簡易檢索 / 詳目顯示

研究生: 方家齊
Fang, Chia-Chi
論文名稱: 壹、三氯化鋁催化分子內SN1反應與氯化生成四氫吡啶[2,1-a]異吲哚酮衍生物 貳、微波輔助銅(I)催化三成份串級反應合成氰基吡啶衍生物
I. Aluminum Trichloride Catalyzed Chlorinative Intramolecular SN1 Reaction for the Synthesis of Tetrahydropyrido [2,1-a] isoindolones (Valmerins) Derivatives II. Microwave Assisted Synthesis of Cyanopyridine Derivative via Copper(I) Catalyzed Three-Component Cascade Reaction
指導教授: 姚清發
Yao, Ching-Fa
口試委員: 柳如宗
Liu, Ju-Tsung
林文偉
Lin, Wenwei
姚清發
Yao, Ching-Fa
口試日期: 2022/06/27
學位類別: 碩士
Master
系所名稱: 化學系
Department of Chemistry
論文出版年: 2022
畢業學年度: 110
語文別: 中文
論文頁數: 125
中文關鍵詞: SN1反應三氯化鋁四氫吡啶[2,1-a]異吲哚酮微波輔助反應3-氰基吡啶
英文關鍵詞: SN1 Reaction, Aluminum Trichloride, Valmerins, Microwave Assisted Reaction, 3-Cyanopyridine
DOI URL: http://doi.org/10.6345/NTNU202200722
論文種類: 學術論文
相關次數: 點閱:104下載:6
分享至:
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
  • 本篇論文分為兩個獨立章節,每個章節各自包含前言、研究目標、實驗結果與討論以及結論。
    第一章節為〈三氯化鋁催化分子內SN1反應與氯化生成四氫吡啶[2,1-a]異吲哚酮衍生物〉主要探討了四氫吡啶[2,1-a]異吲哚酮及其衍生物在化學合成上的發展和應用,實驗結果與討論則是將3-羥基-3-呋喃基-N-丁烯基異吲哚啉在酸性催化下生成一穩定的碳陽離子,經由SN1的反應途徑成功合成了四氫吡啶[2,1-a]異吲哚酮衍生物。
    第二章節為〈微波輔助銅(I)催化三成份串級反應合成氰基吡啶衍生物〉主要介紹了3-氰基吡啶在醫學上的應用以及其合成方法,實驗結果部分則是成功利用微波反應器將3-溴-3-苯基丙烯、3-酮基-3-苯基丙腈和醋酸銨在碘化亞銅的催化下形成產物2,6-二苯基-3-氰基吡啶,同時也對不同官能基受質進行反應產率的測試,都可以得到不錯的結果,可以應用在未來的合成策略當中。

    The content of the thesis is divided into two chapters, each chapter respectively includes preface, research goal, results and discussion, and conclusion.
    Chapter I is‘Aluminum Trichloride Catalyzed Chlorinative Intramolecular SN1 Reaction for the Synthesis of Tetrahydropyrido [2,1-a] isoindolones (Valmerins) Derivatives’. We introduce the biological activity and the usage of Valmerins in medicine development. The review on the synthesis of Valmerins derivatives was also included in this chapter. This chapter concludes with the goals and motivation of research topic which is about the SN1 reaction of 3-hydroxy-3-furyl-N-alkenylisoindoline derivatives. The starting materials were synthesized from N-butenyl-2-iodobenzamide derivatives and propargyldiketone compounds in the presence of the copper catalyst, which generated a very stable carbocation after elimination of hydroxyl group. This carbocation intermediate can undergo the SN1 reaction effectively.
    Chapter II is‘Microwave Assisted Synthesis of Cyanopyridine Derivative via Copper(I) Catalyzed Three-Component Cascade Reaction’. We summarize the synthetic applications, the medicinal properties, and the synthetic method of the cyanopyridine derivatives. The research topic also describes the synthesis of 2,6-aryl-3cyanopyridine derivatives. 3-Bromocinnamaldehyde, 3-oxo-3phenylpropanenitrile and ammonium acetate, undergo a three-component one-pot reaction in the presence of copper catalyst under microwave. The expected products are obtained in high yields, and all of the reactions are clean.

    中文摘要 i Abstract ii 第壹章、三氯化鋁催化分子內SN1反應與氯化生成四氫吡啶[2,1-a]異吲哚酮衍生物 1-1、前言 3 1-1-1、1-異吲哚啉酮(1- Isoindolinone)的介紹 3 1-1-2、具有生物活性的吲哚啉西啶( Indolizidine)生物鹼 4 1-1-3、1-異吲哚啉酮衍生物的合成 5 1-1-4、四氫吡啶[2,1-a]異吲哚酮( Tetrahydropyrido [2,1-a]isoindolones, Valmerins)的合成 7 1-1-5、微波反應在有機合成的應用 11 1-2、實驗目標 14 1-3、實驗結果與討論 16 1-3-1、起始物的製備 16 1-3-2、合成四氫吡啶[2,1-a]異吲哚酮衍生物 18 1-3-2-1、最佳化條件選擇 18 1-3-2-2、以N-丁炔基-1-異吲哚啉酮為起始物 20 1-3-2-3、反應機構的探討 22 1-3-2-4、不同取代基受質測試 23 1-4、結論 25 1-5、實驗方法 26 1-5-1、分析儀器及基本實驗操作 26 1-5-2、實驗步驟 28 1-6、參考文獻 33 1-7、光譜資料 35 第貳章、微波輔助銅(I)催化三成份串級反應合成氰基吡啶衍生物 2-1、前言 80 2-1-1、菸鹼酸( niacin)的介紹 80 2-1-2、菸鹼酸的生物活性及藥物介紹 81 2-1-3、3-氰基吡啶( 3-cyanopyridine)的介紹與合成 83 2-1-4、微波反應在有機合成的應用 85 2-2、實驗目標 87 2-3、實驗結果與討論 88 2-3-1、起始物製備 88 2-3-2、合成3-氰基吡啶的最佳化條件選擇 89 2-3-3、反應機構的探討 91 2-3-4、不同取代基受質測試 93 2-4、結論 95 2-5、實驗方法 96 2-5-1、分析儀器及基本實驗操作 96 2-5-2、實驗步驟 98 2-6、參考文獻 100 2-7、光譜資料 102

    1-6、參考文獻
    1. Verma, A.; Patel, S.; Kumar, A.; Yadav, A.; Kumar, S.; Jana, S.; Sharma, S.; Prasad, C.D.; Kumar, S. Chemical Communications 2015, 51 (7), 1371-1374.
    2. Palumbo, A.; Hajek, R.; Delforge, M.; Kropff, M.; Petrucci, M. T.; Catalano, J.;Gisslinger, H.; Wiktor-Jędrzejczak, W.; Zodelava, M.; Weisel, K. New England Journal of Medicine 2012, 366 (19), 1759-1769.
    3. Carter, B. L.; Ernst, M. E.; Cohen, J. D. Hypertension 2004, 43 (1), 4-9.
    4. Lunn, M. R.; Root, D. E.; Martino, A. M.; Flaherty, S. P.; Kelley, B. P.; Coovert, D. D.; Burghes, A. H.; thi Man, N.; Morris, G. E.; Zhou, J.; et al.Chemistry & Biology 2004, 11 (11), 1489-1493.
    5. Kanamitsu, N.; Osaki, T.; Itsuji, Y.; Yoshimura, M.; Tsujimoto, H.; Soga, M. Chemical and Pharmaceutical Bulletin 2007, 55 (12), 1682-1688.
    6. Hussein, Z.; Mulford, D. J.; Bopp, B. A.; Granneman, G. R. Br J Clin Pharmacol 1993, 36 (4), 357-361.
    7. (a) Davidson, B. S. Chemical Reviews 1993, 93 (5), 1771-1791. (b)Faulkner, D. J. Natural Product Reports 1994, 11 (0), 355-394. (c) Faulkner, D. J. Natural Product Reports 1995, 12 (3), 223-26. (d) Faulkner, D. J. Natural Product Reports 1996, 13 (2), 75-125. (e) John Faulkner, D. Natural Product Reports 1999, 16 (2), 155-198.
    8. Cook, D.; Gardner, D. R.; Pfister, J. A. Journal of Agricultural and Food Chemistry 2014, 62 (30), 7326-7334.
    9. Dorling, P. R.; Huxtable, C. R.; Colegate, S. M. Biochem J 1980, 191(2), 649-651.
    10. Cutter, A. C.; Miller, I. R.; Keily, J. F.; Bellingham, R. K.; Light, M. E.; Brown, R. C. D.
    Organic Letters 2011, 13 (15), 3988-3991.
    11. Li, X.; Wang, X.; Tian, Z.; Zhao, H.; Liang, D.; Li, W.; Qiu, Y.; Lu, S. J Mol Model 2014, 20 (9), 2407.
    12. Augner, D.; Gerbino, D. C.; Slavov, N.; Neudörfl, J.-M.; Schmalz, H.-G. Organic Letters 2011, 13 (19), 5374-5377.
    13. Nozawa-Kumada, K.; Kadokawa, J.; Kameyama, T.; Kondo, Y. Organic Letters 2015, 17 (18), 4479-4481.
    14. 謝孟諠. 國立臺灣師範大學化學系碩士論文 2016.
    15. Wada, M.; Nakai, H.; Sato, Y.; Hatanaka, Y.; Kanaoka, Y. Tetrahedron 1983, 39 (16), 2691-2698.
    16. Alsarabi, A. E.; Canet, J.-L.; Troin, Y. Tetrahedron Letters 2004, 45(49), 9003-9006.
    17. Maity, A. K.; Roy, S. The Journal of Organic Chemistry 2012, 77 (6), 2935-2941.
    18. Boulahjar, R.; Ouach, A.; Matteo, C.; Bourg, S.; Ravache, M.; Guével, R. l.; Marionneau, S.; Oullier, T.; Lozach, O.; Meijer, L.; et al. Journal of Medicinal Chemistry 2012, 55 (22), 9589-9606.
    19. Oukoloff, K.; Buron, F.; Routier, S.; Jean, L.; Renard, P. Y. European Journal of
    Organic Chemistry 2015, 2015 (11), 2450-2456.
    20. Giguere, R. J.; Bray, T. L.; Duncan, S. M.; Majetich, G. Tetrahedron Letters 1986, 27 (41), 4945-4948.
    21. 陳雨農.國立臺灣師範大學化學系碩士論文 2021.

    2-6、參考文獻
    1. Henderson, L.M., Annual Review of Nutrition 1983, 3 (1), 289-307
    2. Hegyi, J.; Schwartz, R. A.; Hegyi, V., International Journal ofDermoatology 2004, 43 (1), 1-5
    3. Hakozaki, T.; Minwalla, L.; Zhuang, J.; Chhoa, M.; Matsubara, A.;Miyamoto, K.; Greatens, A.; Hillebrand, G. G.; Bissett, D.L.; Boissy, R. E., British Journal of Dermatology 2002, 147 (1), 20-31
    4. (a) VK Lule, S Garg, SC Gosewade, and SK Tomar, Encyclopedia of Food and Healthy p63-72. (b) Jacques Genest and Peter Libby,
    Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine,
    48, 960-982
    5. 林昆吾. 國立臺灣師範大學化學系碩士論文. 2021.
    6. Foster, J. W.; Moat, A. G., Microbiological Reviews 1980, 44 (1),83-105.
    7. Wan, P.; Moat, S.; Anstey, A., British Journal of Dermatology2011, 164 (6), 1188-1200.
    8. El-Enein, A.; Ahmed, M.; Hafez, Y. S.; Salem, H.; Abdel, M.,Nutrition reports international 1983.
    9. Fuccella, L. M.; Goldaniga, G.; Lovisolo, P.; Maggi, E.; Musatti,L.; Mandelli, V.; Sirtori, C. R., Clinical Pharmacology & Therapeutics1980, 28 (6), 790-795.
    10. S. M. McElvain Madison, Wisconsin. A. Goese, Journal of the American Chemical Society 1941, 63, 2283.
    11. Meth-Cohn, Otto; Wang, Mei-Xiang, Tetrahedron Letters 1995,36(52), 9561-9564.
    12. Petrich, S. A.; Hicks, F. A.: Wilkinson, D.R.; Tarrant, J. G.; Bruno, S. M.; Vargas, M.; Hosein, K. N.; Gupton, J. T.; Sikorski, J. A., Tetrahedron 1995, 51 (6), 1575-1584.
    13. Donohoe, T. J.; Basutto, J. A.; Bower, J. F.; Rathi, A., Organic Letters 2011, 13 (5), 1036-1039.
    14. Giguere, R. J.; Bray, T. L.; Duncan, S. M.; Majetich, G. Tetrahedron Letters 1986, 27 (41), 4945-4948.
    15. 余保興, 國立臺灣師範大學化學系碩士論文. 2020.
    16. Kim, B. R.; Lee, H.-G.; Kang, S.-B.; Jung, K.-J.; Sing, G. H.; Kim,
    J.-J.; Lee, S.-G.; Yoon, Y.-J., Tetrahedron 2013, 69 (48), 10331-10336.

    下載圖示
    QR CODE