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Title: (1)布忍斯特酸催化N-具取代腈胺與芳香胺反應:合成N,N’-二取代胍衍生物 (2)銅催化N-(2-溴苯基)-N’-芳香基胍的合環反應
(1)Synthesis of N,N’-disubstituted guanidine derivatives by Brønsted acid-catalyzed reaction of N-substituted cyanamides with arylamines (2)Copper-catalyzed cyclization reaction of N-(2-bromophenyl)-N’-arylguanidines
Authors: 簡敦誠
Chen, Chia Jung
Keywords: N
copper catalyzed
Tiemann rearrangement
pharmacological activities
Issue Date: 2016
Abstract: 2-苯基胺基苯并咪唑 (2-phenylaminobenzimidazole) 與 N,N’-雙苯基胍基化合物(N,N’-diphenylguanidine) 是常見於擁有藥理活性重要化學骨架的含氮化合物。 含有 benzimidazole 的單元結構的化合物在生物活性上有良好的表現,包括對於抗腫瘤、抗高血壓、抗癲癇以及抗 HIV-1 病毒等方面;而含有苯并咪唑(benzimidazole) 單元結構的藥物,其藥理活性的研究也曾報導於先前的文獻。由於含有此結構的化合物有其重要性,有關它的合成方法一直以來是重要的研究議題。 由於 2-苯基胺基苯并咪唑 (2-phenylaminobenzimidazole) 分子結構可由 N,N’-雙苯基胍基化合物 (N,N’-diphenylguanidine) 進行分子內環化合成,因此我們將報導 (1)苯并咪唑 (benzimidazole) 的前驅物胍基化合物 (guanidine) 的合成研究,以及 (2) 探討苯并咪唑 (benzimidazole) 的合成。在本論文的第一部分的研究中,透過我們團隊先前所發表有效合成腈胺 (cyanamide) 的方法合成苯腈胺 (phenylcyanamide),進一步與含有推拉電子基團的苯胺 (aniline) 在布忍斯特酸 TsOH 的酸性環境下迴流生成N,N’-雙苯基胍基化合物 (N,N’-diphenylguanidine) 化合物,無論是以含推拉電子官能基團 (如 OMe,CH3 與 NO2 等) 的苯腈胺 (phenylcyanamide) 和苯胺 (aniline) 為起始物,在此合成途徑皆可以有不錯的反應性。 在第二部分,我們著重在探討苯并咪唑 (benzimidazole) 的合成。有趣地發現延伸第一部分研究成果,N,N’-雙苯胍基化合物 (N,N’-diphenylguanidine) 可以作為苯并咪唑 (benzimidazole) 的前驅物 2。我們團隊透過先前文獻探討 C-N 鍵生成的報導,以 Buchwald-Hartwig-type reaction、CuCl 為催化劑與 TMEDA 為 ligand 在鹼性條件下合成一系列 2-arylbenzimidazole 化合物。此合成途徑的反應條件相較於其他的合成途徑來得溫和,並且有引入多樣性的官能基,因此可以應用在相關藥物合成與材料合成等。
2-Phenylaminobenzimidazoles and N,N'-diarylguanidines are common nitrogencontaining chemical scaffolds which displayed a wide range of pharmacological activities, such as antitumor, anti-hypertension and anti-HIV-1 virus activities. Therefore, the synthesis of these nitrogen-containing compounds has always been of great interest to organic chemists. 2-Phenylaminobenzimidazoles can be considered as a cyclic form of N,N'-diarylguanidines. Herein, we will discuss their background, importance and synthesis in two major parts. In the first part, our group has recently developed a novel approach for the synthesis of 2-phenylaminobenzimidazoles from benzonitriles and aniline derivatives. A series of benzonitriles were treated with hydroxylamine to afford the amide oximes followed by the Tiemann rearrangement to afford the corresponding N-arylcyanamides. The acid-catalyzed guanidine formation from the reaction of N-arylcyanamides with anilines afforded a series of N,N’-diphenylguanidine-TsOH salts in good yields. The second part, we refer to the N,N’-diphenylguanidines possessed ortho-bromo substituent were subjected to copper(I) chloride-catalyzed intramolecular C-N bond formation to give the desired 2-phenylaminobenzimidazoles. This is an operationally simple procedure that works at moderate condition with good yields and excellent N-regioselectivity. Besides, base on various groups on N,N’-diphenylguanidine could bear this reaction codition, the synthesis could be used to related synthetic drugs and synthetic materials, etc.
Other Identifiers: G060142032S
Appears in Collections:學位論文

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