臺灣博碩士論文加值系統

本研究使用2-醯胺萘醌2a和三級胺做為起始物，和金屬鈀化合物在空氣下進行一鍋化反應，產生吲哚苯醌衍生物，產率都有80%左右，並且得到其中之一產物3c的晶體結構。推測反應是透過金屬鈀化合物先將三級胺活化，使三級胺上的取代基接上2-醯胺萘醌並在脫去氮後進行環化反應，產生吲哚苯醌。最後根據優選條件推出可行的反應機制。
接著也嘗試使用二級胺和一級胺做為反應物，在相同的條件下進行反應，發現當反應物是一級胺且胺的取代基立體障礙小的時候，產物為咪唑苯醌；立體障礙大時為胺基苯醌。而當反應物是二級胺時，主產物是吲哚苯醌並且產率和胺類取代基的立體障礙大小有關，立體障礙越小時，推測會有胺基化苯醌的副產物產生，因此目標產物的產率較低。
另外，也使用三級磷來做為反應物，在相同條件下進行反應，得到的產物則為一種有類似苯醌結構且含有碳-磷雙鍵的ylide(葉立德或鎓內鹽)。

1-H-Benz[f]indole-4,9-diones 3 were prepared in good yields by treating N-(1,4-dioxo-1,4-dihydronaphthalen-2-yl)acetamide 2a with tertiary amines and using Pd(OAc)2 as the catalyst precursor in one-pot reactions and the structure of 3c was determined by single crystal X-ray diffraction methods.
As revealed from the structure of 3c, the transition metal complex Pd(OAc)2 indeed catalyzed amines and 2a, which led to the formation of pyrrole through cyclization processes by fusing to the former napthoquinone framework. A mechanism was proposed after screening some relevant reaction conditions.
Thereafter, similar reactions were carried out by employing primary and secondary amines as the amine sources. When primary amines are used as the reactants, the products will be either imidazolequinones or aminoquinones depending on the extent of the steric hindrance of amines. When secondary amines are used as the reactants, the products will be either indolequinone or aminoquinones again depending on the extent of the steric hindrance of amines.
In addition, similar reactions were carried out by replacing tertiary amines with tertiary phosphines which led to the formation of ylide-like derivatives instead.

目錄

摘要 i
Abstract ii
目錄 iii
Scheme　目錄 v
Figure　目錄 vii
Table　目錄 viii
第一章　序論 1
第一節　Indole-4,7-quinone簡介 2
第二節　C-H鍵活化反應(C-H functionalization reaction)簡介 6
第三節　Quinone上C-H鍵活化反應簡介 8
第四節　研究方向 12
第二章　實驗 15
第一節　儀器與設備 16
第二節　藥品 19
第三節　合成與鑑定 21


第三章　結果與討論 32
第一節　Amido-substituted napthoquinone與三級胺的反應 33
第二節　Amido-substituted napthoquinone與一級胺的反應 47
第三節　Amido-substituted napthoquinone與二級胺的反應 51
第四節　Amido-substituted napthoquinone與三級磷的反應 53
第四章　結論 56
第五章　參考文獻 57
第六章　附錄 64
第一節　光譜數據 65
第二節　晶體數據 93

1.Thosmson, R. H. Pharm. Weekbl. Sci., 1991, 13, 70-73.
2.Patai, S.; Rappaport, Z. The Chemistry of Quinonoid Compounds, Vol II, Wiley: New York, 1988.
3.Koyama, J. Recent Pat. Anti-Infect. Drug Discovery, 2006, 1, 113-125.
4.Brien, J. O’P. Chem. Biol. Interact., 1991, 80, 1-41.
5.Dowd, P.; Zheng, Z. B. Proc. Natl. Acad. Sci., 1995, 92, 8171-8175.
6.(a) Thomson, R. H. Naturally Occurring Quinones, 2nd ed.; Academic Press: London and New York, 1971. (b) Thomson, R. H. Naturally Occurring Quinones III: Recent Advances, 3rd ed.; Chapman and Hall: London and New York, 1987. (c) Sharma, P. S.; Pietrzyk-Le, A.; D’Souza, F.; Kutner, W. Anal. Bioanal. Chem. 2012, 402, 3177-3204. (d) Furstner, A. Angew. Chem., Int. Ed. 2003, 42, 3582-3603. (e) Ryu, C.-K.; Lee, J. Y.; Jeong, S. H.; Nho, J.-H. Bioorg. Med. Chem. Lett. 2009, 19, 146-148. (f) Ryu, C.-K.; Yoon, J. H.; Song, A. L.; Im, H. A.; Kim, J. Y.; Kim, A. Bioorg. Med. Chem. Lett. 2012, 22, 497-499. (g) Shchekotikhin, A. E.; Glazunova, V. A.; Dezhenkova, L. G.; Kaluzhny, D. N.; Luzikov, Y. N.; Buyanov, V. N.; Treshalina, H. M.; Lesnaya, N. A.; Romanenko, V. I.; Balzarini, J.; Agama, K.; Pommier, Y.; Shtil, A. A.; Preobrazhenskaya, M. N. Eur. J. Med. Chem. 2014, 86, 797-805. (h) NadjiBoukrouche, A. R.; On, S.; Khoumeri, O.; Terme, T.; Vanelle, P. Tetrahedron Lett. 2015, 56, 2272-2275. (i) Guo, S.; Chen, B.; Guo, X.; Zhang, G.; Yu, Y. Tetrahedron, 2015, 71, 9371-9375. (j) Gach, K.; Modranka, J.; Szymanski, J.; Pomorska, D.; Krajewska, U.; Mirowski, M.; Janecki, T.; Janecka, A. Eur. J. Med. Chem. 2016, 120, 51-63.
7.(a) Krapcho, A. P.; Waterhouse, D. J. Heterocycles, 1999, 51, 737-749. (b) Okunade, A. L.; Clark, A. M.; Hufford, C. D.; Oguntimein, B. O. Planta Med. 1999, 65, 447-448. (c) Nok, A. J. Cell Biochem. Funct. 2002, 20, 205-212.
8.(a) Arsenault, G. P. Tetrahedron Lett. 1965, 45, 4033-4037. (b) Steyn, P. S.; Wessels, P. L.; Marasas, W. O. F. Tetrahedron, 1979, 35, 1551-1555.
9.(a) Martin, T.; Moody, C. J. J. Chem. Soc., Perkin Trans. 1, 1988, 235-240. (b) Matsuo, K.; Ishida, S. Chem. Expr. 1993, 8, 321-324. (c) Moody, C. J.; Swann, E. Tetrahedron Lett. 1993, 34, 1987-1988. (d) Matsuo, K.; Ishida, S. Chem. Pharm. Bull. 1994, 42, 1325-1327. (e) Hagiwara, H.; Choshi, T.; Fujimoto, H.; Sugino, E.; Hibino, S. Chem. Pharm. Bull. 1998, 46, 1948-1949. (f) Hagiwara, H.; Choshi, T.; Nobuhiro, J.; Fujimoto, H.; Hibino, S. Chem. Pharm. Bull. 2001, 49, 881-886. (g) Sofiyev, V.; Lumb, J.-P.; Volgraf, M.; Trauner, D. Chem.-Eur. J. 2012, 18, 4999- 5005.
10.(a)Lee, E.-J.; Lee, H.-J.; Park, H. J.; Min, H.-Y.; Suh, M.-E.; Chung, H.-J.; Lee, S. K. Bioorg. Med. Chem. Lett. 2004, 14, 5175-5178. (b) Park, H. J.; Lee, H.-J.; Min, H.-Y.; Chung, H.-J.; Suh, M. S.; Park-Choo, H.-Y.; Kim, C.; Kim, H. J.; Seo, E.-K.; Lee, S. K. Eur. J. Pharmacol. 2005, 527, 31-36.
11.(a) Martin, T.; Moody, C. J. J. Chem. Soc., Perkin Trans. 1, 1988, 235-240. (b) Matsuo, K.; Ishida, S. Chem. Express, 1993, 8, 321-324. (c) Matsuo, K.; Ishida, S. Chem. Pharm. Bull. 1994, 42, 1325-1327. (d) Hagiwara, H.; Choshi, T.; Fujimoto, H.; Sugino, E.; Hibino, S. Chem. Pharm. Bull. 1998, 46, 1948-1949. (e) Hagiwara, H.; Choshi, T.; Nobuhiro, J.; Fujimoto, H.; Hibino, S. Chem. Pharm. Bull. 2001, 49, 881-886.
12.Moody, C. J.; Swann, E. Tetrahedron Lett. 1993, 34, 1987-1988.
13.Tatsuta, K.; Imamura, K.; Itoh, S.; Kasai, S. Tetrahedron Lett. 2004, 45, 2847-2850.
14.Kita, Y.; Tohma, H.; Inagaki, M.; Hatanaka, K.; Yakura, T. J. Am. Chem. Soc. 1992, 114, 2175-2180.
15.Cotterill, A. S.; Moody, C. J.; Roffey, J. R. A. Tetrahedron, 1995, 51, 7223-7230.
16.(a) Naylor, M. A.; Jaffar, M.; Nolan, J.; Stephens, M. A.; Butler, S.; Patel, K. B.; Everett, S. A.; Adams, G. E.; Stratford, I. J. J. Med. Chem. 1997, 40, 2335-2346. (b) Naylor, M. A.; Swann, E.; Everett, S. A.; Jaffar, M.; Nolan, J.; Robertson, N.; Lockyer, S. D.; Patel, K. B.; Dennis, M. F.; Stratford, M. R. L.; Wardman, P.; Adams, G. E.; Moody, C. J.; Stratford, I. J. J. Med. Chem. 1998, 41, 2720-2731. (c) Jaffar, M.; Phillips, R. M.; Williams, K. J.; Mrema, I.; Cole, C.; Wind, N. S.; Ward, T. H.; Stratford, I. J.; Patterson, A. V. Biochem. Pharmacol. 2003, 66, 1199-1206.
17.(a) Cotterill, A. S.; Hartopp, P.; Jones, G. B.; Moody, C. J.; Norton, C. L.; O’Sullivan, N.; Swann, E. Tetrahedron, 1994, 50, 7657-7674. (b) Cotterill, A. S.; Moody, C. J.; Mortimer, R. J.; Norton, C. L.; O’Sullivan, N.; Stephens, M. A.; Stradiotto, N. R.; Swann, E.; Stratford, I. J. J. Med. Chem. 1994, 37, 3834-3843.
18.(a) Wang, C.; Sperry, J. Tetrahedron, 2013, 69, 4563-4577. (b) Khdour, O.; Ouyang, A.; Skibo, E. B. J. Org. Chem. 2006, 71, 5855-5863.
19.(a) Remers, W. A.; Weiss, M. J. J. Am. Chem. Soc. 1966, 88, 804-813. (b) Roth, R. H.; Remers, W. A.; Weiss, M. J. J. Org. Chem. 1966, 31, 1012-1015.
20.Kobayashi, K.; Takeuchi, H.; Seko, S.; Suginome, H. Helv. Chim. Acta. 1991, 74, 1091-1094.
21.Shvartsberg, M. S.; Kolodina, E. A.; Lebedeva, N. I.; Fedenok, L. G. Tetrahedron Lett. 2009, 50, 6769-6771.
22.(a) Knolker, H. J.; Frohner, W. J. Chem. Soc., Perkin Trans. 1, 1998, 173-176. (b) Knolker, H.-J.; Reddy, K. R.; Wagner, A. Tetrahedron Lett. 1998, 39, 8267-8270.
23.Francis A. Carey，« Organic Chemistry »，1992.
24.Catellani, M,: Frignani, F.; Rangoni, A., Angew. Chem. Int. Ed. 1997, 36, 119-122.
25.Wang, X. C.; Gong, W.; Fang, L. Z.; Zhu, R. Y.; Li, S.; Engle, K. M.; Yu. J. Q. Nature, 2015, 519, 334-338.
26.Decharin, N.; Stahl, S. S. J. Am. Chem. Soc. 2011, 133, 5732-5735.
27.Debasish, B.; Sanghamitra, M.; Turrubiartes, L. C.; Banik, B. K. Ultrasonics Sonochemistry, 2012, 19, 969-973.
28.Mehta, G.; Padma, S. Tetrahedron, 1991, 47, 7807-7820.
29.Tseng, C. C.; Wu, Y. L.; Chuang, C. P. Tetrahedron, 2002, 58, 7625-7633.
30.Fujiwara, Y,; Domingo, V.; Seiple, I. B.; Gianatassio, R.; Bel, M. D.; Baran, P. P. S. J. Am. Soc. 2011, 133, 3292-3295.
31.Walker, S. E.; Jordan-Hore, J. A.; Johnson, D. G.; Macgregor, S. A.; Lee, A. L. Angew. Chem. Int. Ed. 2014, 53, 13876-13879.
32.Cameron, D. W.; Scott, P. M.; Todd, L. J. Chem. Soc. 1964, 42-48.
33.Mori Quiroz, L. M.; Clift, M. D., Org. Lett., 2016, 18, 3446-3449.
34. Jiao, L; Bach, T. J. Am. Chem. Soc. 2011, 133, 12990-12993.
35.陳雅倩，碩士論文，中興大學化學研究所，民國104年
36.Luu, Q. H.; Guerra, J. D.; Castaneda, C. M.; Martinez, M. A.; Saunders, J.; Garcia, B. A.; Gonzales, B. V.; Aidunithula, A. R.; Mito, S. Tetrahedron Lett. 2016, 57, 2253-2256.
37.Kobayashi, K.; Shimizu, H.; Srtsaki, A.; Suginome, H. J. Org. Chem. 1991, 56, 3204-3205.
38.Kuo, S. C.; Ibuka, T.; Huang, L. J.; Lien, J. C.; Yean, S. R.; Huang, S. C.; Lednicer, D.; Morris Natschke, S.; Lee, K. H. J. Med. Chem. 1996, 39, 1447-1451.