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研究生： 楊心誠
Yang, Shin-Cherng
論文名稱： 氮轉移試劑的反應機制探討與醯胺官能基修飾對其穩定性及化學反應性之影響
Investigation into the Reaction Mechanism of N-Transfer Reagents and the Effect of Amide Functionalization on Its Stability and Reactivity
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： 132
中文關鍵詞： 氮轉移試劑 、重氮鹽 、三氮烯 、重氮化合物
外文關鍵詞： N-transfer Reagent, Diazonium Salt, Diazo Compound , Triazene
相關次數： 點閱：61  下載：5 
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    • 本實驗室開發出一種新穎的第一代氮轉移試劑（N-transfer reagent），為一芳基重氮鹽化合物，可透過重氮官能基的親電性與帶有親核性的氨基酸衍生物進行反應，而後形成三氮烯化合物，並在溫和的鹼性情況下藉由關環驅動力，脫去易離去的4-氟苯酚，形成重氮化合物與內醯胺關環副產物，且都有非常良好的產率表現。整體而言，氮轉移試劑將氮原子轉移至胺基形成重氮化合物，故稱之為氮轉移反應。
    雖然氮轉移反應在本實驗室已經成功應用在多種氨基酸衍生物上形成重氮化合物，但始終還未對氮轉移反應的反應機制進行探討。為了探討反應機制，需要佐以實驗進行驗證。首先，氮轉移反應於反應中會形成三氮烯化合物，但由於關環驅動力過於強烈，在一般的情況下較難進行分離純化。透過增加氨基酸衍生物的立體障礙，使裂解的趨勢大幅下降，成功合成出可穩定存在並進行光譜鑑定的三氮烯化合物。接著，為了探討氮原子轉移的過程，本篇引入15N的氮轉移試劑進行反應，將反應獲得的三氮烯化合物與重氮化合物進行光譜鑑定，證明了氮原子的轉移過程。最後則是藉由核磁共振光譜儀，對三氮烯化合物進行持續的追蹤，觀察三氮烯化合物裂解的過程。透過以上的實驗，我們推論出合理的氮轉移反應機制，有助於我們對氮轉移試劑進行後續的改良。
    第一代氮轉移試劑具有保存不易以及反應初期還原副產物的產生這兩種缺點。於先前實驗室學姊的論文中提出的推/拉電子的官能基修飾，對於第一代氮轉移試劑的缺點有明顯的改善，是為第二代氮轉移試劑，但依然有美中不足的地方。推電子基具有良好的穩定性，但反應性卻有明顯的下降；拉電子基則表現出相反的趨勢，具有優秀的反應性表現，在穩定性上與第一代氮轉移試劑相比卻沒有明顯的進步。本篇透過引入拉電子的醯胺官能基，並利用置換不同的醯胺取代基，適當降低第二代氮轉移試劑拉電子的強度，以期獲得較高的穩定性，在反應性上也能同時表現出拉電子取代基應有的優勢。合成的過程中，透過引入適當的羧酸保護基，使各個官能基可以在不同的反應條件下進行選擇性的反應，最後成功的合成出在氮轉移試劑當中帶有醯胺官能基的重氮鹽化合物。在後續的性質測試中，也如先前所預期的結果，在穩定性上獲得提升，而在反應性上也表現出優秀的產率，可以說是在穩定度與反應性上取得了一個最好的平衡，是目前為止所合成出的第二代氮轉移試劑中表現最為出色的結果。

    Our lab had developed a novel first-generation N-transfer reagent, which reacting with the amino acid derivatives through its electrophilicity of diazonium groups to form the corresponding diazo compound with pleasant yields. Although the N-transfer reaction had been successfully applied to a variety of amino acid derivatives to form diazo compounds, the reaction mechanism of the N-transfer reaction still had not been proposed. To explore the reaction mechanism, Several experiments were done. Through the experiments, we deduced a reasonable mechanism of N-transfer reaction.
    The first-generation N-transfer reagent was difficult to store, and the reduced by-products at the beginning of the reaction needed to be solved. The functional group modification of donating/withdrawing group proposed in the previous dissertation, which was called second-generation N-transfer reagents, could improve the shortcomings of the first-generation N-transfer reagent. However, the electron-donating groups had great stability, but its reactivity was significantly reduced. The electron-withdrawing group showed the opposite tendency. In this dissertation, we introduced electron-withdrawing amide functional groups and replaced different amide substituents, which appropriately reducing the electron-withdrawing strength of the N-transfer reagents to obtain higher stability and maintain reactivity at the same time. In the subsequent tests, the stability was greatly improved, and the reactivity also showed excellent yield, which could be said to be achieved the best balance in stability and reactivity.

    摘要 I 誌謝 VII 目錄 IX 圖目錄 XI 表目錄 XII 流程目錄 XIII 壹、前言 1 1.1 重氮化合物 (Diazo compounds) 1 1.1.1 α-羰基重氮化合物 2 1.1.2 α-羰基重氮化合物的合成 3 1.2 重氮鹽化合物（Diazonium compounds） 5 1.2.1 重氮鹽化合物的應用 6 1.3 三氮烯化合物 （Triazene compounds） 9 1.3.1 三氮烯化合物的應用 9 1.4 研究動機 12 貳、結果與討論 14 2.1 氮轉移試劑的反應機制探討 14 2.1.1 實驗設計與原理 14 2.1.2 合成穩定三氮烯化合物 15 2.1.3 15N-氮轉移反應 17 2.1.4 NMR追蹤三氮烯化合物裂解 20 2.1.5 氮轉移反應的反應機制推測 25 2.2 第二代氮轉移試劑 26 2.2.1 實驗設計與原理 26 2.2.2 在醯胺或羧酸官能基存在下或以耦合反應合成氮轉移試劑 27 2.2.3 以酯類官能基進行保護合成氮轉移試劑 32 2.2.4 第二代氮轉移試劑的物性比較 40 2.2.5 第二代氮轉移試劑的氮轉移反應 44 2.2.6 第二代氮轉移試劑的氮轉移反應速度追蹤 47 參、結論 52 3.1 氮轉移試劑的反應機制探討 52 3.2 第二代氮轉移試劑 52 肆、實驗部分 53 4.1 General Information 53 4.1.1 Materials 53 4.1.2 Methods 53 4.1.3 Machines 53 4.2 Synthesis of Result and Discussion Part I 54 4.3 Synthesis of Result and Discussion Part II 63 伍、參考文獻 82 陸、核磁共振光譜 88

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