臺灣博碩士論文加值系統

芳杯具有孔洞性結構，為分子辨識領域提供一個非常有用的分子設計平台，將芳杯修飾上多個螯合基團輔助抓取分子是我們所感興趣的研究方向。
本論文已經發展出有效地與高產率的1,3-偶極環化加成方法在芳杯上緣或下緣修飾不同的雜環芳香取代基，所生成的isoxazolines與isoxazoles 62–71可藉由開環反應得到雙官能基化合物，如此一來，芳杯分子不僅具有多個螯合基團，並且可藉由芳香雜環分子的螢光性偵測分子辨識行為。
此外，我們利用雙腈氧化物與上緣單丙烯基取代芳杯進行反應，得到非預期中的特殊分子內架橋芳杯75與分子間架橋芳杯76。由控制實驗顯示，作為溶劑的乙醇會大量消耗腈氧化物，而無法得到與腈氧化物進行親電子取代反應產物。
最後，我們利用相當高產率的click條件在芳杯下緣引入高螢光性的香豆素基團，得到化合物85–88，其螢光量子產率高達0.7。藉由三氮唑與香豆素上雜原子的輔助，預期可用於客體分子的螢光辨識系統。

Calixarenes, which are cavity-containing compounds, are very useful molecular platforms in molecular recognition research. There has been a growing interest in modifying calixarenes with two or more binding sites.
We have developed a high yield and convenient method in modifying calixarene with various heterocyclic compounds by 1,3-dipolar cycloaddition reation either on the “lower rim” or on the “upper rim”. The isoxazolines and isoxazoles 62–71 obtained from these reactions are known to be very useful precursors for various bifunctional compounds by ring-opening reactions. Based on this design, the calix[4]arenes not only provide multifunctional chelating sites but also the fluorescence properties from the appended aromatics.
Besides, calix[4]arene with a unique structure 75 was obtained by 1,3-dipolar cycloaddition and electrophilic substitution between bis-dipoles and monodipolarophile. Compound 76 was also isolated from this reaction. Using nitrile oxide 61c react with 2,6-dimethlphenol for comparison, no such an electrophile substitution product can be found because nitrile oxide was consumed by ethanol which served as a solvent.
Finally, Copper (I) catalyzed 1,3-dipolar cycloaddition reactions of 3-azidocoumarin and calix[4]arene bearing propagyl group afforded mono- and bis-1,2,3-triazole substituted calix[4]arenes 85–88, The carbonyl group on the coumarin and the nitrogen atoms on triazole may play an important part in molecular recognitions.

中文摘要 ……………………………………………………….. i
英文摘要 …………………………………………………….. iii
致謝 …………………………………………………….. v
目錄 ……………………………………………………….. vi
圖目錄 ……………………………………………………….. viii
式圖目錄 ……………………………………………………….. xi
表目錄 ……………………………………………………….. xii
附圖目錄 ……………………………………………………….. xiii
第一章 緒論………………………………………………….. 1
1.1 超分子化學簡介…………………………………….. 1
1.2 芳杯簡介…………………………………………….. 2
1.3 芳杯之命名規則…………………………………….. 4
1.4 芳杯之性質與特性………………………………….. 5
1.5 芳杯之合成與衍生化……………………………….. 12
1.6 1,3-偶極環化加成反應……………………………… 21
1.7 含螢光基團芳杯之應用……………………………... 28
1.8 含芳香雜環芳杯之應用…………….……………….. 43
第二章 研究動機…………………………………………….. 49
第三章 結果與討論………………………………………….. 50
3.1 p-tert-Butylcalix[4]arene之合成………………… 50
3.2 芳杯3之合成….………………………...……….. 51
3.3 丙烯基取代芳杯之合成………..……………………. 52
3.4 丙炔基取代芳杯之合成……..……………………… 54
3.5 Hydroximoyl chloride衍生物60c–61c之合成…… 58
3.6 含取代Isoxazoline與Isoxazole芳杯衍生物之合成研究 60
3.7 上緣Thiophene架橋芳杯之合成研究……………… 68
3.8 下緣香豆素取代芳杯之合成研究................. 77
3.9 下緣香豆素取代芳杯與金屬離子錯合之研究....... 84
第四章 結論..........................................91
第五章 實驗部份......................................92
5.1 試藥及測試方法................................92
5.2 實驗步驟及光譜資料............................94
第六章 參考文獻.....................................132
附圖 .............................................141
附錄 .............................................247
簡歷 .............................................250

1. Agre, P; MacKinnon, R. The Nobel Prize in Chemistry 2003 – Information for the Public, 2003 (官方網站：http://nobelprize.org/chemistry/laureates /2003/public.html).
2. Lehn, J.-M. Supramolecular Chemistry–Scope and Perspectives Molecules：Supramolecules, Molecular Devices, Nobel Lecture, 1987. (官方網站：http://nobelprize.org/chemistry/laureates/1987/lehn-lecture.html).
3. Gutsche, C. D. Acc. Chem. Res. 1983, 16, 161.
4. (a) Zinke, A.; Ziegler, E. Ber. 1944, 77, 264. (b) Cornforth, J. W.; D’Arcy Hart, P.; Nicholles, G. A.; Rees, R. J. W.; Stock, J. A. Br. J. Pharmacol. 1955, 10, 73. (c) Gutsche, C. D. Calixarenes; The Royal Society of Chemistry: Cambridge, 1992. (d) Gutsche, C. D. Calixarenes Revisited; The Royal Society of Chemistry: Cambridge, 1998.
5. Munch, J. H. Markromol. Chem. 1977, 178, 69.
6. Arduini, A.; Pochini, A.; Reverberi, S.; Ungaro, R. J. Chem. Soc., Perkin Trans. 1 1987, 2297.
7. (a) Gutsche, C. D.; Pagoria, P. F. J. Org. Chem. 1985, 50, 5795. (b) Gutsche, C. D. ; Alam, I. Tetrahedron 1988, 44, 4689.
8. Böhmer, V.; Schade, E.; Vogt, W. Markromol. Chem. 1984, 5, 221.
9. Mandolini, L.; Ungaro, R. Calixarenes in Action, Imperial College Press: London, 2000.
10. (a) Böhmer, V. Angew. Chem. Int. Ed. Engl. 1995, 34, 713. (b) Araki, K.; Shinkai, S.; Matsuda, T. Chem. Lett. 1989, 581. (c) Shinkai, S.; Araki, K.; Matsuda, T.; Manabe, O. Bull. Chem. Soc. Jpn. 1989, 3856.
11. Gutsche, C. D.; Dhawan, B.; Levine, J. A.; No, K. H.; Bauer, L. J. Tetrahedron 1983, 39, 409.
12. Bocchi, V.; Foina, D.; Pochini, A.; Ungaro, R. Tetrahedron 1982, 38, 373.
13. Shinkai, S.; Arkai, K.; Iwamoto, K. J. Org. Chem. 1991, 56, 4955.
14. Shimizu, S.; Moriyama, A.; Kito, K.; Sasaki, Y. J. Org. Chem. 2002, 68, 2187.
15. de Namor, A. F. D.; Cleverley, R. M.; Zepata-Ormachea, M. L. Chem. Rev. 1998, 98, 2495.
16. Dhawan, B.; Chen, S.-I.; Gutsche, C. D. Makromol. Chem. 1987, 188, 921.
17. Iqbal, M.; Mangiafico, T.; Gutsche, C. D. Tetrahedron, 1987, 43, 4917.
18. Gutsche, C. D.; Reddy, P. A. J. Org. Chem. 1991, 56, 4783.
19. de Namor, A. F. D.; Chahine, S.; Kowalska, D.; Castellano, E. E.; Piros, O. E. J. Am. Chem. Soc. 2002, 124, 12824.
20. Scheerder, J.; Fochi, M.; Engbersen, J. F. J.; Reinhoudt, D, N. J. Org. Chem. 1994, 59, 7815.
21. Meunier, S.; Roy, R. Tetrahedron Lett. 1996, 37, 5469.
22. Gonzcilez, J. J.; Nieto, P. M.; Prados, P.; Echavarren, A. M.; de Mendoza, J. Org. Chem. 1995, 60, 7419.
23. (a) Gibbs, C. G.; Gutsche, C. D. J. Am. Chem. Soc. 1993, 115, 5338. (b) Gibbs, C. G.; Sujeeth, P. K.; Rogers, J. S.; Stanley, G. G.; Krawiec, M.; Watson, W. H.; Gutsche, C. D. J. Org. Chem. 1995, 60, 8394.
24. (a) Shinkai, S.; Arkai, K.; Shibata, K.; Shinbata, J.; Manabe, O. J. Chem. Soc., Perkin Trans. 1 1990, 3333. (b) Momura, E.; Taniguchi, H.; Tamura, S. Chem. Lett. 1989, 1125. (c) Morita, Y.; Agawa, T.; Nomura, E.; Taniguchi, H. J. Org. Chem. 1992, 57, 3658. (d) Yeh, M.-L.; Fang, F.-S.; Chen, S.-L.; Liu, W.-C.; Lin, L.-G. J. Org. Chem. 1994, 59, 754.
25. (a) Shinkai, S.; Mori, S.; Tsubaki, T.; Sone, T.; Manabe, O. Tetrahedron Lett. 1984, 25, 5315. (b) Shinkai, S.; Arkai, K.; Tsubaki, T.; Ariumura, T.; Manabe, O. J. Chem. Soc., Perkin Trans. 1 1987, 2297.
26. (a) Kovalev, V.; Shokova, E.; Khomich, A.; Luzikov, Y. New. J. Chem. 1996, 20, 483. (b) Kovalev, V.; Shokova, E.; Khomich, A.; Luzikov, Y. Synthesis 1998, 1003.
27. (a) Huang, Z.-T.; Wang, G.-Q. J. Chem. Soc., Perkin Trans. 1 1993, 167. (b) Huang, Z.-T.; Wang, G.-Q. Chem. Ber. 1994, 127, 519.
28. (a) Arduini, A.; Fanni, S.; Manfredi, G.; Pochini, A.; Ungaro, R.; Sicuri, A. R.; Ugozzoli, F. J. Org. Chem. 1995, 60, 1448. (b) Arora, V.; Chawla, H. M.; Santra, A. Tetrahedron 2002, 58, 5591. (c) Lewin, A. H.; Parker, S. R.; Fleming, N. B.; Carroll, F. I. Org. Prep. Proced. Int. 1978, 10, 201.
29. Kenis, P. J. A.; Noordman, O. F. J.; Hulst, N. F. V.; Engbersen, J. F. J.; Reinhoudt, D. N. Chem. Eur. J. 1997, 9, 596.
30. Larsen, M.; Jorgensen, M. J. Org. Chem. 1997, 62, 4171.
31. (a) Alfieri, G.; Dradi, E.; Pochini, A.; Ungaro, R.; Andreetti, G. D. J. Chem. Soc., Chem. Commun. 1983, 1075. (b) Ungaro, R.; Pochini, A.; Andreetti, G. D. J. Inclusion Phenom. 1984, 2, 199. (c) Beer, P. D.; Keefe, A. D.; J. Inclusion Phenom. 1987, 5, 499. (d) Reinhoudt, D. N.; Dijkstra, P. J.; A. in’t Veld, P. J.; Bugge, K. E.; Harkema, S.; Ungaro, R.; Ghidini, E. J. Am. Chem. Soc. 1987, 109, 4761.
32. (a) Arduini, A.; Casnati, A.; Dodi, L.; Pochini, A.; Ungaro, R. J. Chem. Soc., Chem. Commun. 1990, 1597. (b) Carmeron, B. R.; Loed, S. J. Chem. Commun. 1996, 2003. (c) Rudkevich, D. M.; Verboom, W.; Reinhoudt, D. N. J. Org. Chem. 1994, 59, 3683.
33. (a) McKervey, M. A.; Pitatch, M. Chem. Commun. 1996, 1689. (b) Arimura, T.; Brown, C. T.; Springs, S. T.; Sessler, J. L. Chem. Commun. 1996, 2293. (c) McKervey, A. M.; Owens, M.; Schulten, H.-R.; Vogt, W.; Böhmer, V. Angew. Chem., Int. Ed. 1990, 28, 280.
34. Francisco, S. G.; Antonio, T. P.; Claudio, S. B. Eur. J. Org. Chem. 2000, 21, 3587.
35. Jan, B.; Pavel, L.; Ivan, S.; Veronika, M.; Jan, S.; Ivana, C. Tetrahedron Lett. 2002, 43, 2857.
36. (a) Kraft, D.; van Loon, J.-D.; Owens, M.; Verboom, W.; Vogt, W.; McKervey, A. M.; Böhmer, V.; Reinhoudt, D. N. Tetrahedron Lett. 1990, 31, 4941. (b) Asfari, Z.; Weiss, J.; Pappalardo, S.; Vicens, J. Pure Appl. Chem. 1993, 65, 585.
37. Arduini, A.; Pochini, A.; Secchi, A. Eur. J. Org. Chem. 2000, 12, 2325.
38. Hwang G. T.; Kim B. H. Tetrahedron Lett. 2000, 41, 5917.
39. (a) Liu, J. M.; Zheng, Y. S.; Zhung, Q. Y.; Xie, J. Wang, M. X.; Huang, Z. T. Tetrahedron 2002, 58, 3729. (b) Zheng, Y. S.; Huang, Z. T. Tetrahedron Lett. 1998, 39, 5811.
40. (a)Padwa, A.; William, H. P., The Chemistry of Heterocyclic Compound, Vol 59: Synthetic Applications of 1,3-dipolar Cycloaddition Toward Heterocycles and Natural Products; Wiley: New York, 2002. (b) Padwa, A., 1,3-Dipolar Cycloaddition Chemistry; Wiley: New York, 1984.
41. Weygand, C.; Bauer, E. Justus Liebigs Ann. Chem. 1927, 459, 123.
42. Quilico, A.; Speroni, G. Gazz. Chem. Ital. 1946, 76, 148.
43. (a) Huisgen, R. Proc. Chem. Soc. 1961, 357. (b) Houk, K. N. Acc. Chem. Res. 1975, 8, 361.
44. Kozikowski, A. P. Acc. Chem. Res. 1984, 17, 410.
45. Liu, K.-C.; Shelton, B. R.; Howe, R. K. J. Org. Chem. 1980, 45, 3916.
46. (a) Calvo, L. A.; González-Nogal, A. M.; González-Ortega, A.; Sañudo M. C. Tetrahedron Lett. 2001, 42, 8981. (b) Auricchio, S.; Bini, A.; Pastormerlo, E.; Truscello, M. Tetrahedron 1997, 53, 10911. (c) Fan, X.; Zhang, Y. Tetrahedron Lett. 2002, 43, 7001. (d) Li, C. S.; Lacasse, E. Tetrahedron Lett. 2002, 43, 3565. (e) Churykau, D. H.; Zinovich, V. G.; Kulinkovich, O. G. Synlett. 2004, 11, 1949.
47. (a) Ullman, E. F.; Singh, B. J. Am. Chem. Soc. 1966, 88, 1844. (b) Sauers, R. R.; Van Arnum, S. D. Tetrahedron Lett. 1987, 28, 5797.
48. Dalvie, D. K.; Kalgutkar, A. S.; Khojasteh-Bakht, S. C.; Obach, R. S.; O'Donnell, J. P. Chem. Res. Toxicol. 2002, 15, 269.
49. Zhang, Q.; Pang, W. L.; Chen, H.; Cherrington, J.; Lipson, K.; Antonian, L.; Shawver, L. K. J. Pharm. Biomed. Anal. 2002, 28, 701.
50. Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem. Int. Ed. 2001, 40, 2004.
51. Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem. Int. Ed. 2002, 41, 2596.
52. Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.; Noodleman, L.; Sharpless, K. B.; Fokin, V. V. J. Am. Chem. Soc. 2005, 127, 210.
53. Feldman, A. K.; Colasson, B.; Fokin, V. V. Org. Lett. 2004, 6, 3897.
54. Appukkuttan, P.; Dehaen, W.; Fokin, V. V.; Van der Eycken, E.; Org. Lett. 2004, 6, 4223.
55. Saxon, E.; Bertozzi, C. R. Science 2000, 287, 2007.
56. (a) Wamhoff, H. In Comprehensive Heterocyclic Chemistry; Vol. 5 Katritzky, A. R.; Rees, C. W., Ed.; Pergamon: Oxford, 1984. (b) Lee, L. V.; Mitchell, M. L.; Huang, S. J.; Fokin, V. V.; Sharpless, K. B.; Wong, C. H. J. Am. Chem. Soc. 2003, 125, 9588.
57. Löber, S.; Rodriguez-Loaiza, P.; Gmeiner, P.; Org. Lett. 2003, 5, 1753.
58. Sivakumar, K.; Xie, F.; Cash, B. M.; Long, S.; Barnhill, H. N.; Wang, Q.
Org. Lett. 2004, 6, 4603.
59. Valeur, B.; Leray, I. Coord. Chem. Rev. 2000, 205, 3-40.
60. Valeur, B. Molecular Fluorescence: Principles and Applications; Wiley- VCH: Weinheim, 2001.
61. Bu, J. H.; Zheng, Q. Y.; Chen, C. F.; Huang, Z. T. Org. Lett. 2004, 6, 3301.
62. (a) Leray, I.; Valeur, B. Chem. Commun. 1999, 795. (b) Narita, M.; Higuchi, Y.; Hamada, F.; Kumagai, H. Tetrahedron Lett. 1998, 39, 8687.
63. De silva, A. P.; Fox, D. B.; Huxley, A. J. M.; McCoy, C. P. Chem. Rev. 1997, 97, 1515.
64. (a) Kim, S. K.; Lee, S. H.; Lee, J. Y.; Lee, J. Y.; Bartsch, R. A.; Kim, J. S.
J. Am. Chem. Soc. 2004, 126, 16499. (b) Yang, J. S.; Lin, C. S.; Hwang, C. Y. Org. Lett. 2001, 3, 889.
65. Pailleret, A.; Arrigan, D. W. M.; Browne, J, K.; Mckervey, M. A. J. Mater. Chem. 2002, 12, 2665.
66. (a) Sessler, J. L.; An, D.; Cho, W.-S.; Lynch, V.; Yoon, D. W.; Hong, S. J.;