銅金屬催化氧化胺、烯、醛三組成之反應物以合成喹啉鹽

簡易檢索 / 詳目顯示

回結果列表

研究生：	賴丞峻 Lai, Cheng-Chun
論文名稱：	銅金屬催化氧化胺、烯、醛三組成之反應物以合成喹啉鹽 Copper-Catalyzed Oxidative Three-Component Reaction of Amines, Alkenes and Aldehydes for the Synthesis of Quinolinium Salts
指導教授：	鄭建鴻 Cheng, Chien-Hong
口試委員:	蔡易州 Tsai, Yi-Chou 謝仁傑 Hsieh, Jen-Chieh
學位類別：	碩士 Master
系所名稱：	理學院 - 化學系 Department of Chemistry
論文出版年：	2019
畢業學年度：	107
語文別：	中文
論文頁數：	93
中文關鍵詞：	喹啉鹽、三組成反應
外文關鍵詞：	Quinolinium Salts, Three-Component Reaction
相關次數：	點閱：2 下載：0
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

喹啉鹽類在生醫製藥方面已展現諸多的應用性，其良好的生物活性持續地被
研究。本篇論文以Povarov 反應為基礎，利用二級胺、烯和聚甲醛作為反應起始
物，在酸的輔助下環化形成四氫喹啉後，銅金屬作為氧化劑合成喹啉鹽類。以催
化量的銅金屬搭配氧氣作為氧化劑，可減少有機或金屬氧化副產物的產生。此外，
烷基喹啉鹽與芳基喹啉鹽均可透過本反應進行合成。

Quinolinium salts have been widely studied due to its important biological activities and show great application in pharmaceuticals and materials recently. In this thesis, we report a new pathway for the synthesis of quinolinium salts based on Povarov reaction. Iminium ion is formed after condensation of secondary amine and aldehyde, followed by cyclization with alkene and oxidation by copper to give the product quinolinium salt. Catalytic amount of copper oxide and the usage of oxygen prevent the waste of organic or inorganic oxidants. In addition, N-methyl and N-phenyl quinolinium salts can both be synthesized via this synthetic strategy.

摘要................................................................................................................................ I
Abstract ......................................................................................................................... II
目錄.............................................................................................................................. III
簡稱對照表................................................................................................................... V
圖目錄.......................................................................................................................... VI
表目錄.......................................................................................................................... VI
式目錄........................................................................................................................ VII
銅金屬催化氧化胺、烯、醛三組成之反應物以合成喹啉鹽.................................... 1
緒論 ................................................................................................................. 1
1 喹啉鹽類之應用................................................................................ 1
2 喹啉鹽類合成文獻回顧 ...................................................................... 3
3 Povarov 反應......................................................................................... 7
研究動機 ....................................................................................................... 10
實驗結果與討論 ........................................................................................... 12
1 以酮和炔的反應條件進行測試 ........................................................ 12
2 金屬催化劑測試 ................................................................................ 13
3 溶劑測試 ............................................................................................ 14
4 空氣與氧氣環境測試 ........................................................................ 15
5 溫度測試 ............................................................................................ 15
6 銅試劑更換 ........................................................................................ 16
7 時間、反應物用量測試 .................................................................... 17
8 末端烯之官能基容忍度測試 ............................................................. 18
9 兩端均有取代基之烯類官能基容忍度測試 .................................... 22
10 二級胺之官能基容忍度測試 .......................................................... 23
11 醛類之官能基容忍度測試 .............................................................. 26
12 克級反應測試 ................................................................................... 28
13 反應機構探討 .................................................................................. 28
結論 ............................................................................................................... 32
實驗部分 ....................................................................................................... 33
1 藥品與儀器 ........................................................................................ 33
2 實驗步驟 ............................................................................................ 35
3 實驗數據 ............................................................................................. 42
參考文獻 ....................................................................................................... 57
附錄一、X-ray 晶體數據 .................................................................................. 60
附錄二、核磁共振光譜 .................................................................................... 67

                                

1. Barlow, R. B.; Himms, J. M. Brit. J. Pharmacol. 1955, 10, 173-174.
2. Collier, H. O. J.; Potter, M. D.; Taylor, E. P. Brit. J. Pharmacol. 1955, 10, 343.
3. Crawford, P. W.; Foye, W. O.; Ryan, M. D.; Kovacic, P. Journal of
Pharmaceutical Sciences 1987, 76, 481-484.
4. (a) Turner, J. A.; Johnson, P. E. Jr. The Journal of Pediatrics 1962, 60, 243-251. (b)
Esumi, H.; Lu, J.; Kurashima, Y.; Hanaoka, T. Cancer Sci. 2004, 95, 685-690. (c)
Ishii, I.; Harada, Y.; Kasahara, T. Front. Oncol. 2012, 2, 137-140. (d) Deng, L.; Lei,
Y.; Liu, R.; Li, J.; Yuan, K.; Li, Y.; Chen, Y.; Liu, Y.; Lu, Y.; Edwards, C. K. III;
Huang, C.; Wei, Y. Cell Death and Disease 2013, 4, 614-623.
5. Leleu, S.; Penhoat, M.; Bouet, A.; Dupas, G.; Papamicaël, C.; Marsais, F.;
Levacher, V. J. Am. Chem. Soc. 2005, 127, 15668-15669.
6. Yamada, Y.; Miyahigashi, T.; Kotani, H.; Ohkubo, K.; Fukuzumi, S. J. Am. Chem.
Soc. 2011, 133, 16136-16145.
7. Wu, W.; Zhan, L.; Ohkubo, K.; Yamada, Y.; Wu, M.; Fukuzumi, S. Journal of
Photochemistry and Photobiology B: Biology 2015, 152, 63-70.
8. Yamada, Y.; Nomura, A.; Miyahigashi, T.; Ohkubo, K.; Fukuzumi, S. J. Phys.
Chem. A 2013, 117, 3751−3760.
9. (a) Kim, J.-S.; Jeong, J.-H.; Yun, H.; Jazbinsek, M.; Kim, J. W.; Rotermund, F.;
Kwon, O.-P. Cryst. Growth Des. 2013, 13, 5085-5091. (b) Li, Z.; Mukhopadhyay,
S.; Jang, S.-H.; Brédas, J.-L.; Jen, A. K.-Y. J. Am. Chem. Soc. 2015, 137,
11920−11923.
10. Sidorchuk, I. I.; Stadniichuk, R. F.; Tishchenko, E. I.; Bordyakovskaya, L. T.
Pharm. Chem. J. 1978, 12, 78-80.
11. (a) Zayas, B.; Beyley, J.; Terron, M.; Cordero, M. Hernandez, W.; Alegría, A. E.;
Cox, O. Toxicology in Vitro 2007, 21, 1155-1164. (b) Colón, I. G.; González, F.
A.; Cordero, M.; Zayas, B.; Velez, C.; Cox, O.; Kumar, A.; Alegría, A. E. Chem.
Res. Toxicol. 2008, 21, 1706-1715.
12. (a) Boateng, C. A.; Eyunni, S. V. K.; Zhu, X. Y.; Etukala, J. R.; Bricker, B. A.;
Ashfaq, M. K.; Jacob, M. R.; Khan, S. I.; Walker, L. A.; Ablordeppey, S. Y.
Bioorg. Med. Chem. 2011, 19, 458-470. (b) Kotani, H.; Ohkubo, K.; Fukuzumi,
S. Faraday Discuss. 2012, 155, 89-102. (c) Motaleb, A.; Bera, A.; Maity, P.
Org. Biomol. Chem. 2018, 16, 5081-5085. (d) Carreon, J. R.; Mahon, K. P. Jr.;
Kelley, S. O. Org. Lett. 2004, 6, 517-519. (e) Wu, C.-K.; Yang, D.-Y. RSC Adv.
2016, 6, 65988-65994. (f) Swinburne, A. N.; Paterson, M. J.; Beeby, A.; Steed,
J. W. Org. Biomol. Chem. 2010, 8, 1010-1016.
13. Pilyugin, G. T.; Gutsulyak, B. M. Russian Chemical Reviews 1963, 32, 167-188.
14. Cox, O.; Jackson, H.; Vargas, V. A.; Báez, A.; Colón, J. I.; González, B. C.; León,
M. D. J. Med. Chem. 1982, 25, 1378-1381.
15. (a) Meth-Cohn, O.; Stanforth, S. P. Comprehensive Organic Synthesis 1991, 2,
777-794. (b) Meth-Cohn, O.; Taylor, D. L. Tetrahedron Letters 1993, 34, 3629-
3632.
16. Meth-Cohn, O.; Taylor, D. L. Tetrahedron 1995, 51, 12869-12882.
17. Mel’nik, M. V.; Turov, A. V.; Novitskii, Z. L.; Stetskiv, A. O.; Bodnarchuk, O. V.;
Ganushchak, N. I. Russian Journal of General Chemistry 2006, 76, 634-637.
18. Chen, W.-C.; Gandeepan, P.; Tsai, C.-H.; Luo, C.-Z.; Rajamalli, P.; Cheng, C.-H.
RSC Adv. 2016, 6, 63390–63397.
19. 陳韋禎 (2017)。銠與銅錯合物之催化環化反應：苯並呋喃與喹啉鹽類合成應
用。國立清華大學化學研究所博士論文，未出版，新竹市。
20. 鄭琳潔 (2018)。銅金屬催化胺、炔、醛氧化環化反應以合成喹啉鹽類。國立
清華大學化學研究所碩士論文，未出版，新竹市。
21. Luo, C.-Z.; Gandeepan, P.; Wu, Y.-C.; Chen, W.-C.; Cheng, C.-H. RSC Adv. 2015,
5, 106012-106018.
22. Kouznetsov, V. V. Tetrahedron 2009, 65, 2721-2750.
23. Shindoh, N.; Tokuyama, H.; Takemoto, Y.; Takasu, K. J. Org. Chem. 2008, 73,
7451-7456.
24. Richter, H.; Mancheño, O. G. Org. Lett. 2011, 13, 6066-6069.
25. Zhang, X.; Xu, X.; Yu, L.; Zhao, Q. Asian J. Org. Chem. 2014, 3, 281-284.
26. Zhang, X.; Xu, X. Chem. Asian J. 2014, 9, 3089-3093.
27. Gao, Q.; Liu, S.; Wu, X.; Wu, A. Org. Lett. 2014, 16, 4582-4585.
28. Gandeepan, P.; Rajamalli, P.; Cheng, C.-H. Asian J. Org. Chem. 2014, 3,
303-308.
29. Zhang, J.-Z.; Tang, Y. Adv. Synth. Catal. 2016, 358, 752-764.
30. Wang, X.; Jang, H.-Y. Bull. Korean Chem. Soc. 2012, 33, 1785-1787.
31. Khalil, N. S. A. M. European Journal of Medicinal Chemistry 2010, 45, 5265-
5277.

簡易檢索 / 詳目顯示

相關論文