Linear and macrocyclic ligands containing alternating pyridine and imidazolidin-2-one units ¹

Abstract

Linear oligomers of alternating 2,6-disubstituted pyridine (P) and N,N ′-disubstituted imidazolidine-2-one (I) units have been made rapidly and in high yield with up to nine repeating units, terminating in either pyridine or imidazolidin-2-one units, or one of each. Synthetic methods include: (1) the sodium hydride-mediated condensation of N-(tert-butyl)imidazolidin-2-one with 2,6-difluoropyridine (F-P-F ) or with higher analogues such as F-PIP-F, to give IPI, IPIPI and IPIPIPI. (The tert-butyl protection is readily and quantitatively removed with acid.) (2) The caesium fluoride catalysed interaction of N,N ′-[dimethyl-(1,1,3-trimethylpropyl)]-protected IPI with Bu^t-IP-F sequentially leads firstly to IPIPIPI which by the same method reacts with F-P-F to give F-PIPIPIPIP-F. (3) F-P-F also reacts with 1,2-ethylenediamine (E) sequentially to give F-PEP-F, EPEPE and F-PEPEPEP-F while similar reactions starting from F-PIP-F give EPIPE and F-PEPIPEP-F in sequence. Alternative routes examined include: (1) the interaction of F-P-F with imidazole to give 2,6-bis(imidazol-1-yl)pyridine and salts therefrom followed by (unsuccessful) oxidation. (2) The reaction of 2,6-diaminopyridine with 2-chloroethyl isocyanate followed by cyclisation to give IPI. (3) The interaction of 2,6-diaminopyridine with oxalate esters (O) to give OPO or H₂N-POP-NH₂, the latter of which was reduced to H₂N-PEP-NH₂.

Cyclisation of the linear assemblies was not successful. However macrocyclic systems were made by linking two IPI units with two ethoxyethyl or with two ethoxyethoxyethyl units. Also two F-PIP-F units were similarly reacted to give polyether-linked macrocycles. Mono- and bis-prop-2-ynylated IPI derivatives were made but could not be cyclised. Attempts to cyclise ethylenediamine and oxamide based systems were also unsuccessful. The linear and macrocyclic ligands showed calcium selectivity in a study of their metal complexing abilities.

References

1. Part of this work appeared as a preliminary poster in: O. Meth-Cohn, Y. Zegui and J. Hui, Electronic Conference on Current Trends in Organic Chemistry, (ECTOC-1), eds, H. S. Rzepa and J. G. Goodman, Royal Society of Chemistry publications, (CD-ROM), 1995.
2. (a) R. J. Hayward and O. Meth-Cohn, J. Chem. Soc., Perkin Trans. 1, 1975, 212; (b) M. M. Htay and O. Meth-Cohn, Tetrahedron Lett., 1976, 17, 79; (c) M. M. Htay and O. Meth-Cohn, Tetrahedron Lett., 1976, 17, 469.
3. L. J. Kaplan, G. R. Weisman and D. J. Cram, J. Org. Chem., 1979, 44, 2226; D. J. Cram, I. B. Dicker, C. B. Knobler and K. N. Trueblood, J. Am. Chem. Soc., 1982, 104, 6828; R. J. M. Nolte and D. J. Cram, J. Am. Chem. Soc., 1984, 106, 1416; H. E. Katz and D. J. Cram, J. Am. Chem. Soc., 1984, 106, 4977; D. J. Cram, H. E. Katz and I. B. Dicker, J. Am. Chem. Soc., 1984, 106, 4987; D. J. Cram, I. B. Dicker, M. Lauer, C. B. Knobler and K. N. Trueblood, J. Am. Chem. Soc., 1984, 106, 7150; K. M. Doxsee, M. Feigel, K. D. Stewart, J. M. Canary, C. B. Knobler and D. J. Cram, J. Am. Chem. Soc., 1987, 109, 3098; J. Bryant, S. P. Ho, C. B. Knobler and D. J. Cram, J. Am. Chem. Soc., 1990, 112, 5837.
4. E. Weber, M. Piel, H.-J. Buschmann and E. Cleve, Chem. Ber., 1992, 125, 2483.
5. Z. Shi and R. P. Thummel, Tetrahedron Lett., 1995, 36, 2741.
6. S. Kumar, R. Saini and H. Singh, Tetrahedron Lett., 1992, 33, 7937; S. Kumar, R. Saini, N. S. Poonia and H. Singh, Ind. J. Chem., 1995, 34B, 81.
7. M. Rosser, D. Parifer, G. Ferguson, J. F. Gallagher, J. A. K. Howard and D. S. Yufit, J. Chem. Soc., Chem. Commun., 1993, 1267.
8. J. D. Kilburn, A. R. MacKenzie and W. C. Still, J. Am. Chem. Soc., 1988, 110, 1307; R. Liu, P. E. J. Sanderson and W. C. Still, J. Org. Chem., 1990, 56, 5184.
9. J. W. H. Smeets, R. P. Sijbesma, L. van Dalen, A. L. Spek, W. J. J. Smeets and R. J. M. Nolte, J. Org. Chem., 1989, 54, 3710; J. W. H. Smeets, L. van Dalen, V. E. M. Kaats-Richter and R. J. M. Nolte, J. Org. Chem., 1990, 55, 454; R. P. Sijbesma and R. J. M. Nolte, J. Org. Chem., 1991, 56, 3122.
10. H. Quast and U. Nahr, Chem Ber., 1984, 117, 2761.
11. H. R. Kricheldorf and O. Stober, Eur. Polym. J., 1992, 28, 1377.
12. H. Wetter and K. Oertle, Tetrahedron Lett., 1985, 26, 5515.
13. N. A. Puschin and R. V. Mitic, Liebigs Ann. Chem., 1937, 523, 300.
14. J. Tafel and L. Reindl, Chem. Ber., 1901, 34, 3286.
15. C. E. Schweitzer, J. Org. Chem., 1950, 15, 471; A. R. Butler and I. Hussain, J. Chem. Soc., Perkin Trans. 1, 1981, 317.
16. T. Yoshida, N. Kambe, S. Murai and N. Sonoda, Tetrahedron Lett., 1986, 27, 3037; Bull. Chem. Soc. Jpn., 1987, 60, 1793; K. Kondo, S. Yokoyama, N. Miyoshi, S. Murai and N. Sonoda, Angew. Chem., Int. Ed. Engl., 1979, 18, 692.
17. S. G. Davis and A. A. Mortlock, Tetrahedron Lett., 1991, 32, 4791.
18. R. C. Lankemore, C. R. Ganellin and C. J. Theobald, Eur. J. Med. Chem., 1987, 22, 91.
19. J. Bernstein, B. Stearns, E. Shaw and W. A. Lott, J. Am. Chem. Soc., 1947, 69, 1151; P. Buhlmann and W. Simon, Tetrahedron, 1993, 49, 7627.
20. T. Kauffman, J. Legler, E. Ludorff and H. Fischer, Angew. Chem., Int. Ed. Engl., 1972, 11, 846.
21. M. Begtrup, Bull. Soc. Chim. Belg., 1988, 97, 573.
22. B. H. Lipshutz, B. Huff and W. Hagen, Tetrahedron Lett., 1988, 29, 3411.
23. T. P. Johnston, G. S. McCaleb, P. S. Opliger and J. A. Montgomery, J. Med. Chem., 1966, 9, 892.
24. V. Burckhardt, H. Sutter and W. Kundig, GP 829 894/ 1954; (Chem. Abstr., 1958, 52, 11 127e).
25. J. E. B. Ransohoff and H. A. Staab, Tetrahedron Lett., 1985, 26, 6179.
26. A. Lorente, M. Fernandez-Saiz, J.-M. Lehn and J.-P. Vigneron, Tetrahedron Lett., 1995, 36, 8279.
27. M. E. Haeg, B. J. Whitlock and H. W. Whitlock, J. Am. Chem. Soc., 1989, 111, 692.
28. J. Reedijk, T. M. Mulder and J. A. Smit, Inorg. Chim. Acta, 1975, 13, 219.
29. F. Kiriakidou and E. Manessi-Zoupa, Polyhedron, 1996, 15, 1031.
30. E. P. Kyba, R. C. Helgeson, K. Madan, G. W. Gokel, T. L. Tarnowski, S. S. Moore and D. J. Cram, J. Am. Chem. Soc., 1977, 99, 2564.
31. J. M. Timko and D. J. Cram, J. Am. Chem. Soc., 1977, 99, 4207.
32. J. W. H. Smeets, L. van Dalen, V. E. M. Kaats-Richter and R. J. M. Nolte, J. Org. Chem., 1990, 55, 454.
33. D. D. Perrin and W. L. F. Armarego, Purification of Organic Compounds, 3rd edn., Pergamon Press, Oxford, 1988.
34. A. E. Chichibabin, Chem. Ber., 1924, 67, 1172.