臺灣博碩士論文加值系統

本研究設計在兩端對位上有醯胺基團的雙苯醌與3°胺當反應起始物，於鈀金屬催化與優化反應條件下進行一鍋化的反應。經過晶體結構的確認是生成主架構為1,4,5,8-phenanthrenetetraone結構的衍生物7b (當3°胺為NBu3)，結果顯示3°胺在反應過程中不單單當作鹼使用，更重要的是3°胺同時扮演反應物角色，經反應條件優選並分離後7b產率約在40%左右，並經由X-ray單晶繞射所提供之晶體結構推測反應機制為鈀金屬先與3°胺作用後形成亞胺陽離子(imine cation)，之後再經由一連串反應步驟後在醯胺基團處進行環化反應。同時，更獨特的是在雙苯醌原單鍵連接處亦進行環化反應形成苯環結構。
另外，本研究也嘗試在相同實驗條件下進行雙苯醌與1°胺的催化反應，由於目前尚未能得到產物確切晶體結構資料，僅藉由氫光譜、碳光譜與質譜所提供數據來猜測產物主結構為咪唑苯醌類衍生物，但卻發現只有在一端醯胺基團處環化形成咪唑，另一端則走加成反應機制形成amidine，推測其分子結構是由1°胺先扮演親核試劑(nucleophile)攻打醯胺上的羰基後，再經過一連串反應步驟所形成。
針對雙苯醌與2°胺於相同反應條件下進行反應，分離與鑑定結果發現仍然可以得到與3°胺當起始物時相同的產物。

In this work, both diquinone, having two amido groups at opposite positions, and 3° amine as starting materials were used to carry out in an one-pot reaction in presence of palladium salt as catalyst. This catalytic reaction were screened with various reaction conditions to find out the optimized combinations of variable. A new compound 7b was obtained while a 3° amine (NBu3) had been used. The crystal structure of 7b was confirmed by the single crystal X-ray determining process. The structure of 7b reveals that it is having a main framework of 1,4,5,8-phenanthrenetetraone. It indicates that this 3° amine is not used merely as a base during the reaction, and more importantly, it acts as a reactant at the same time. The yield of 7b could be reached about 40% while optimized condition is obtained. The reaction mechanism is therefore proposed and shows that the palladium metal first reacts with the 3° amine to form an imine cation, and then undergoes a cyclization reaction at the amido group after a series of reaction steps. Unexpectedly, a benzene ring is also formed during the formation of 7b presumably through the linking of two quinone rings from 6a. Furthermore, similar reactions were carried out for diquinone with 1° amine. Since the exact crystal structural data of the product has not been obtained yet, the conformation of the product is only proposed by the culminated data available from 1H NMR, 13C NMR and mass spectrometry. The main structure is an imidazole derivative, but it is found that only the amido group at one end cyclizes to form imidazole, and the other side undergoes an addition reaction to form an amidine. It is speculated that the employed amine is firstly acted as nucleophile to attack the carbonyl group on the amide and then the imidazole ring formed latter through a series of sequential reaction steps.
Later, the similar reaction was carried out for diquinone and 2° amine (NHBu2). Interestingly, the same product 7b, as that reaction used 3° amine as the starting material, was obtained after the purification and identification of the observe product.

摘要 i
Abstract ii
目錄 iv
Scheme 目錄 vi
Figure 目錄 ix
Table 目錄 x
本研究化合物編號對照表 xi
第一章 序論 1
第一節 菲類衍生物與1,4,5,8-phenanthrenetetraone 簡介 2
第二節 碳-氫鍵活化與官能基化簡介 14
第三節 苯醌上碳-氫鍵活化與官能基化簡介 18
第四節　研究方向 22
第二章　實驗 23
第一節 光譜儀器介紹 24
第二節 實驗與養晶溶劑處理 27
第三節 實驗藥品 28
第四節 合成與鑑定 31
第三章　結果與討論 47
第一節　具指向基Amido-substituted diquinone與三級胺的催化反應 48
第二節　具指向基Amido-substituted diquinone與一級胺的催化反應 67
第三節 具指向基Amido-substituted diquinone與二級胺的催化反應 72
第四節　未來展望 73
第五章　結論 75
第六章　參考文獻 77
第七章　附錄 82
第一節 光譜數據 83
第二節　晶體數據 118

1.(a) Floyd, A. J.; Dyke, S. F.; Ward, S. E. Chem. Rev. 1976, 76, 509- 562. (b) Wang, Q.; Wang, T.; Ma, H.; Zhang, S.; Li, Z. J.Zhang, M.; Li, F.; Sun, F.; Xiang, J.; Ke, M. Org. Lett. 2018, 20, 3591-3595. (c) Lee, S. H.; McCain, W. C. Wildlife Toxicity.
2."Bardhan Sengupta Synthesis". Comprehensive Organic Name Reactions and Reagents. 49. 2010. pp. 215-219.
3.Ramana, M. M. V.; Potnis, P. V. Synthesis, 1996, 1090-1092.
4.Catellani, M.; Motti, E.; Baratta, S. Org. Lett. 2001, 3, 3611-3614.
5.Cai, X.; Brown, S.; Hodson, P.; Snieckus, V. Can. J. Chem. 2004, 195-205.
6.De Koning, C. B.; Michael, J. P.; Rousseau, A. L. Tetrahedron Lett. 1998, 39, 8725-8728.
7.Tojo, G.; Almeida, J. F.; Castedo, L.; Fernández, D.; Neo, A. G.; Romero, V. Org. Lett. 2003, 5, 4939–4941.
8.Takahashi, T.; Kanno, K. I.; Liu, Y.; Iesato, A.; Nakajima, K. Org. Lett. 2005, 7, 5453–5456.
9.Lautens, M.; Zhao, Y. B.; Mariampillai, B.; Candito, D. A.; Laleu, B.; Li, M. Angew. Chem. Int. Ed. 2009, 48, 1849–1852.
10.Kwong, F. Y.; Fu, W. C.; Wang, Z.; Chan, W. T. K.; Lin, Z. Angew. Chem. Int. Ed. 2017, 56, 7166–7170.
11.Zhong, Y.; Wu, W. Y.; Yu, S. P.; Fan, T. Y.; Yu, H. T.; Li, N. G.; Shi, Z. H.; Tang, Y. P.; Duan, J. A. Beilstein J. Org. Chem. 2019, 15, 291-298.
12.(a) Krohn, K. ; Aslan, A.; Ahmed, I.; Pescitelli, G.; Funaioli, T. Eur. J. Org. Chem. 2009, 5452-5427. (b) Lin, T. H.; Chang, S. J.; Chen, C. C.; Wang, J. P.; Tsao, L. T. J. Nat. Prod. 2001, 64, 1084-1086.
13.Thangaraj, S.; Tsao, W. S.; Luo, Y. W.; Lee, Y. J.; Chang, C. F.; Lin, C. C.; Uang, B. J.; Yu, C. C.; Guh, J. H.; Teng, C. M. Tetrahedron, 2011, 67, 6166-6172.
14.Wang, Y. C. ;Lin, C.H.; Chen, C.M.; Liou, J. P. Tetrahedron Lett. 2005, 46, 8103-8104.
15.Krohn, K.; Loock, U.; Paavilainen, K.; Hausen, B. M.; Schmalle, H. W.; Kiesele, H. ARKIVOC 2001, 1, 88-130.
16.Carreńo, M. C.; Mahugo, J.; Urbano, A. Tetrahedron Lett. 1997, 38, 3047-3050.
17.Kita, Y.; Yasuda, H.; Tamura, Y. Tetrahedron Lett. 1984, 25, 1813-1816.
18.Kraus, G. A.; Melekhov, A. J. Org. Chem. 1999, 64, 1720-1722.
19.Schlűter, A,D.; Blatter, K.; Wegner, G. J. Org. Chem. 1989, 54, 2396-2401.
20.Weber, W. P.; Rosen, B. I. J. Org. Chem. 1977, 42, 3463-3465.
21.Blackburn, E.V.; Timmons, C. J. Chem. Sci. 1969, 482-503.
22.Shi, Y. G.; Mellerup, S. K.; Yuan, K.; Hu, G. F.; Sauriol, F.; Peng, T.; Wang, N.; Chen, P.; Wang, S. Chem. Sci. 2018, 9, 3844-3855.
23.Berdnikova, D. V.; Gulakova, E. N.; Aliyeu, T. M.; Fedorov, Y. V.; Godovikov, I. A.; Fedorova, O. A. J. Org. Chem. 2014, 79, 5533-5537.
24.Ho, T. I.; Wu, J. Y.; Wang, S. L. Angew. Chem. Int. Ed. 1999, 38, 2558-2560.
25.Zhang, Z.; Han, J.; Liang, Y.; Li, Y.; Li, C.; Wang, R.; Feng, S. Org. Lett. 2017, 19, 3552-3555.
26.Kraus, G. A.; Hoover, K.; Zhang, N. Tetrahedron Lett. 2002, 43, 5319-5321.
27.Wu, Y. K.; Wang, S. M.; Cui, J. R.; Jian, Y. J. Chin. J. Chem., 2006, 24, 1163-1169.
28.William H. Brown，Organic Chemistry, second edition..
29.Lautens, M.; Ye, J. Nature Chemistry, 2015, 863-870.
30.Yu, J. Q.; Laforteza, B. N.; Chan, Kelvin. S. L. Angew. Chem. Int. Ed. 2015, 54, 11143-11146.
31.(a) Catellani, M.; Ca，, N. D.; Fontana, M.; Motti, E. Acc. Chem. Res. 2016, 49, 1389-1400. (b) Catellani, M.; Frignani, F.; Rangoni, A. Angew. Chem. Int. Ed. Engl. 1997, 36, 119-122.
(c) Catellani, M.; Cugini, F. Tetrahedron 1999, 55, 6595-6602.
32.Dong, G.; Dong, Z.; Wang, J. J. Am. Chem. Soc. 2015, 137, 5887-5890.
33.Yu, J. Q.; Shen, P. X.; Wang, X. C.; Wang, P.; Zhu, R. Y. J. Am. Chem. Soc. 2015, 137, 11574-11577.
34.(a) Baran, P. H.; Fujiwwara, Y.; Domingo, V.; Seiple, I. B.; Gianatassio, R.; Bel, M. D. J. Am. Chem. Soc. 2011, 133, 3292-3295. (b) Yuan, P.-T.; Pai, C.-H.; Huang, S.-Z.; Hong, F.-E. Tetrahedron 2017, 73, 6786-6794. (c) Chang Y-C, Yuan P-T, Hong F-E. Eur J Org Chem. 2017, 2441-2450.
35.König, B.; Schroll, P.; Hari, D. P. ChemistryOpen. 2012, 1, 130-133.
36.Felpin, F. X.; Honraedt, A.; Callonnec, F. L.; Grognec, E. L.; Fernandez, V. J. Org. Chem. 2013, 78, 4604-4609.
37.(a) Lee, A. L.; Macgregor, S. A.; Walker, S. E.; Jordan-Hore, J. A.; Johnson, D. G. Angew. Chem. Int. Ed. 2014, 53, 13876-13879. (b) Ge, B.; Wang, D.; Dong, W.; Ma, P.; Li, Y.; Ding, Y. Tetrahedron Lett. 2014, 55, 5443. (c) Molina, M. T.; Navarro, C.; Moreno, A.; Csaky, A. G. Org. Lett. 2009, 11, 4938-4941. (d) Ortega, A.; Rincón Á; Jiménez-Aliaga, K. L.; Bermejo-Bescós, P.; Martín-Aragón, S.; Molina, M. T.; Csákÿ, A. G. Bioorg. Med. Chem. Lett. 2011. 21. 2183-2187. (e) Echavarren, A. M.; de Frutos, O.; Tamayo,N.; Noheda, P.; Calle, P. J. Org. Chem. 1997, 62, 4524-4527. (f) Itahara, T. J. Org. Chem. 1985, 50, 5546-5550.
38.(a) Yu, X. Q.; Zhang, J.; Wang, G.; Wang, S.; Wang, J. Chem. Commun., 2012, 48, 11769-11771. (b) Maiti, D.; Deb, A.; Manna, S.; Maji, A.; Dutta, U. Eur. J. Org. Chem. 2013, 5251-5256. (c) Komeyama, K.; Kashihara, T.; Takaki, K. Tetrahedron Lett. 2013, 54, 1084-1086. (d) Singh, P. P.; Aithagani, S. K.; Yadav, M.; Singh, V. P.; Vishwakarma, R. A. J. Org. Chem. 2013, 78, 2639-2648.
39.Ding, Y.; Wang, D.; Ge, B.; Li, L.; Shan, J. J. Org. Chem. 2014, 79, 8607-8613.
40.Akamanchi, K. G.; Patil, P.; Nimonkar, A. J. Org. Chem. 2014, 79, 2331-2336.
41.Wang, D.; Yu, X.; Ge, B.; Miao, H.; Ding, Y. Chin. J. Org. Chem. 2015, 35, 676-680. (b) Jardim, G.; Lima, D.; Valença, W.; Cavalcanti, B.; Pessoa, C.; Rafique, J.; Braga, A.; Jacob, C.; da Silva Júnior, E.; da Cruz, E. J. M. Molecules. 2018, 23, 83. (c) Jardim, G. A.; Bower, J. F.; da Silva Júnior, E. N. Org. Lett. 2016, 18, 4454-4457. (d) Demchuk, O. G.; Michal Pietrusiewicz, K. Synlett 2009, 7, 1149-1153.
42.(a) Chen, X-L.; Zeng, F-L.; He, S-Q.; Sun, K.; Liu, Y.; Fu, R.; Qu, L-B.; Zhao, Y-F.; Yu, B. Org. Chem. Front. 2019, 6, 1476-1480.
(b) Lisboa, C. D. S.; Santos, V. G.; Vaz, B. G.; de Lucas, N. C.; Eberlin, M. N.; Garden, S. J. J. Org. Chem. 2011, 76, 5264-5273. (c) Sun J-W, Wang X-S, Liu Y. J Org Chem. 2013, 78, 10560-10566. (d) Inman, M.; Moody, C. J. J. Org. Chem. 2010, 75, 6023-6026.
43.(a) Chen, S. W.; Hong, F. -E, Chemistryselect, 2017, 2, 10232-10238.
44.周家男，碩士論文，中興大學化學研究所，民國107年
45.Tseng, T.-H.; Lin, W.-L.; Chen, Z.-H.; Lee, Y.-J.; Shie, M.-S.; Lee, K.-F.; Shen, C.-H.; Kuo, H.-C. Transl Med. 2016, 14, 263.
46.Hsu, J.-L.; Lee, Y.-J.; Leu, W.-J.; Dong, Y.-S.; Pan, S.-L.; Uang, B.-J.; Guh, J.-H. The Journal of urology. 2014, 191, 1429-1438.