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研究生： 紀子敬
Chi, Tzu-Ching
論文名稱： 以β酮/醛基磷酸二酯製備1,4-/1,5-二取代和1,4,5-三取代-1,2,3-三唑並探討其反應機構
Regioselective Synthesis of 1,4-/1,5-Disubstituted- and 1,4,5-Trisubstituted-1,2,3-Triazoles with β-Formyl/Keto-phosphonates and Investigation on the Mechanism
指導教授： 周鶴軒
Chou, Ho-Hsuan
學位類別： 碩士
Master
系所名稱： 理學院 - 化學系
Department of Chemistry
論文出版年： 2021
畢業學年度： 109
語文別： 中文
論文頁數： 201
中文關鍵詞： β-酮基磷酸二酯 、二取代-1,2,3 三唑 、三取代-1,2,3 三唑 、無過渡金屬 、立體選擇性
外文關鍵詞： β-ketophosphonate, disubstituted-1,2,3 triazole, trisubstituted-1,2,3 triazole, metal free, regiospecific
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    • 1,4,5-三取代-1,2,3-三唑具備多功能的性質，能夠在五環上同時修飾固定位向的三種特殊官能基，因此能夠有複合的效果，在藥物中十分常見。
    本篇使用非金屬催化方法製備1,2,3-三唑，使用β-酮基磷酸二酯化合物4，在碳酸銫的鹼性下，脫氫後形成4的陰離子再更進一步與銫離子螯合，形成錯合物M’，而此錯合物會限制酮基與磷酯基在同一個位向，避開了反向合環的機會，因此能夠加快與疊氮化物5進行[3+2]合環，高產率且單一的獲得1,4,5-三取代-1,2,3-三唑產物，此種合成方式可以製備出4號位非拉電子基團的三取代三唑，這是過去合成方法較困難的，且延伸至1,4-/1,5-二取代-1,2,3-三唑，能仍保有良好的選擇性與不錯的產率。此外本方法在室溫、弱鹼條件，都相較過去的方法來得溫和，這點在官能基的耐受度上也能夠得到較好的發揮。

    In this thesis, we provided the metal free and mild conditions to synthesize 1,4-/1,5-disubstituted- or 1,4,5-trisubstituted-triazoles to produce good to excellent yields. Under these conditions, 2‐oxopropylphosphonates 4 could be chelated by cesium cation to form intermediate M’. However, we noticed that the chelate effect not only increased the reaction rate of azide-enolate 1,3 dipolar cycloaddition but also inhibited the formation of by-products. Furthermore, we have studied the reaction through 1H / 31P NMR tracking. Based on those obtained results, we have put forward discussion and hypothesis aiming at the plausible mechanisms.

    摘要 I 誌謝 VII 目錄 VIII 表目錄 X 圖目錄 XI 流程目錄 XII 1. 前言 1 1.1. 三唑 (triazole) 1 1.1.1. 1,2,3-三唑化合物之合成方法 2 1.1.2. 1,4,5-三取代-1,2,3-三唑化合物之合成方法 3 1.1.3. 以β-酮基磷酸二甲酯製備1,2,3-三唑之合成方法 4 1.2. β-酮基磷酸二甲酯化合物之合成方法 6 1.3. 研究動機 8 2. 結果與討論 9 2.1. 實驗設計與原理 9 2.2. 含側鏈取代的β-酮基磷酸二酯化合物之製備方法 10 2.2.1. 以阿爾布佐夫反應與親和取代製備β-酮基磷酸二酯化合物 10 2.2.2. 以阿爾布佐夫反應與親核醯基取代反應製備β-酮基磷酸二酯 13 2.2.3. 以1,3-migration製備環狀β-酮基磷酸二酯之方法 15 2.3. 各種疊氮化物之製備方法 16 2.3.1. 疊氮化物之製備方法一 16 2.3.2. 疊氮化物之製備方法二 17 2.4. 探討β-酮基磷酸二酯化合物與疊氮化物之[3+2]合環反應 17 2.4.1. 以對甲苯磺醯疊氮化物作為偶極體 17 2.4.2. 以苯基、烷基疊氮化物作為偶極體 18 2.4.3. [3+2]合環反應之條件優化 19 2.4.4. 討論具備不同官能基的疊氮化物之影響 21 2.4.5. 探討β-酮基磷酸二酯化合物的R1取代對[3+2]反應之影響 22 2.4.6. 探討β-酮基磷酸二酯化合物的R2取代對[3+2]反應之影響 23 2.4.7. 探討製備環狀三取代1,2,3-三唑之反應情形 26 2.4.8. 探討製備1,4-二取代-1,2,3-三唑之反應情形 26 2.4.9. 探討製備1,5-二取代-1,2,3-三唑之反應情形 27 2.4.10. 特殊案例的嘗試 28 2.5. 核磁共振1H, 31P譜追蹤反應 29 2.6. 反應機構探討 35 3. 結論 37 4. 實驗部分 38 4.1. General information 38 4.2. Synthesis of compound 1 39 4.3. General procedure for the synthesis of compound 2, 3 41 4.4. General procedure for the synthesis of compound 4 50 4.5. General procedure for the synthesis of compound 5 66 4.6. General procedure for the synthesis of compound 6 69 4.7. General procedure for the synthesis of compound 7 92 5. 參考文獻 95 6. 核磁共振光譜 99 6.1. 表 十一 核磁共振光譜 186

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