Synthesis, conformational studies and inclusion properties of O-benzylated calixarene analogues of trihydroxy[3.3.3]metacyclophanes

Abstract

O-Benzylation of the flexible macrocycle 1 with benzyl bromide in the presence of NaH in THF under reflux afforded a mixture of two conformers of the tri-O-benzylated products, cone-2a and partial-cone-2a in a ratio of 20∶80 in 80% yield. In contrast, O-alkylation of the triol 1 with 2-(chloromethyl)pyridine in the presence of NaH resulted in exclusive formation of cone-2b. Only when the template metal can hold the 2-pyridyl group(s) and the oxide group(s) on the same side of the [3.3.3]metacyclophane ring, is the conformation immobilized in the cone form. The template effect of the sodium cation plays an important role in this benzylation.

The two-phase solvent extraction data indicated that tris(2-pyridylmethoxy)[3.3.3]metacyclophanes 2b show strong Ag⁺ affinity, high Ag⁺ selectivity being observed for both cone-2b and partial-cone-2b. ¹H NMR Titration of cone-2b with AgSO₃CF₃ clearly demonstrates that a 1∶1 complex is formed with retention of the original symmetry. The pyridine moiety underwent conformational changes upon Ag⁺ complexation with the original outward orientation of the ring nitrogen changing to an inside orientation toward the cyclophane cavity.

References

1. (a) C. D. Gutsche, Calixarenes, Royal Society of Chemistry, Cambridge, 1989; (b) J. Vicens and V. Böhmer, CALIXARENES: A Versatile Class of Macrocyclic Compounds, Kluwer Academic Publishers, Cambridge, 1990; (c) V. Böhmer, Angew. Chem., Int. Ed. Engl., 1995, 34, 713.
2. (a) C. D. Gutsche, Acc. Chem. Res., 1983, 16, 161; (b) J.-D. van Loon, L. C. Groenen, S. S. Wijmenga, W. Verboom and D. N. Reinhoudt, J. Am. Chem. Soc., 1991, 113, 2378; (c) L. C. Groenen, J.-D. van Loon, W. Verboom, S. Harkema, A. Casnati, R. Ungaro, A. Pochini, F. Ugozzoli and D. N. Reinhoudt, J. Am. Chem. Soc., 1991, 113, 2385; (d) K. Iwamoto, K. Araki and S. Shinkai, J. Chem. Soc., Perkin Trans. 1, 1991, 1611; (e) K. Araki, K. Iwamoto, S. Shinkai and T. Matsuda, Chem. Lett., 1989, 1747; (f) K. Iwamoto, K. Araki and S. Shinkai, Tetrahedron, 1991, 47, 4325; (g) K. Iwamoto, K. Araki and S. Shinkai, J. Org. Chem., 1991, 56, 4955.
3. T. Yamato, L. K. Doamekpor, K. Koizumi, K. Kishi, M. Haraguchi and M. Tashiro, Liebigs Ann., 1995, 1259.
4. (a) K. Araki, N. Hashimoto, H. Otsuka and S. Shinkai, J. Org. Chem., 1993, 58, 5958; (b) K. Araki, K. Inada, H. Otsuka and S. Shinkai, Tetrahedron, 1993, 49, 9465; (c) K. Araki, K. Inada, H. Otsuka and S. Shinkai, Tetrahedron, 1995, 51, 4647; (d) K. Araki, K. Inada and S. Shinkai, Angew. Chem., Int. Ed. Engl., 1996, 35, 72.
5. (a) S. Pappalardo, L. Giunta, M. Foti, G. Ferguson, J. F. Gallagher and B. Kaitner, J. Org. Chem., 1992, 57, 2611; (b) G. Ferguson, J. F. Gallagher, L. Giunta, P. Neri, S. Pappalardo and M. Parisi, J. Org. Chem., 1994, 59, 42; (c) S. Pappalardo, New J. Chem., 1996, 20, 465.
6. J. M. Harrowfield, M. I. Ogden, W. R. Richmond and A. H. White, J. Chem. Soc., Chem. Commun., 1991, 1159.
7. (a) B. H. Smith, in Bridged Aromatic Compounds, Academic Press, New York, 1964; (b) F. Vögtle and P. Neumann, Angew. Chem., 1972, 84, 75; Angew. Chem., Int. Ed. Engl., 1972, 11, 73; (c) F. Vögtle and P. Neumann, Synthesis, 1973, 85; (d) F. Vögtle and G. Höhner, Top. Curr. Chem., 1978, 74, 1; (e) P. M. Keehn and S. M. Rosenfield, Cyclophanes, Academic Press, New York, 1983, vol. 1; (f) F. Vögtle, Cyclophane Chemistry, John Wiley, New York, 1993.
8. (a) M. Tashiro and T. Yamato, J. Org. Chem., 1981, 46, 4556; (b) M. Tashiro and T. Yamato, J. Org. Chem., 1983, 48, 1461.
9. (a) A. Arduini, A. Pochini, S. Reverberi and R. Ungaro, Tetrahedron, 1986, 42, 2089; (b) G. D. Andreetti, G. Calestani, F. Ugozzoli, A. Arduini, E. Ghidini, A. Pochini and R. Ungaro, J. Incl. Phenom., 1987, 5, 123.
10. (a) M. A. McKervey, E. M. Seward, G. Ferguson, B. Ruhl and S. Harris, J. Chem. Soc., Chem. Commun., 1985, 388; (b) F. Arnaud-Neu, E. M. Collins, M. Deasy, G. Ferguson, S. J. Harris, B. Kaitner, A. J. Lough, M. A. McKervey, E. Marques, B. Ruhl, M. J. Schwing-Weill and E. M. Seward, J. Am. Chem. Soc., 1989, 111, 8681.
11. S. K. Chang and I. Cho, J. Chem. Soc., Perkin Trans. 1, 1986, 211.
12. (a) T. Arimura, M. Kubota, T. Matsuda, O. Manabe and S. Shinkai, Bull. Chem. Soc. Jpn., 1989, 62, 1674; (b) K. Iwamoto and S. Shinkai, J. Org. Chem., 1992, 57, 7066; (c) N. Sato and S. Shinkai, J. Chem. Soc., Perkin Trans. 1, 1993, 2621.
13. R. Vreekamp, W. Verboom and D. N. Reinhoudt, J. Org. Chem., 1996, 61, 4282.
14. S. Inokuma, S. Yasuda, S. Araki, S. Sakai and J. Nishimura, Chem. Lett., 1994, 201.
15. H. Tsukube, T. Yamashita, M. Iwaxhido and M. Zenki, J. Org. Chem., 1991, 56, 268.
16. A. Ikeda and S. Shinkai, J. Am. Chem. Soc., 1994, 116, 3102.
17. C. J. Pedersen, J. Am. Chem. Soc., 1967, 89, 2495.