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Author: 洪紹豪
Hong, Shao-Hao
Thesis Title: 利用膦試劑誘導生成季鏻鹽以合成雙雜環化合物及呋喃[3,2-c]香豆素衍生物
Preparation of Bis-heterocycles and Furo[3,2-c]coumarins via Phosphonium Salt Intermediates
Advisor: 林文偉
Lin, Wen-Wei
Degree: 碩士
Master
Department: 化學系
Department of Chemistry
Thesis Publication Year: 2015
Academic Year: 104
Language: 中文
Number of pages: 550
Keywords (in Chinese): 膦試劑鏻鹽雙雜環化合物呋喃香豆素Wittig 反應
Keywords (in English): phosphine, phosphonium salt, bis-heterocycles, furocoumarin, Wittig reaction
Thesis Type: Academic thesis/ dissertation
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  • 第一章:利用吲哚、水楊醛及醯氯行縮合/醯化/Wittig連鎖反應,在酸以及膦試劑的誘導下可以成功地合成吲哚-苯并呋喃加成物。此反應所需條件十分溫和,不需使用過渡金屬催化,起始物也不需預先處理或活化,為一合成雙雜環化合物的新路徑。反應中所生成的中間體為可簡單分離並純化的穩定季鏻鹽,是一具有潛力的Wittig試劑。

    第二章:利用查耳酮香豆素作為起始物,與膦試劑及醯氯反應後可有效率地得到應用性多元的季鏻鹽中間體,其可加入飽和碳酸氫鈉水溶液切除膦試劑,得到呋喃[3,2-c]香豆素產物;亦可加入鹼及高活性的羰基化合物並進行分子間Wittig反應,得到具有烯烴的呋喃[3,2-c]香豆素產物。此法的反應條件十分溫和,可在短時間內得到預期產物。

    Chapter I: An acid-mediated condensation/acylation/Wittig tandem reaction between indoles, salicylaldehyde dericatives and acyl chlorides to generate indole-benzo[b]furan adducts is described. This highly efficient approach towards such bis-heterocyclic compounds via easily accessible phosphonium salt intermediates has not been reported. Under metal-free reaction conditions and without preactivation of the coupling partners, this synthetic strategy provides the desired products in moderate to good yields in a two-step procedure. Furthermore, we also developed a protocol in a one-pot approach with the only slightly diminished yield of the desired adduct.

    Chapter II: A Bu3P-mediated cyclisation reaction of 3-cinnamoyl-4-hydroxy-2H-chromen-2-ones via electrophilic addition of acyl chlorides towards the synthesis of highly functionalized furo[3,2-c]coumarins bearing a phosphorus ylide moiety is described. These unprecedented cyclisation reactions proceed under mild reaction conditions within short reaction times (1 min to 1 h), and can be further applied in the synthesis of alkenyl-substituted furo[3,2-c]coumarins after the treatment with carbonyl electrophiles under basic condition.

    簡歷 I 謝誌 II 摘要 III Abstract IV 目錄 V 第一章、利用膦試劑誘導吲哚生成季鏻鹽以合成雙雜環化合物 1 1-1前言 1 1-1-1吲哚衍生物 1 1-1-2苯并[b]呋喃衍生物 3 1-2雙雜環化合物合成方法及文獻探討 4 1-2-1偶合反應製備雙環化合物 4 1-2-2吲哚的反應性 9 1-3研究動機 12 1-4實驗結果與討論 14 1-4-1起始物製備 14 1-4-2嘗試合成兩性離子中間體 15 1-4-3利用以對甲苯磺酸作為對離子之季鏻鹽中間體合成多環化合物 19 1-4-4於室溫下合成季鏻鹽 23 1-4-5於室溫下篩選最佳溶劑 25 1-4-6篩選不同膦試劑 26 1-4-7於室溫下篩選最佳化反應條件 30 1-4-8水楊醛之官能基測試與探討 31 1-4-9分子內Wittig合環反應之官能基測試與探討 32 1-4-10一鍋化反應 34 1-4-11反應機制探討 34 1-5結論 35 1-6實驗部分 36 1-6-1分析儀器及基本實驗操作 36 1-6-2實驗操作步驟 38 1-6-3 製備步驟及光譜數據 39 1-7 參考資料 62 第二章、利用膦試劑誘導合成呋喃[3,2-c]香豆素衍生物 64 2-1前言 64 2-2 呋喃[3,2-c]香豆素的合成與文獻探討 66 2-2-1 建構呋喃 66 2-2-2 建構-吡喃酮 70 2-2-3 其他方法 71 2-3研究動機 73 2-4實驗結果與討論 75 2-4-1起始物製備 75 2-4-2首次嘗試合成呋喃香豆素 76 2-4-3最佳化反應條件 77 2-4-4起始物官能基耐受度探討 80 2-4-5醯氯官能基耐受度探討 82 2-4-6同時改變起始物及醯氯的官能基 83 2-4-7重要中間體季鏻鹽的研究 86 2-4-8利用季鏻鹽中間體合成烯烴產物 88 2-4-9最佳化合成烯烴呋喃[3,2-c]香豆素反應條件 89 2-4-10以乙基乙醛酯作為親電試劑的官能基耐受度探討 90 2-4-11以茚三酮作為親電試劑的官能基耐受度探討 92 2-4-12鑑定反應中間體 94 2-4-13設計控制實驗 96 2-4-14設計開環起始物合成四取代呋喃 97 2-4-15反應機制探討 99 2-5結論 100 2-6實驗部分 101 2-6-1分析儀器及基本實驗操作 101 2-6-2實驗操作步驟 103 2-6-3 製備步驟及光譜數據 105 2-7 參考資料 159 附錄1 161 附錄2 333

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