臺灣博碩士論文加值系統

本論文主要研究方向為固有掌性偶氮冠醚雙芳杯之合成及其對掌性胺基醇類客體的辨識能力的主客化學。
首先，在NaH做為鹼及DMF作為溶劑的條件下，能以高選擇性合成出對位-鄰位冠醚雙橋聯的雙芳杯化合物7b，作為固有掌性芳杯的前驅物，再修飾上酸根及偶氮基團合成固有掌性化合物12b。將外消旋主體化合物 (+/-)-12b與客體胺基醇類分子進行紫外-可見光初步篩選，發現主體只有對phenyl alaninol (G1)才有紫外-可見光光譜上明顯吸收波長的變化，由400 nm 紅位移到575 nm。
在採用掌性管柱的HPLC成功分離出 (+)-12b與 (-)-12b後，分別對鏡像異構物客體 (R)-G1與 (S)-G1進行紫外-可見光滴定實驗以求得錯合常數Ka。從結果得知 (+)-12b與 (S)-G1的錯合常數較大 (Ka = 557 M-1)，與 (R)-G1的錯合常數則較小 (Ka = 159 M-1)，掌性辨識能力之比值Ka(S) / Ka(R) = 3.84。
將化合物 (+)-12b與 (-)-12b分別對鏡像異構物客體 (R)-G1與 (S)-G1進行NMR滴定實驗，從訊號分裂不同的結果可以得知錯合物 (+)-12b-(R)-G1與 (+)-12b-(S)-G1彼此為非鏡像異構物。
化合物12b與客體的錯合模式主要有三種作用力：(1) 加入G1時，12b的酸根會將G1的-NH2質子化，使其變成帶正電的-NH3+，如此一來和12b的冠醚就可產生靜電力；(2) 12b的酸根與G1的羥基之間可有氫鍵作用力；(3) 12b下緣的掌性芳杯所提供的立體障礙會因具掌性的G1的旋光性而有不同大小的立體阻礙排斥力。

The research goal of this thesis is the synthesis of inherently chiral azobiscalix[8]crown and its chiral recogonition toward aminoalcohols.
First, in the condition of NaH as a base and DMF as a solvent, we could obtain 1,3-to-1,2 double bridged biscalix[4]arene compound 7b in high selectivity, which is a good precursor for inherently chiral calix[4]raene. After acidification and adding diazo functional group on 7b, we could obtain inherently chiral compound 12b in 8% yield. UV-vis screening experiment was carried out by adding aminoalcohol compounds to racemic (+/-)-12b. The results showed that only phenyl alaninol, G1, showed red shift in its absorption spectra from 400 nm to 575 nm.
Chiral HPLC column was applied in order to separate (+)-12b and (-)-12b. After separation, UV-vis titration experiments were carried out by adding enatiomer (R)-G1 and (S)-G1 to solution of CHCl3 (+)-12b and (-)-12b, respectively, to obtain corresponding constants Ka. The results show that (+)-12b has a bigger binding constant with (S)-G1 (Ka = 557 M-1) and smaller binding constant with (R)-G1 (Ka = 159 M-1). The chiral recognition ratio of Ka(S) / Ka(R) is 3.84.
NMR titration experiments were carried out by adding enatiomer (R)-G1 and (S)-G1 to (+)-12b and (-)-12b respectively. We could recognize that complex (+)-12b-(R)-G1 and (+)-12b-(S)-G1 are diastereomers from their different NMR signals splittings.

摘要 .................................................................................................................. i
Abstract ........................................................................................................... iii
圖目錄 ................................................................................................................ viii
表目錄 ...................................................................................................................... xiv
附圖目錄...................................................................................................................... xv
第一章 緒論 ............................................................................................................... 1
1.1 超分子化學 ................................................................................................... 1
1.2 掌性辨識 ....................................................................................................... 2
1.3 芳杯簡介 ....................................................................................................... 5
1.3.1 芳杯的修飾 ................................................................................................... 7
1.4 冠醚 ............................................................................................................... 9
1.4.1 冠醚在芳杯上的修飾 ................................................................................. 10
1.5 發色感應器 ................................................................................................. 13
1.5.1 偶氮化合物在芳杯上的修飾 ..................................................................... 15
1.6 固有掌性芳杯 (Inherently chiral calix[4]arene) ........................................ 15
1.7 文獻回顧 ..................................................................................................... 19
1.8 研究動機與目的 ......................................................................................... 27
第二章 結果與討論 ................................................................................................. 29
2.2 單對甲苯磺醯基取代三甘醇化合物1b之合成28 ................................... 33
2.2.1 化合物1b之光譜與結構鑑定 ................................................................... 34
2.3 單對甲苯磺醯基取代-單吡喃保護三甘醇2b化合物之合成28 .............. 35
2.4 叔丁基芳杯下緣對位雙丙醚基取代化合物3b之合成29 ....................... 35
2.4.1 化合物3b之1H NMR光譜與結構鑑定 .................................................. 36
vi
2.5 芳杯下緣對位雙丙醚基-雙聚乙醇化合物5b之合成24 .......................... 37
2.6 下緣對位雙丙醚基-雙聚乙二醇對甲基苯磺酸化合物6b之合成24 ...... 38
2.6.1 化合物6b之1H NMR光譜與結構鑑定 .................................................. 39
2.7 下緣對位-鄰位冠醚雙橋聯雙芳杯冠醚化合物7b之合成 ..................... 40
2.7.1 化合物7b之1H NMR光譜與結構鑑定 .................................................. 42
2.7.2 化合物7b之X光繞射單晶結構分析 ...................................................... 44
2.8 下緣修飾酯基對位-鄰位冠醚橋連雙芳杯冠醚化合物 ()-10b之合成 45
2.8.1 化合物 ()-10b之1H NMR光譜與結構鑑定 ......................................... 46
2.9 對硝基苯四氟硼酸重氮鹽之合成30 ......................................................... 48
2.10 下緣修飾雙偶氮對位-鄰位冠醚橋連雙芳杯冠醚化合物9b之合成 ..... 49
2.10.1 化合物9b之1H NMR光譜與結構鑑定 .................................................. 50
2.10.2 化合物9b之X光繞射單晶結構分析 ...................................................... 51
2.11 下緣修飾偶氮、酯基對位-鄰位冠醚橋連雙芳杯冠醚化合物 ()-11b之合成 ............................................................................................................. 52
2.11.1 化合物 ()-11b之1H NMR光譜與結構鑑定 ......................................... 53
2.12 下緣修飾偶氮、酸基對位-鄰位冠醚橋連雙芳杯冠醚化合物 ()-12b之合成 ............................................................................................................. 54
2.12.1 化合物 ()-12b之1H NMR光譜與結構鑑定 ......................................... 55
2.13 下緣修飾偶氮、1,1-聯二萘酚酯基對位-鄰位冠醚橋連雙芳杯冠醚化合物13b之合成 .................................................................................................. 57 2.14 高效液相色譜分析儀之使用 ..................................................................... 58
2.16 質譜分析 ..................................................................................................... 62
2.17 外消旋偶氮冠醚雙芳杯對客體感測之研究 ............................................. 62
2.18 偶氮冠醚掌性雙芳杯()-12b對掌性客體感測之研究 ............................ 67
vii
第三章 結論 ............................................................................................................. 80
第四章 實驗部分 ..................................................................................................... 82
5.1 試藥級測試方法 ......................................................................................... 82
5.2 實驗步驟及光譜資料 ................................................................................. 85
第五章 參考資料 ..................................................................................................... 99
第六章 附圖部分 ................................................................................................... 103
7.1 1H NMR, 13C NMR光譜圖及質譜圖 .................................................... 103
7.2 晶體結構與參數 ....................................................................................... 140
簡歷 ..................................................................................................................... 178

1. Fabbrizzi, L; Poggi, A. Chem. Soc. Rev. 1995, 24, 197.
2. Easson, E. H.; Stedman, E. Biochem. J. 1933, 27, 1257.
3. Gutch, C.D.; Muthukrishnan, R. J. Org. Chem. 1978, 43, 4905.
4. Jiang, P.-Z.; Chung, W.-S., The Chinese Chem. Soc. 2004, 62, 13.
5. (a) Mandolini, L.; Ungaro, R.; Calixarene in Action, Imperial College Press: London; 2000. (b) Jaime, C.; de Mndoza, J.; Pardos, P.; Nieto, P. M.; Sanchez, C. J. Org. Chem. 1991, 56, 3372.
6. (a) Gutsche, C. D.; Dhawan, B.; Levine, J. A.; No, K. H.; Bauer, L. J. Tetrahedron 1983, 39, 409. (b) Bocchi, V.; Foina, S.; Pochini, A.; Ungaro, R. Tetrahedron 1982, 38, 373.
7. (a) Iwamoto, K.; Araki, K.; Shinkai, S. J. Org. Chem. 1991, 56, 4955. (b) Araki, K.; Iwamoto, K.; Shinkai, S.; Matuda, T. Chem. Lett. 1989,1747. (c) Iwamoto, K.; Araki, K.; Shinkai, S. Tetrahedron 1991, 47, 4325.
8. Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 2495.
9. Gokel, G. W.; Leevy, W. M.; Weber, M. E. Chem. Rev. 2004, 104, 2723.
10. Lovely, A. E.; Wenzel, T. J. Org. Lett. 2006, 8, 2823.
11. Yamamoto, H.; Sakaki, T.; Shinkai. S. Chem. Lett. 1994, 469
12. Araki, K.; Iwamoto, K.; Shigematsu, S.; Shinkai, S. Chem. Lett. 1992, 1095.
13. (a) Kim, J. S.; Lee, S. J.; Jung, J. H.; Hwang, I. C.; Singh, N. J.; Kim,
101
S. K.; Lee, S. H.; Kim, H. J.; Keum, C. S.; Lee, J. W.; Kim, K. S. Chem. Eur. J. 2007, 13, 3082. (b) Kao, T.-L.; Wang, C.-C.; Pan, Y.-T.; Shiao, Y.-J.; Yen, J.-Y.; Shu, C.-M.; Lee, G.-H.; Peng, S.-M.; Chung, W.-S. J. Org. Chem. 2005, 70, 2912. (c) Ho, I.-T.; Lee, G.-H.; Chung, W.-C. J. Org. Chem. 2007, 72, 2434. (d) Chang ,K.-C.; Su, I.-H.; Lee, G.-H.; Chung, W.-S. Tetrahedron Lett. 2007, 48, 7274.
14. Kim, J. Y.; Kim, G.; Kim, C. R.; Lee, S. H.; Lee, J. H.; Kim, J. S. J. Org. Chem. 2003, 68, 1993
15. 何怡婷，偶氮類及自組裝類calix[4]arenes之合成研究與前者的金屬離子感測研究，國立交通大學，碩士論文，2005年。
16. Kubo, Y.; Maeda, S.; Tokita, S.; Kubo, M. Nature 1996, 382, 8.
17. Zheng, Y.-S.; Luo, J. J. Incl Phenom Macro. 2011, 7135.
18. No, K. H.; Gutsche, C. D. J. Org. Chem. 1982, 47, 2713.
19. Böhmer, V.; Kraft, D.; Tabatabai, M. J. Inclusion Phenom. Mol.
Recognit. Chem. 1994, 19, 17.
20. Iwamoto, K.; Shimizu, H.; Arali, K.; Shinkai, S. J. Am. Chem. Soc. 1993, 115, 3997.
21. Cort, A. D.; Mandolini, L.; Pasquini, C.; Schiaffino, L. New J. Chem. 2004, 28, 1198.
22. Tanaka, K.; Okada, T.; Toda, F. Angew. Chem. Int., Ed. 1993, 32, 1147.
23. Luo, J.; Zheng, Q.-Y.; Chen, C.-F.; Huang, Z.-T. Tetrahedron 2005, 61, 8517.
24. Luo, J.; Shen, L-C.; Chung, W.-S. J. Org. Chem. 2010, 75, 464.
25. Li, S-Z.; Shi, J.; Yang, K.; Luo, J. Tetrahedron 2012, 68, 8557.
102
26. (a) Narumi, F.; Hattori, T.; Matsumura, N.; Onodera, T.; Katagiri, H.; Kabuto, C.; Kameyama, H.; Miyano, S. Tetrahedron 2004, 60, 7827; (b) Shirakawa, S.; Moriyama, A.; Shimizu, S. Org. Lett. 2007, 9, 3117; (c) Kliachyna, M. A.; Yesypenko, O. A.; Pirozhenko, V. V.; Shishkina, S. V.; Shishkin, O. V.; Boyko, V. I.; Kalchenko, V. I. Tetrahedron, 2009, 65, 7085.
27. 靳斯羽，偶氮冠醚橋聯雙芳杯之合成及其對胺與金屬離子之顏色感測，國立交通大學，碩士論文，2012年。
28. (a) Ameijde, J.; Liskamp, R. M. J. Org. Biomol. Chem. 2003, 1,26612669. (b) Loiseau, F. A.; Hii, K. K.; Hill, A. M. J. Org. Chem. 2004, 69, 639.
29. Pomecko, R.; Asfai, Z.; Hubscher-Bruder, N.; Bochenska, M.; Arnaud-Neu, F. Supramol. Chem. 2010, 22, 275.
30. Shinkai, S.; Aeaki, K.; Shibata, J.; Tsugawa, D.; Manbe, O. J. Chem. Soc. Perkin Trans 1 1990, 3333.
31. Späth, A.; König, B. Beilstein J. Org. Chem. 2010, 6, 32.
32. Salorinne, K.; Nissinen, M. J. Incl. Phenom. Macrocycl Chem. 2008, 61, 11.
33. Li, S-Z.; Yang, K.; Liu, H-B.; Xia, Y-X.; Zhu, R-X.; Luo, J.; Wan, Q. Tetrahedron Lett. 2013, 54, 5901.
34. (a) Fasman, G. D. In Circular Dichroism and the Conformation-al Analysis of Biomolecules, Plenum Press: New York, 1996; pp3. (b) Rodger, A.; Nordén, B. In Circular Dichroism and LinearDichroism, Oxford University Press, Oxford: UK, 1997.
35. 吳偉新，芳杯冠醚修飾聯二萘酚衍生物之合成與其對胺基醇之掌
103
性辨識研究，國立交通大學，碩士論文，2010年
36. Benesi, H. A.; Hildebrand, J. H. J. Am. Chem. Soc. 1949, 71,
2703.