研究生: |
曾乾哲 ZENG, Cian-Jhe |
---|---|
論文名稱: |
銅金屬催化合成胍與苯併咪唑 Copper-Catalyzed Synthesis of Guanidines and Benzimidazoles |
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: | 2014 |
畢業學年度: | 102 |
語文別: | 中文 |
論文頁數: | 84 |
中文關鍵詞: | 胍 、苯併咪唑 、一價碘化銅 、催化 |
英文關鍵詞: | guanidine, benzimidazole, copper (I) iodide, catalysis |
論文種類: | 學術論文 |
相關次數: | 點閱:200 下載:0 |
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本論文共分為三個部分:第一與第二部分著重在 cyanamide 化合物的合成應用,以合成 guanidine 與 benzimidazole 化合物為目標。第三部分則是以研究基因修飾核苷酸 5-hydroxymethylcytidine 化合物的合成方法為主。
在論文第一部分,我們以苯環上具不同取代基的 N-phenylcyanamide 化合物,在一價碘化銅做為催化劑,Xantphos做為配體,與各種一級與二級胺類化合物進行反應,可以合成出一系列的具有雙取代基的 guanidine 化合物。我們的研究提供一個簡便的方法合成 N-alkyl-N’-arylguanidine 化合物。
論文的第二部分,我們以 o-bromophenylcyanamide 化合物,在一價碘化銅做為催化劑、1,10- phenanthroline 做為配體,和各種一級與二級胺類化合物進行反應,合成環外胺基具取代的 2-aminobenzimidazole 化合物。同時,我們設計一系列中間物反應,證實銅催化合成 2-aminobenzimidazole 化合物的反應機構與區位選擇性。
論文的第三部分,我們由 cytidine 合成醣上具保護基的 5-cyanocytidine 化合物,希望使用 DIBAL 試劑還原 5-位置的 cyano 官能基,合成 5-hydroxymethylcytidine 化合物。雖然成功合成預期產物,但產率並不佳。因此我們更換合成策略,希望在鹼基 cytosine 5-號位置引進乙烯基,進行氧化裂解的方式合成產物。所以我們以 5-iodouracil 化合物做為模型進行,Heck 反應進行碳-碳鍵的生成,並將成功的實驗條件套用至 5-iodocytidine 化合物,亦成功的合成醣上具保護基 (E)-5-(2’-Methoxycarbonylvinyl)cytidine 產物。
This thesis contains three parts: In the first and second parts of the thesis , we
investigated the utilitzation of copper(I) iodide-catalyzed reaction of N-substituted
cyanamides to systhsize a wide variety of N,N’-disubstituted guanidine and
2-aminobenzimidazole derivatives. At the same time, In the third part, the synthetic
approach of an epigenetic DNA base 5-hydroxymethyl-2’-deoxycytidine (5-hmdC),
was studied.
In the first part, N-alkyl-N’-arylguanidines could be effectively synthesized
through the reaction of N-arylcyanamides with various primary and secondary
alkylamines, under the catalysis of copper (I) iodide and xantphos in DMF. This
methodology provides a facile access to versatile N,N’-disubstituted guanidine
derivatives from N-arylcyanamides.
In the second part, the synthesis of 2-aminobenzimidazole derivatives from the
reation of o-bromophenylcyanamides with various primary and secondary
alkylamines, under the catalysis of copper (I) iodide and 1,10-phenanthroline in
1,4-dioxane was reported. This methodology provides a direct access to
2-aminobenzimidazole derivatives. Mechanistic investigation including intermediate
studies helped establish a catalytic cycle and the regiochemistry was addressed based
on the porposed mechanism.
In the last part, sugar-protected 5-cyanocytidine was successfully prepared
from cytidine. The reduction of the 5-cyano group to form 5-hydroxymethylcytidine
achieved only in a very low yield. Although the synthesis of 5-hydroxymethylcytidine,
was accomplished, more efficient synthetic approach is yet to be developed.
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