用鹼來控制2-(醯基(2-丙炔基)胺基)苯甲醛對甲苯磺醯腙的區域選擇開關反應研究 Investigation of Base Controlled Regioselective Switching Reactions of 2-(acyl(prop-2-yn-1-yl)amino)benzaldehyde tosyl hydrazones

Date
2019
Authors
呂明軒
Lu, Ming-Hsuan
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Abstract
本論文主要分為兩個章節。第一章先簡單介紹有關吡唑、吲哚化合物與區域選擇開關反應,並回顧區域選擇開關反應的相關文獻;此外,本論文主要為甲苯磺醯腙衍生物的相關研究,同時回顧有關甲苯磺醯腙化合物反應的相關文獻。 第二章分為兩個部分。第一部分為甲苯磺醯腙與溫和的鹼作用時的反應探討。在無水的四氫呋喃中,甲苯磺醯腙與碳酸銫作用時可合成具有生物活性的吡唑融合喹啉的衍生物。此反應涉及重氮基與炔類 (與胺連接的丙炔基) 進行分子內1,3-偶極環加成反應;第二部分為甲苯磺醯腙與強鹼作用的反應探討。在無水的四氫呋喃中,甲苯磺醯腙在強鹼 (氫化鈉) 的作用下合成氮-丙二烯基-2,3-二取代吲哚的衍生物。此反應為甲苯磺醯腙在強鹼的存在下,先脫去甲苯磺酸鹽形成重氮中間體,之後有兩種可能的反應途徑,第一種可能為重氮中間體先進行分子內親核加成反應後再進一步脫去氮氣形成環氧乙烷中間體;另一種則是重氮中間體先脫去氮氣形成卡賓中間體,卡賓中間體再和醯胺上的羰基進行反應而產生環氧乙烷中間體。上述反應的中間產物環氧乙烷中間體接著被甲苯磺酸陰離子攻擊而形成2-甲基-1-(2-丙炔基)-3-甲苯磺醯吲哚-2-醇,並進一步脫去水而形成氮-丙炔基-2,3-二取代的吲哚衍生物。此外,甲醇和氫化鈉作用形成甲醇鈉後再與氮-丙炔基-2,3-二取代的吲哚化合物反應產生氮-丙二烯基-2,3-二取代的吲哚衍生物。
This thesis is divided in two chapters. The first chapter includes the introduction to pyrazole, indole compounds and literature survey on the regioseletive switching process. In addition, this thesis is mainly related to the study of tosyl hydrazone derivatives and the detailed survey of literature on reaction of tosyl hydrazones has been described. We then disclosed the aim and research goals at the end of this chapter. The second chapter is subdivided into two parts. The first part is the using mild base (cesium carbonate) to mediate reaction of tosylhydrazone (N-(prop-2-yn-1-yl)-N-(2-((2-tosylhydrazono)methyl)phenyl)acetamide) in dry THF to produce pyrazole fused quinoline (N-acyl-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline) derivatives. This reaction involves intramolecular 1,3-dipolar cycloaddition of diazo group and alkyne (propargyl group attached to amine). The second part focuses on the using strong base such as NaH mediated reaction of tosylhydrazone(N-(prop-2-yn-1-yl)-N-(2-((2-tosylhydrazono)methyl)phenyl) acetamide) in dry THF to produce N-allenyl-2,3-disubstituted indole derivatives. This reaction may involve the generation of diazo intermediate from the tosylhydrazone by the loss of tosylate in the presence of base. This diazo intermediate may produce N-allenyl-2,3-disubstituted indole in two possible reaction pathways. The first one is to undergo intramolecular nucleophilic addition reaction and then followed by the elimination of nitrogen to form an oxirane intermediate, another possibility is to form carbene as intermediate from diazo intermediate by the loss of nitrogen and then to undergo the insertion of carbene to amidic carbonyl to provide oxirane intermediate. Finally, the attack of tosylate to oxirane intermediate afford 2-methyl-1-(prop-2-yn-1-yl)-3-tosylindolin-2-ol and undergo dehydration to afford N-propargyl-2,3-disubstituted indole derivative. Furthermore, the compound N-propargyl-2,3-disubstituted indole upon reacting with in situ generated sodium methoxide to furnish N-allenyl-2,3-disubstituted indole derivative.
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甲苯磺醯腙, 卡賓, 1, 3-偶極環加成反應, 吡唑, 吲哚, tosyl hydrazone, carbene, 1, 3-dipolar cycloaddition, pyrazole, indole
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