簡易檢索 / 詳目顯示

回結果列表
研究生： 林嘉祺
論文名稱： 利用Tiemann 重排反應製備腈胺及不對稱尿素
Facile Synthesis of Cyanamides and Unsymmetrical Ureas via Tiemann Rearrangement
指導教授： 簡敦誠
學位類別： 碩士
Master
系所名稱： 化學系
Department of Chemistry
論文出版年： 2012
畢業學年度： 100
語文別： 中文
論文頁數： 94
中文關鍵詞： 腈胺
英文關鍵詞： cyanamide
論文種類： 學術論文
相關次數： 點閱：59  下載：1 
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

    • 本論文的第一部份探討由 pyrrole 合成具有 [5,7] 雙環的 pyrrolo[2,3-c]azepin-8-one。有一系列海洋天然物的結構已被證實含有 pyrrole 和 imidazole 單元，例如 hymenin。海洋生物鹼 hymenin的主要結構是 pyrrole 組成的 [5,7] 環結構。我們嘗試以 N,N-dimethyl 3-[N-benzyl-N-(1-methylpyrrole-2-carbonyl)amino]propionamide (35) 與三氯氧磷進行 Vilsmeier-Haack 反應合成 hymenin 的 [5,7] 環結構，pyrrolo[2,3-c]azepin-8-one。
    　　第二部分是我們意外地發現一個條件溫和且有效率的新方法去合成苯氰胺。利用苯環上有各種取代基的 benzonitrile 製備 carboxamidoxime，再利用 Tiemann 重排反應可以得到對應的苯氰胺產物，此重排反應與苯環上的電子效應有很大的關連性，經由一系列的實驗得知缺電子的苯環不利於反應，此方法的優點是不用使用金屬或有毒的氰化物，也可以有效率地合成苯氰胺，之後我們利用苯氰胺合成 benzoxazole 或 benzimidazole 等雜環。同時，在酸性條件下可以也可以有效地將苯氰胺水解成尿素，或者加入 anthranilate 反應形成 quinazolinone。另外，當 carboxamidoxime 的胺基上有取代基時，用同樣的方法可以得到不對稱的尿素，多樣性的反應可以提供廣大的合成應用。

    　　The first part of the thesis is to investigate the synthesis of pyrrolo [2,3-c]azepin-8-one from pyrrole. A series of marine natural products have been identified to contain pyrrole and imidazole units such as hymenin. The structure of hymenin consists of bicyclic pyrrolo[2,3-c] azepin-8-one ring. N,N-Dimethyl 3-[N-benzyl-N-(1-methylpyrrole-2- carbonyl)amino] propionamide was treated with phosphorus oxychloride to undergo Vilsmeier-Haack reaction to afford the bicyclic pyrrolo[2,3-c]azepin-8-one.
    　　In the second part of the thesis, we discovered a novel and efficient synthesis for phenylcyanamides under a mild condition. Various aryl cyanamides were obtained from the aryl carboxamide oxime, prepared from the corresponding aryl nitriles, via the Tiemann rearrangement. The rearrangement is highly associated with the electronic property on the arene ring. The advantage of this methodology is to avoid the use of metals or toxic cyanides and it provides an efficient synthesis for a variety of aryl cyanamides. We also demonstrated that the phenyl cyanamides can be used for the synthesis of benzoxazoles or benzimidazoles. In addition, under the acid conditoin, the phenyl cyanamides could undergo hydrolysis to give corresponding the phenyl ureas. Furthermore, it reacted with anthranilates to afford quinazolinones. We can also use the above method to prepare unsymmetrical ureas from the carboxamide oximes which have substituents on the amino groups. The reaction will provide a diverse application in organic synthesis.

    藥品試劑縮寫對照表……………………………………………………1 第一章 設計合成 Hymenin 類似物…………………………………2 　　1.1 緒論…………………………………………………………… 2 　　1.2 結果與討論……………………………………………………4 　　1.3 結論　………………………………………………………12 第二章 緒論……………………………………………………………13 第三章 文獻回顧與合成應用…………………………………………16 第四章 結果與討論……………………………………………………………22 第五章 結論………………………………………………………………………41 第六章 儀器設備與實驗步驟………………………………………………42 6.1 一般實驗處理…………………………………………………………42 6.2 實驗儀器………………………………………………………………43 6.3 實驗步驟………………………………………………………………44 第七章 參考文獻………………………………………………………………90 附錄………………………………………………………………………………94

    1. Al Mourabit, A.; Potier, P. Eur. J. Org. Chem. 2001, 237-243.
    2. Hoffmann, H.; Lindel, T. Synthesis 2003 , 1753-1783.
    3. Bickmeyer, U.; Grube, A; Klings, K.-W.; Koeck, M. Toxicon 2007, 50, 490-497.
    4.Zoellinger, M.; Kelter, G.; Fiebig, H.-H.; Lindel, T. Bioorg. Med. Chem. Lett. 2007, 17, 346-349.
    5.Xu, Y.Z.; Yakushijin, K.; Horne, D.A. J. Org. Chem. 1997, 62, 456-464
    6.Chang, C. C. Synthesis of the Tricyclic A-B-C Ring of Marine Alkaloid Isophakellin via the Electrophilic Aromatic Substitution Reactions; M. Sc. Thesis, National Taiwan Normal University, 2010
    7. Palmer, M. H.; Leitch, D. S.; Greenhalgh, C.W. Tetrahedron 1978. 34, 1015-1021
    8.Cloez, S. and Cannizzaro, S. C.R. Acad. Sci. 1851, 32, p 62
    9. Kurzer, F.; Sanderson, Phyllis. M., J. Chem. Educ. 1956, 33, 452-459
    10. Nekrasov, D. D. Russ. J. Org. Chem. 2004, 40, 1387-1402.
    11. Shikhaliev, Kh. S.; Shestakov, A. S.; Medvedeva, S. M.; Gusakova, N.V. Russ. Chem. Bull., Int. Ed. 2008, 57, 170-176.
    12. Zhou, J.; Fang. J. J. Org. Chem. 2011, 76, 7730-7736.
    13. Kumar, R.; Rai, D.; Sharma, S. K.; Saffran, H. A.; Blush, R.; Tyrrell, D. L. J. J. Med. Chem. 2001, 44, 3531–3538.
    14. Lu, Y.; Li, C.-M.; Wang, Z.; Chen, J.; Mohler, M. L.; Li, W.; Dalton, J. T.; Miller, D. D. J. Med. Chem. 2011, 4678-4693.
    15. Imtiaz, A.; Bose, S. K.; Pavese, N.; Ramlackhansingh, A.; Turkheimer, F.; Hotton, G.; Hammers, A.; Brooks, D. J. Brain. 2011, 134, 979-986.
    16. Shirota, F. N.; Stevens-Johnk, J. M.; DeMaster, E. G.; Nagasawa
    H. T. J. Med. Chem. 1997, 40, 1870-1875.
    17. Crutchley, R. J.; Naklicki, M. L. Inorg. Chem. 1989, 28, 1955-1958.
    18. Naklicki, M. L.; Crutchley, R. J. Inorg. Chem. 1989, 28, 4226-4229.
    19. Kabešová, M.; Boca, R.; Melníck, M.; Valigura, D.; Dunaj-Jurco, M. Coord. Chem. Rev. 1995, 140, 115-135.
    20. Aquino, M. A. S.; Lee, F. L.; Gabe, E. J.; Bensimon, C.; Greedan, J. E.; Crutchley, R. J. J. Am. Chem. Soc. 1992, 114, 5130-5140.
    21. Crutchley, R. J. Coord. Chem. Rev. 2001, 219-221, 125-155.
    22. Nomura, R.; Hasegawa, Y.; Ishimoto, M.; Toyosaki, T.; Matsuda, H.
    J. Org. Chem. 1992, 57, 7339-7342.
    23. Gabriele, B.; Salerno, G.; Mancuso, R.; Costa, M. J. Org. Chem. 2004, 69, 4741-4750.
    24. Tao, Z. F.; Wang, L.; Stewart, K. D.; Chen, Z.; Gu, W.; Bui, H. M.; Merta, P.; Zhang, H.; Kovar, P.; Johnson, E.; Park, C.; Judge, R.; Rosenberg, S.; Sowin, T.; Lin, N. H. J. Med. Chem. 2007, 50, 1514-1527.
    25. Shia, K. S.; Li, W. T.; Chang, C. M.; Hsu, M. C.; Chern, J. H.; Leong, M. k.; Tseng, S. N.; Lee, C. C.; Lee, Y. C.; Chen, S.J.; Peng, K. C.; Tseng, H. Y.; Chang, Y. L.; Tai, C. L.; Shih, S. R. J. Med. Chem. 2002, 45, 1644-1655.
    26. Fortin, S.; Wei, L.; Moreau, E.; Lacroix, J.; Cote, M. F.; Petitclerc, E.; Kotra, L. P.; Gaudreault, R. C. J. Med. Chem. 2011, 54, 4559–4580.
    27. Wang, L.; Liu, S.; Li, Z.; Yu, Y. Org. Lett. 2011, 13, 6137-6139.
    28. Partridge, M. W.; Turner, H. A. J. Pharm. Pharmacl. 1953, 5, 103-110
    29. Aumiiller, A.; Hiinig, S. Liebigs Ann. Chem. 1986, 142-164.
    30. Kuhle, E. Angew. Chem. Int. Ed. 1969, 8, 20-34.
    31. Reddy, N. L.; Hu, L.Y.; Cotter, R. E.; Fischer, J. B.; Wong, W. J.; McBurney, B. N.; Weber, E.; Holmes, D. L.; Wong, S .T.; Prasad, R.; John, F. W. K. J. Med. Chem. 1994, 37, 260-267.
    32. Suto, M.J.; Gayo-Fung, L. M.; Palanki, M. S. S.; Sullivan, R. Tetrahedron 1988. 54, 4141-4150.
    33. Lebel, H.; Leogane, O. Org. Lett. 2006, 8, 5717-5720.
    34. Zheng, S.; Li, F.; Liua, J.; Xia, C. Tetrahedron 2007. 48, 5883-5886.
    35. Padiya, K. J.; Gavade, G.; Kardile, B.; Tiwari, M.; Bajare, S.; Mane, M.; Gaware, V.; Varghese, S.; Harel, D.; Kurhade, S. Org. Lett. 2012, 11, 2814-2817.
    36. Wu, Y. Q.; Limburg, D. C.; Wilkinson, D. C.; Hamilton, G. S. Org. Lett. 2000, 2, 795-797.
    37. Yang,Y.; Zhang, Y.; Wang, J. J. Org. Lett. 2011, 13, 5608-5611.
    38. Zhou, L.; Chen, J.; Zhou, J.; Yeung, Y. Y. Org. Lett. 2011, 13, 5804-5807.
    39. Shie, J. J.; Fang, J. M. J. Org. Chem. 2007, 72, 3141-3144.
    40. Larksarp, C.; Alper, H. J. Org. Chem. 1998, 63, 6229-6233.
    41. Bakunov, S. A.; Rukavishnikov, A. V.; Tkachev, A. V. Synthesis 2000, 1148-1159.
    42. Lin, J. B. Design Synthesis and Biological Evaluation of 6-Alkylamino uridine and 6-(1,2,4-Oxadiazol-3-yl)uridine Derivatives; M. Sc. Thesis, National Taiwan Normal University, 2010.
    43. Liao, Y. S. Design Synthesis and Biological Evaluation of 6-Alkylamino uridine and 5-(1,2,4-Oxadiazol-3-yl)uridine Derivatives; M. Sc. Thesis, National Taiwan Normal University, 2010.
    44. Gerfaud, T.; Wei, H. L.; Neuville, L.; Zhu, J. Org. Lett. 2011, 13, 6172-6175.
    45. Hosseinzadeh, R.; Sarrafi, Y.; Mohadjerani, M.; Mohammadpourmir, F. Tetrahedron Lett. 2008, 49, 840-843.
    46. Still, W.C.; Kahn, M.; Mitva, A. J. Org. Chem. 1978, 43, 2923.

    下載圖示
    QR CODE