研究生: |
王振羽 Wang, Chen-Yu |
---|---|
論文名稱: |
利用苯乙腈作為苯甲醯化試劑來合成3-羥基異吲哚啉-1-酮衍生物 Synthesis of 3-Hydroxyisoindolin-1-one Derivatives by Exploiting the Role of Benzylcyanide as a Benzoyl Synthons |
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: | 2019 |
畢業學年度: | 107 |
語文別: | 中文 |
論文頁數: | 106 |
中文關鍵詞: | 3-羥基異吲哚啉-1-酮 、氯化亞銅 、2-碘苯甲醯胺 、苯乙腈 |
英文關鍵詞: | 3-hydroxyisoindolin-1-one, Copper(I) chloride, 2-iodobenzamide, benzyl cyanide |
DOI URL: | http://doi.org/10.6345/NTNU201900443 |
論文種類: | 學術論文 |
相關次數: | 點閱:114 下載:22 |
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 |
論文主要分為二個章節。 第壹章介紹3-羥基異吲哚啉酮類化合物與合成的方法以及這些化合物作為藥物的應用,同時敘述本研究的動機和目標。
第貳章是利用銅來催化反應以合成3-羥基異吲哚啉-1-酮衍生物。本研究中,我們開發了一種有效的合成方法,在使用氯化亞銅試劑的條件下,2-碘苯甲醯胺可以和苯乙腈化合物反應而合成出具有生物活性的3-羥基異吲哚啉-1-酮。在此研究,苯乙腈首次被報導可以成功地用來當作苯甲醯化試劑來合成3-羥基異吲哚啉-1-酮。有趣的是,形成3-羥基異吲哚啉-1-酮的反應路徑中,同時涉及了一種新反應的途徑,包括碳的降解,並接著環的收縮。此反應在經由一鍋化反應的方式中產生了良好至中等產率的產物。同時我們也成功的利用此反應來合成出許多具不同取代基的3-羥基異吲哚啉-1-酮衍生物。
The thesis is mainly divided into two chapters. The first chapter is the preface of the thesis, which gives a simple introduction of 3-hydroxyisolindolinone compounds, brief literature survey on synthetic methods and utilization of these compounds as pharmaceutical. Then we disclose our research motive and research goals at the end of the first chapter.
Chapter II dealt with the Copper catalyzed synthesis of 3-hydroxyisoindolin-1-one derivatives by exploiting the use of benzylcyanide as benzoyl synthon. Here, we developed an efficient protocol for the synthesis of biologically active 3-hydroxyisoindolin-1-one from 2-iodobenzamides and benzyl cyanide in the presence of CuCl catalyst. For the first time, benzyl cyanide has successfully exploited as benzoyl synthon for the synthesis of 3-hydroxyisoindolin-1-ones. Interestingly, the mechanism for the formation of 3-hydroxyisoindolin-1-ones involves a novel pathway which involves carbon degradation followed by ring contraction. Good to moderate yields of products were obtained in one-pot. A wide range of substrates tested for this reaction.
(1) Musa, H. A. Z.; Salim, S. S.; Sabri, F.; Maurice, S.; Phytochemistry 1987, 26, 1233-1234
(2) (a) Fajardo, V.; Elango, V.; Cassels, B. K.; Shamma, M. Tetrahedron Lett. 1982, 23, 39. (b) Fang, F. G.; Danishefsky, S. J. Tetrahedron Lett. 1989, 30, 2747.
(3) (a) Hardcastle, I. R.; Ahmed, S. U.; Atkins, H.; Farnie, G.; Golding, B. T.; Griffin, R. J.; Guyenne, S.; Hutton, C.; Källblad, P.; Kemp, S. J.; Kitching, M. S.; Newell, D. R.; Norbedo, S.; Northen, J.; Reid, R. J.; Saravanan, K.; Willems, H. M.; Lunec, J. J. Med. Chem. 2006, 49, 6209. (b) Hardcastle, I. R.; Liu, J.; Valeur, E.; Watson, A.; Ahmed, S. U.; Blackburn, T. J.; Bennaceur, K.; Clegg, W.; Drummond, C.; Endicott, J. A.; Golding, B. T.; Griffin, R. J.; Gruber, J.; Haggerty, K.; Harrington, R. W.; Hutton, C.; Kemp, S.; Lu, X.; McDonnell, J. M.; Newell, D. R.; Noble, M. E.; Payne, S. L.; Revill, C. H.; Riedinger, C.; Xu, Q.; Lunec, J. J. Med. Chem. 2011, 54, 1233. (c) Dempster, R. K.; Luzzio, F. A. Tetrahedron Lett. 2011, 52, 4992.
(4) Suyavaran, A.; Ramamurthy, C.; Mareeswaran, R.; Shanthi, Y. V.; Selvakumar, J.; Mangalaraj, S.; Kumar, M. S.; Ramanathan, C. R.; Thirunavukkarasu, C. Bioorg. Med. Chem. 2015, 23, 488.
(5) (a) Jan, E.; Andrzej, J.; Krzysztof, C.; Aleksandra, K. S.; Monatshefte für Chemie. 1990, 121, 909. (b) Bousquet, T.; Fleury, J.-F.; Daïch, A.; Netchaitaïlo, P. Tetrahedron 2006, 62, 706. (c) Zhou, Y.; Zhai, Y.; Li, J.; Ye, D.; Jiang, H.; Liu, H. Green Chem. 2010, 12, 1397. (d) Griesbeck, A. G.; Nazarov, N.; Neudörfl, J. M.; Heffen, M. Green Chem. 2012, 14, 3004. (e) Sharma, S.; Park, E.; Park, J.; Kim, I. S. Org. Lett. 2012, 14, 906. (f) Qingzhen, Y.; Nana, Z.; Jianhui, H.; Shaonan, L.; Yi, Z.; Xiaoxiao, Y.; Kang, Z.; Chem. Eur. J. 2013, 19, 11184. (g) DeGlopper, K. S.; Dennis, J. M.; Johnson, J. B. Tetrahedron Lett. 2014, 55, 1843. (h) Fei, L.; Zexiang, L.; Chenguang, Z.; Xiang, L.; Cheng, M.; J. Am. Chem. Soc. 2014, 136, 10914. (i) Jacqueline, J.; Byeong-Seon, K.; Patrick, J. W.; Adv. Synth. Catal. 2016, 358, 2829. (j) Jinhai, S.; Qihua, Y.; Qi, F.; Changsheng, K.; Huabin, H.; Li, Z.; Zhixia, Z.; Org. Lett. 2017, 19, 5170. (k) Dong-Mei, Y.; Quan-Qing, Z.; Li, R.; Jia-Rong, C.; Wen-Jing, X.; Chem. Eur. J. 2018, 24, 16895 – 16901.
(6) 王振權,苯乙腈的區域選擇開關反應,國立臺灣師範大學化學系碩士論文,民103[2014]