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研究生: 林綠
Lyu Lin
論文名稱: 便宜而有效合成吲哚類雜環化合物方法之研究
Efficient and Cost-free Protocols for the Synthesis of Heterocyclic Compound with Indole
指導教授: 姚清發
Yao, Ching-Fa
學位類別: 碩士
Master
系所名稱: 化學系
Department of Chemistry
論文出版年: 2014
畢業學年度: 102
語文別: 中文
論文頁數: 145
中文關鍵詞: 吡唑噁二唑咔唑
英文關鍵詞: pyrazole, oxadiazole, carbazole
論文種類: 學術論文
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  • 第一個題目分為兩個部份,第一部份使用碘化亞銅 (copper (I) iodide) 當作催化劑,將二亞苄基丙酮衍生物 (dibenzolideneacetone derivatives) 與苯肼 (phenylhydrazine) 進行環化反應生成吡唑啉(pydrazoline) 衍生物後,再氧化生成吡唑 (pyrazole) 衍生物並以一鍋化反應進行。同時,根據文獻指出,吡唑衍生物具有生物活性,常見於農用化學品和藥物結構中,如殺蟲劑Cyenopyrafen、吡蟎胺、唑蟲酰胺、唑蟎酯和非類固醇消炎止痛藥希樂葆。
    第二部份則是利用二亞苄基丙酮衍生物與苯甲醯肼 (benzoyl hydrazine) 進行反應獲得亞胺 (imine) 衍生物後,在無金屬或酸催化劑的條件下,以微波反應器在短時間內得到1,3,4–噁二唑 (1,3,4–oxadiazole) 衍生物,而1,3,4–噁二唑 (oxadiazole) 衍生物具有生物活性,許多常見藥物都是1,3,4–噁二唑衍生物。
    第二個題目是利用吡唑衍生物與對苯醌 (p–Benzoquinone,BQ) 進行Diels–Alder 反應,在不使用催化劑的條件下,只使用甲苯與醋酸就可得到咔唑 (carbazole) 衍生物。我們在此合成多種取代基的咔唑衍生物。咔唑衍生物具有生物活性,如Clausamines A–G對淋巴瘤細胞具有抗腫瘤的效果。

    The thesis is divided into two chapters. The first chapter is subdivided into two sections. The first section chapter I describes the synthesis of pyrazole derivatives from the dibenzolideneacetone derivatives and phenylhydrazines via copper (I) iodide catalyzed one-pot oxidative C-H amination and aromatization. The pyrazole moiety is present in many important agrochemical and pharmaceutical products, such as the pesticides Cyenopyrafen, Tebufenpyrad, Tolfenpyrad, Fenpyroximate, and nonsteroidalanti-inflammatory drug Celecoxib.
    The second section of Chapter I deals with the synthesis of 1,3,4-oxadiazole derivatives. This method involves the reaction of indole adduct of dibenzolideneacetone derivatives with acylphenylhydrazine in the presence of acetic anhydride under microwave irradiation. This reaction did not need any metal or acidic catalyst. 1,3,4-oxadiazole derivatives possess biological activities and are common drugs structure.
    The chapter II describes the synthesis of carbazole derivatives from the reaction of indole adduct of dibenzolideneacetone phenylhydrazine and benzoquinone in absence of catalyst in toluene and acetic acid. A wide variety of substituted carbazole derivatives were synthesized in this procedure. Carbazole derivatives possess biological activities, such as Clausamines A-G shows activity of antitumor on Raji cell.

    中文摘要 I 英文摘要 II 縮寫對照表 III 壹、便宜且有效合成吡唑與噁二唑化合物方法之研究 1 1.1前言 1 1.1.1吡唑 (pyrazole) 衍生物簡介 1 1.1.2 1,3,4–噁二唑 (oxadiazole) 衍生物的簡介 8 1.1.3微波簡介 12 1.2研究策略與構想 15 1.3結果與討論 16 1.3.1起始物1與苯肼合成吡唑啉 16 1.3.2使用醋酸銅催化脫氫反應 17 1.3.3一鍋化反應以合成具有吡唑的化合物4 19 1.3.4起始物1與苯甲醯肼合成亞胺 28 1.3.5 亞胺衍生物合成1,3,4–噁二唑衍生物 30 1.3.6反應機構的探討 36 1.4結論 40 1.5實驗部份 41 1.5.1 實驗步驟 41 1.5.2 實驗方法 43 1.5.3 光譜資料 45 1.6 參考文獻 69 貳、無催化劑的條件下吲哚衍生物與對苯醌進行Diels–Alder 反應 73 2.1前言 73 2.2研究策略與構想 80 2.3結果與討論 81 2.3.1使用化合物4合成咔唑衍生物 81 2.4.2化合物9的延伸應用 91 2.3.3反應機構的探討 93 2.4結論 95 2.5實驗部份 96 2.5.1 實驗步驟 96 2.5.2 實驗方法 96 2.5.3 光譜資料 98 2.6 參考文獻 109 附錄 111 X–ray單晶繞射 111 1H NMR、13C NMR光譜附圖 145

    part1
    1. (a) Lan, R.; Liu, Q.; Fan, P.; Lin, S.; Fernando, S. R.; McCallion, D.; Pertwee, R.; Makriyannis, A. J. Med. Chem. 1999, 42, 769. (b) Francisco, M. E. Y.; Seltzman, H. H.; Gilliam, A. F.; Mitchell, R. A.; Rider, S. L.; Pertwee, R. G.; Stevenson, L. A.; Thomas, B. F. J. Med. Chem. 2002, 45, 2708. (C) Nakamura-Palacios, E. M.; Moerschbaecher, J. M.; Barker, L. A. CNS Drug Rev. 1999, 5, 43.
    2. (a) Pfizer Inc. WO200621881, 2006. (b) Alton, G.; Bender, S.; Botrous, I.; Christensen, J.; Cui, J. J.; Edwards, M. P.; Funk, L.; Grodsky, N.; Jia, L.; Kania, R. S.; Kung, P.-P.; Li, Q.; McTigue, M.; Meng, J.; Mroczkowski, B.; Nambu, M.; Padrique, E.; Pairish, M.; Ryan, K.; Shen, H.; Timofeevski, S.; Tran-Dube, M.; Yamazaki, S.; Zou, H. J. Med. Chem. 2011, 54, 6342. (C) De Koning, P. D.; McAndrew, D.; Moore, R.; Moses, I. B.; Boyles, D. C.; Kissick, K.; Stanchina, C. L.; Cuthbertson, T.; Kamatani, A.; Rahman, L.; Rodriguez, R.; Urbina, A.; Sandovalnee A. A.; Rose, P. R. Org. Process Res. Dev. 2011, 15, 1018.
    3. (a) Euclises Pharmaceuticals, Inc.; Martinez, E. J.; Talley, J. J.; Jerome, K. D.; Boehm, T. L. WO201412074, 2014. (b) Lill, A.; Stark, H.; Scholich, K.; Stark, H. Tetrahedron Lett. 2013, 54, 6682. (C) Hu, J.; Chen, S.; Sun, Y.; Yang, J.; Rao, Y. Org. Lett. 2012, 14, 5030.
    4. Patil, N. T.; Singh, V. Chem. Commun. 2011, 47, 11116.
    5. Tasch, B. O. A.; Bensch, L.; Antovic , D.; Müller, T. J. J. Org. Biomol. Chem. 2013, 11, 6113.
    6. Gupton, J. T.; Telang, N.; Gazzo, D. F.; Barelli, P. J.; Lescalleet, K. E.; Fagan, J. W.; Mills, B. J.; Finzel, K. L.; Kanters, R. P. F.; Crocker, K. R.; Dudek, S. T.; Lariviere, C. M.; Smith, S. Q.; Keertikar, K. M. Tetrahedron 2013, 69, 5829.
    7. Han, B.; Liu, Z.; Liu, Q.; Yang, L.; Liu, Z.-L.; Yu, W. Tetrahedron 2006, 62, 2492.
    8. Ananthnag, G. S.; Adhikari, A.; Balakrishna, M. S. Catal. Commun. 2014, 43, 240.
    9. Arbačiauskienėa, E.; Vilkauskaitėa, G.; Ellerb, G. A.; Holzerb, W.; Šačkusa, A. Tetrahedron 2009, 65, 7817.
    10. Savarino, A. Expert Opin. Investig. Drugs 2006, 15, 1507.
    11. Sterling Winthrop Inc. US5464848, 1995.
    12. (a) Palazzo,G. et al. J. Med. Chem. 1961, 4, 351. (b) Angeli Francesco DE1097998, 1961.
    13. Tully, W. R.; Gardner, C. R.; Gillespie, R. J.; Westwood, R. J. Med. Chem. 1991, 34, 2060.
    14. Filák, L.; Rokob, T. A.; Vaskó, G. Á.; Egyed, O.; Gömöry, Á.; Riedl, Z.; Hajós, G. J. Org. Chem. 2008, 73, 3900.
    15. Zheng, C.-z.; Wang, L.; Liu, J. J. Mol. Struct. 2012, 1018, 78.
    16. Sadek, M. M. E.; Zagzoug, N. B.; Soccary, N. N. E. Carbohydr. Res. 1993, 250, 323.
    17. Maccioni, E.; Alcaro, S.; Cirilli, R.; Vigo, S.; Cardia, M. C.; Sanna, M. L.; Meleddu, R.; Yanez, M.; Costa, G.; Casu, L.; Matyus, P.; Distinto S. J. Med. Chem. 2011, 54, 6394.
    18. Cristancho, M. Atypical Depression in the 21st Century: Diagnostic and Treatment Issues. Psychiatric Times. 2013.
    19. (a) Gedye, R.; Smith, F.; Westaway, K.; Ali, H.; Baldisera, L.; Laberge, L.; Rousell, R. Tetrahedron Lett. 1986, 27, 279. (b) Giguere, R. J.; Bray, T. L.; Duncan, S. M.; Majetich, G. Tetrahedron Lett. 1986, 27, 4945.
    20. Guirado , A.; Martiz, B.; Andreu, R.; Bautista , D. Tetrahedron 2009, 65, 5958.
    21. Lin, Z.-P.; Li, J.-T. E-Journal of Chemistry 2012, 9, 267.
    22.(a) Patil, N. T.; Singha, V. Chem. Commun. 2011, 47, 11116. (b) Azarifar, D.; Maleki, B. J. Chin. Chem. Soc. 2005, 52, 1215.
    23. (a) Cavaleiro, J. A. S.; Faustino, M. A.F.; Moura, N. M. M.; Neves, M. G. P. M. S.; Silva, A. M. S.; Tome, A. C.; Hannioui, A.; Mojahidi, S.; Rakib, E. M.; Hackbarth, S.; Roeder, B.; Almeida Paz, F. A. Tetrahedron 2012 , 68, 8181. (b) Hoechst-Roussel Pharmaceuticals Inc. US4622326, 1986.
    24. Zhu, X.; Wang, Y.-F.; Ren, W.; Zhang, F.-L.; Chiba, S. Org. Lett. 2013, 15, 3214.
    25. Li, X.; He, L.; Chen, H.; Wu, W.; Jiang, H. J. Org. Chem. 2013, 78, 3636.
    26. Hamada, N. M. M.; Sharshira, E. M. Molecules 2011, 16, 2304.
    part2
    1. (a) Chang, C.-C.; Wu, J.-Y.; Chang, T.-C. J. Chin. Chem. Soc. 2003, 50, 185. (b) Kang, C.-C.; Chang, C.-C.; Chang, T.-C.; Liao, L. J.; Lou, P. J.; Xie, W.; Yeung, E. S. Analyst 2007, 132, 745.
    2. Lebold, T. P.; Kerr, M. A. Org. Lett. 2008, 10, 997.
    3. Tepaske, M. R.; Gloer, J. B.;Wicklow, D. T.; Dowd, P. F. Org. Lett. 1990, 55, 5299.
    4. Mehta, L. K.; Parrick, J.; Payne, F.; Trans, P. J. Chem. Soc. 1993, 1, 1261.
    5. Campeau, L.-C.; Parisien, M.; Jean, A.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 581.
    6. (a) Campeau, L.-C.; Thansandote, P.; Fagnou, K. Org. Lett. 2005, 7, 1857. (b) Smitrovich, J. H.; Davies, I. W. Org. Lett. 2004, 6, 533. (c) Ackermann, L.; Althammer, A. Angew. Chem. Int. Ed. 2007, 46, 1627.
    7. Liégault, B.; Lee, D.; Huestis, M. P.; Stuart, D. R.; and Fagnou, K. J. Org. Chem. 2008, 73, 5022.
    8. Parisien, M.; Valette, D.; Fagnou, K. J. Org. Chem. 2005, 70, 7578.
    9. Noland, W. E.; Konkel, M. J.; Tempesta, M. S.; Cink, R. D.; Powers, D. M.et al. J. Heterocycl. Chem. 1993, 30, 183.
    10. Aboab, B.; Anizon, F.; Conchon, E.; Prudhomme, M. J. Med. Chem. 2007, 50, 4669.
    11. Ding, C.; Tu, S.; Wang, Y.; Zhang, A.; Ding, C.; Li, F.; Yao, Q.; Hu, W.; Tu, S. Adv. Synth. Catal. 2010, 352, 847.
    12. Kong, A.; Han, X.; Lu, X. Org. Lett. 2006, 8, 1339.
    13. Wu, C.-H.; Hung, M.-S.; Song, J.-S.; Yeh, T.-K.; Chou, M.-C.; Chu, C.-M.; Jan, J.-J.; Hsieh, M.-T.; Tseng, S.-L.; Chang, C.-P.; Hsieh, W.-P.; Lin, Y.; Yeh, Y.-N.; Chung, W.-L.; Kuo, C.-W.; Lin, C.-Y.; Shy, H.-S.; Chao, Y.-S.; Shia, K.-S. J. Med. Chem. 2009, 52, 4496.
    14. (a) Abelman, M. M.; Oh, T.; Overman, L. E. J. Org. Chem. 1987, 52, 4133. (b) Nayak, M.; Batra, S. Eur. J. Org. Chem. 2012, 19, 3677 (c) Wu, K.-J.; Dai, L.-X.; You, S.-L. Org. Lett. 2012, 14, 3772.
    15. Vaillard, V. A.; Rossi, R. A.; Martín, S. E. Org. Biomol. Chem. 2011, 9, 4927.
    16. Chen, C.-Y.; Yang, C.-H.; Hu, W.-P.; Vandavasi, J. K.; Chung, M.-I.; Wang, J.-J. RSC Advances 2013, 3, 2710.
    17. Li, Y.; Xu, L.; Liu, T.; Yu, Y.; Liu, H.; Li, Y.; Zhu, D. Org. Lett. 2011, 13, 5692.
    18. (a) Kong, A.; Han, X.; Lu, X. Org. Lett. 2006, 8, 1339. (b) Deb, I.; Yoshikai, N. Org. Lett. 2013, 15 , 4254. (c) Itahara, T.; Kawasaki, K.; Ouseto, F. Bull. Chem. Soc. Jpn. 1984 , 57, 3488.
    19. Conchon, E.; Anizon, F.; Aboab, B.; Prudhomme, M. Synthesis 2008, 16, 2569.

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