Synthesis and conformational studies of tetrahydroxy[3.1.3.1]metacyclophanes and electrophilic aromatic substitution of their tetramethoxy derivatives

Abstract

Base-catalysed condensation of 1,3-bis(5-tert-butyl-2-hydroxyphenyl)propane 5 with formaldehyde in xylene has been carried out to form the novel propane-bridged calixarene-type macrocyclic compound, tetrahydroxy[3.1.3.1]metacyclophane 6. The optimum yield (90%) of 6 is obtained with NaOH as the base, the use of other alkali-metal hydroxides giving lower yields. AlCl₃–MeNO₂-catalysed trans-tert-butylation of 6 in benzene affords 7 in 80% yield. Intramolecular hydrogen bonding has been observed in the tetraols 6 and 7 as comparable to calix[4]arene. Methylation of 7 with MeI affords the tetramethoxy derivative 11a. The stability of multi-membered carbon skeletons permits the interconversion of functional groups at the lower and upper rims without special regard to ring-opening side-reactions on the upper rim. For example, the introduction of Br, formyl and acetyl substituents has been achieved by electrophilic aromatic substitution of the tetramethoxy derivative 11a. The ¹H NMR spectral behaviour of these macrocyclic metacyclophanes is also discussed.

References

1. For a comprehensive review of all aspects of calixarene chemistry, see: (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) C. D. Gutsche, Acc. Chem. Res., 1983, 16, 161.
2. C. D. Gutsche, B. Dhawan, K. H. No and R. Muthukrishnan, J. Am. Chem. Soc., 1981, 103, 3782.
3. (a) K. Iwamoto, K. Araki and S. Shinkai, J. Chem. Soc., Perkin Trans. 1, 1991, 1611; (b) K. Araki, K. Iwamoto, S. Shinkai and T. Matsuda, Chem. Lett., 1989, 1747; (c) K. Iwamoto, K. Araki and S. Shinkai, Tetrahedron, 1991, 47, 4325; (d) K. Iwamoto, K. Araki and S. Shinkai, J. Org. Chem., 1991, 56, 4955; (e) K. Iwamoto and S. Shinkai, J. Org. Chem., 1992, 57, 7066.
4. (a) J.-D. van Loon, L. C. Groenen, S. S. Wijmenga, W. Verboom and D. N. Reinhoudt, J. Am. Chem. Soc., 1991, 113, 2378; (b) 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.
5. (a) M. Tashiro, A. Tsuge, T. Sawada, T. Makishima, S. Horie, T. Arimura, S. Mataka and T. Yamato, J. Org. Chem., 1990, 55, 2404; (b) T. Yamato, Y. Saruwatari, S. Nagayama, K. Maeda and M. Tashiro, J. Chem. Soc., Chem. Commun., 1992, 861; (c) F. Vögtle, J. Schmitz and M. Nieger, Chem. Ber., 1992, 125, 2523; (d) T. Yamato, K. Hasegawa, Y. Saruwatari and L. K. Doamekpor, Chem. Ber., 1993, 126, 1435; (e) T. Yamato, Y. Saruwatari, L. K. Doamekpor, K. Hasegawa and M. Koike, Chem. Ber., 1993, 126, 2501.
6. (a) T. Yamato, J. Matsumoto, M. Kajihara and M. Tashiro, Chem. Express, 1990, 5, 769; (b) T. Yamato, J. Matsumoto, S. Ide, K. Tokuhisa, K. Suehiro and M. Tashiro, J. Org. Chem., 1992, 57, 5243; (c) T. Yamato, J. Matsumoto, K. Tokuhisa, M. Kajihara, K. Suehiro and M. Tashiro, Chem. Ber., 1992, 125, 2443.
7. (a) M. Tashiro and T. Yamato, Synthesis, 1981, 435; (b) M. Tashiro and T. Yamato, J. Am. Chem. Soc., 1982, 104, 3701; (c) M. Tashiro, K. Koya and T. Yamato, J. Am. Chem. Soc., 1982, 104, 3707; (d) T. Yamato, J. Matsumoto, K. Tokuhisa, K. Tsuji, K. Suehiro and M. Tashiro, J. Chem. Soc., Perkin Trans. 1, 1992, 2675.
8. (a) C. D. Gutsche, Acc. Chem. Res., 1983, 16, 161; (b) C. D. Gutsche and L. J. Bauer, J. Am. Chem. Soc., 1985, 107, 6052.
9. M. F. Semmelhack, J. J. Harrison, D. C. Young, A. Gutiérrez, S. Rafii and J. Clardy, J. Am. Chem. Soc., 1985, 107, 7508.
10. (a) R. W. Griffin, Jr., Chem. Rev., 1963, 63, 45; (b) D. J. Cram, Acc. Chem. Res., 1971, 4, 204; (c) C. J. Brown, J. Chem. Soc., 1953, 3278; (d) B. H. Smith, Bridged Aromatic Compounds, Academic Press Inc., New York, 1964; (e) Cyclophanes, ed. P. M. Keehn and S. M. Rosenfield, Academic Press, New York, 1983, vol. 1, ch. 6, p. 428.
11. C. D. Gutsche and J. A. Levine, J. Am. Chem. Soc., 1982, 104, 2652.
12. (a) S. Shinkai, S. Mori, T. Tsubaki, T. Sone and O. Manabe, Tetrahedron Lett., 1984, 25, 5315; (b) S. Shinkai, H. Koreishi, S. Mori, T. Sone and O. Manabe, Chem. Lett., 1985, 1033; (c) S. Shinkai, S. Mori, H. Koreishi, T. Tsubaki and O. Manabe, J. Am. Chem. Soc., 1986, 108, 2409; (d) S. Shinkai, K. Araki, H. Koreishi, T. Tsubaki and O. Manabe, Chem. Lett., 1986, 1351; (e) T. Arimura, H. Kawabata, T. Matsuda, T. Muramatsu, H. Satoh, K. Fujio, O. Manabe and S. Shinkai, J. Org. Chem., 1991, 56, 301.
13. S. Shinkai, T. Tsubaki, T. Sone and O. Manabe, Tetrahedron Lett., 1985, 26, 3323.
14. (a) J.-D. van Loon, R. G. Janssen, W. Verboom and D. N. Reinhoudt, Tetrahedron Lett., 1992, 33, 5125; (b) P. D. Beer, P. A. Gale and D. Hesek, Tetrahedron Lett., 1995, 36, 767; (c) W. Verboom, A. Durie, R. J. M. Egberink, Z. Asfari and D. N. Reinhoudt, J. Org. Chem., 1992, 57, 1313; (d) W. Verboom, P. J. Bodewes, G. Essen, P. Timmerman, G. J. van Hummel, S. Harkema and D. N. Reinhoudt, Tetrahedron, 1995, 51, 499; (e) J. Scheerder, M. Fochi, J. F. J. Engbersen and D. N. Reinhoudt, J. Org. Chem., 1994, 59, 7815; (f) J. Scheerder, J. F. J. Engbersen, A. Casnati, R. Ungaro and D. N. Reinhoudt, J. Org. Chem., 1995, 60, 6448.
15. (a) K. Araki, N. Hashimoto, H. Otsuka and S. Shinkai, J. Org. Chem., 1993, 58, 5958; (b) K. Araki, K. Inaba, H. Otsuka and S. Shinkai, Tetrahedron, 1993, 49, 9465; (c) M. Takeshita and S. Shinkai, Chem. Lett., 1994, 125.
16. C. D. Gutsche, M. Igbal and I. Alam, J. Am. Chem. Soc., 1987, 109, 4314.