectivity for potassium ion, the calixsolvents, and by integration of the aromatic region their relative crown-7 (2d) is completely unselective and quite inefficient, abundance was established (Table 1). whereas the crowns-6 (2a and 2b) show selectivity for cesium In both solvents the thermodynamically most stable conformer cation. The tert-butyl derivative 2b is slightly more efficient of 2a is the cone, followed by partial cone and 1,3-altemate. than the unsubstituted analog 2a. The cone conformation is also the most stable for compounds A dramatic increase in the binding and extraction of cesium 2b-d; a "flattened cone" structure has been found in the solid state for the 1,3-dimethoxy-p-tert-butylcalix[4]arene-cro~n-5~~ cation is observed for all ligands in the 1,3-altemate conformation. Complexation Studies A stereochemical dependence of alkali metal ion complexation was previously observed in potassium selective ionophores, A first estimation of the ionophoric properties of ligands 2, the 1,3-diethoxy-p-tert-butylcalix[4]arene-crowns-5,4b but the 4, and 6 was accomplished by the picrate extraction method difference between cone and partial cone or 1,3-altemate developed by Pedersen.16 The results are reported in Table 2 . conformers was not as large as that observed in this case for We also determined association constants in wet CHCl3, using the two conformers 6 (cone) and 4a (1,3-altemate). Probably the picrate extraction method reported by Lein and Cram17 which the presence of two bulky isopropoxy groups decreases for steric is more quantitative and allows a direct comparison of the reasons, the already low binding ability of the cone isomer, ionophoric properties of compound 2a,b, 4a,b, and 6 with other especially toward the larger cations. Interestingly all calix[4]arene-crowns-6 in the 1,3-altemate conformation (4) do not (14)Yamamoto, H.; Sakaki, T.;Shinkai, S. Chem. Left. 1994,469472. (17) (a) Lein, G. M.; Cram, D. J. J. Am. Chem. SOC. 1985,107,448(15) Groenen, L. C.; Ruel, B. H. M.; Casnati, A.; Timerman, P.; 455. (b) Helgeson, R. C.; Weisman, G. R.; Toner, J. L.; Tamowski, T. L.; Verboom, W.; Harkema, S.; Pochini, A.; Ungaro, R.; Reinhoudt, D. N. Chau, L.; Mayer, J. M.; Cram, D. J. J. Am. Chem, SOC. 1979,101, 4928Tetrahedron Lett. 1991,32,2675-2678. 4941. (16) Pedersen, C. J. Fed. Proc. Fed. Am. SOC.Expl. Bid. 1968,27,1305(18) Cram, D. J. Angew. Chem., Int. Ed. Engl. 1986,25, 1039-1057. 1309
2770 J. Am. Chem. Soc., Vol. 117, No. IO, 1995
Casnati et al.
Table 3. Association Constants (Ka)and Binding Free Energies (-AG) of Complexes of Hosts with Alkali Picrates in CHC13 Saturated with H20 at 22 "C"
ligand 4a 4b 2a 2b
Li+
Na+
b 5.5 b
5.2 5.1 4.3 4.6
4.7
