臺灣博碩士論文加值系統

三氯化磷 (PCl3) 與 2,2,2-三氟乙醇 (CF3CH2OH) 進行酯化反應製得雙(2,2,2-三氟乙基)亞磷酸酯 ((CF3CH2O)2P(O)H) 化合物。接著在 -42 oC條件下，(CF3CH2O)2P(O)H與氫化鈉 (NaH) 反應而製備出 (CF3CH2O)2P(O)-Na+ 陰離子做為親核性試劑，此離子與溴乙酸乙酯 (BrCH2CO2Et) 於15 oC下經由 Michaelis-Becker 反應製備出乙基[二(2,2,2-三氟乙氧基)氧膦基]乙酸 ((CF3CH2O)2P(O)CH2CO2Et) 化合物，透過核磁共振光譜儀 (1H, 13C, 19F, 31P NMR)，元素分析儀 (Elementary Analysis, EA)，高解析度質譜儀 (High Resolution Mass, HMRS) 鑑定確立其結構式。以乙基[二(2,2,2-三氟乙氧基)氧膦基]乙酸 ((CF3CH2O)2P(O)CH2CO2Et) 為起始物，四氫呋喃 (THF) 為溶劑，正丁基鋰 (n-BuLi) 為鹼性試劑，在 - 78oC 條件下進行去質子化反應 (Deportonation)，形成 [(CF3CH2O)2P(O)CHCO2Et]-Li+ 中間體後，再分別與醛類 (RCHO) (R = C6H5CH=CH, 3,4-F2C6H3, 3-BrC6H4) 及酮類 (3-CF3C6H4)C(O)(CH3) 進行 Horner-Wadsworth-Emmons (HWE) 反應，獲得一系列 (E,Z)- RCH=CHCO2Et 及 (E,Z)- (3-CF3C6H4)(CH3)C=CHCO2Et 化合物。此化合物之特性是在 α 碳上位置引入酯基 (CO2Et) 官能基，同時在 β 位置的碳上可置入多種不同的取代基。本研究並藉由不同的影響因子，如添加共溶劑六甲基磷醯胺 (Hexamethylphosphoramide, HMPA) 與N,N’ - 二羰甲基亞丙基脲 (N,N’ - Dimethylpropyleneurea, DMPU) 或加入金屬離子(LiCl) 於反應混合液中，嘗試控制產物之順反異構物比例。從實驗結果可發現，(E,Z)-RCH=CHCO2Et 化合物中，加入 HMPA 有助於提升 (E)-異構物比例，加入 DMPU 對異構物比例無明顯影響，而加入 LiCl 能提升產物中(E)-異構物至90 % 以上。
關鍵詞: Michaelis-Becker 反應、HWE 反應、共溶劑、金屬離子。

Esterification of phosphorus trichloride (PCl3) with 2,2,2-trifluoroethanol (CF3CH2OH) gives bis(2,2,2-trifluoroethyl)phosphate ((CF3CH2O)2P(O)H). Treat- ment of (CF3CH2O)2P(O)H with sodium hydride under -42oC gives (CF3CH2O)2P(O)-Na+ carbanion. Reaction of (CF3CH2O)2P(O)-Na+ anion with ethyl bromoacetate (BrCH2CO2Et) at 15oC via Michaelis-Becker reaction affords ethyl [bis(2,2,2)trifluoroethoxy)phosphinyl] acetate ((CF3CH2O)2P(O)CH2CO2Et) which the structure was confirmed by 1H NMR, 13C NMR, 19F NMR, 31P NMR, Elementary Analysis (EA) and High Resolution Mass (HRMS). Deprontonation of starting material ((CF3CH2O)2P(O)CH2CO2Et) with n-butyl lithium (n-BuLi) under -78oC in tetrahydrofuran (THF) provides [(CF3CH2O)2P(O)CH2CO2Et]-Li+ anion. Subsequently reactions of [(CF3CH2O)2P(O)CH CO2Et]-Li+ anion with aldehydes (RCHO) (R = C6H5CH=CH, 3,4-F2C6H3, 3-BrC6H4) and ketones (3-CF3C6H4)C(O)- (CH3) via Horner-Wadsworth-Emmons (HWE) reaction give the vinyl compounds (E,Z)-RCH=CHCO2Et and (E,Z)-(3-CF3C6H4)(CH3)C=CHCO2Et respectively. The prepared vinyl compounds which put the ester group at α-carbon postion and different substituents at β-carbon position act as the precursors to the bioactive compounds. The stereoselectivity of the products depend on the cosolvents (Hexamethylphosphoramide (HMPA) and (N,N’ - Dimethylpropyleneurea (DMPU)) and metal ion (LiCl) presented in the reaction mixture. Experimental results show that in the presence of HMPA, the ratios of (E)-RCH=CHCO2Et increase obviously. Cosolvent DMPU have little effect on the E/Z ratio. In the presence of LiCl, the ratios of (Z)-RCH=CHCO2Et over 90% were observed.
Keywords ： Michaelis-Becker reaction, Horner-Wadsworth-Emmons reaction, Cosolvent, Metel Ion.

誌謝 ii
摘要 iii
ABSTRACT iv
目錄 v
表目錄 viii
圖目錄 ix
1. 緒論 1
1.1研究動機及目的 1
1.2研究架構及方法 2
2. 文獻回顧 4
2.1 五價磷的合成 4
2.2 Michaelis-Becker 試劑合成 5
2.3 乙烯類化合物的合成 6
3. 實驗 10
3.1 實驗藥品 10
3.2 實驗儀器 11
3.3 實驗步驟 12
3.3.1 (CF3CH2O)2P(O)H 合成 12
3.3.2 (CF3CH2O)2P(O)CH2CO2Et 合成 12
3.3.3 (C6H5CH=CH)CH=CHCO2Et 合成 13
3.3.4 (3,4-F2C6H3)CH=CHCO2Et 合成 14
3.3.5 (3-CF3C6H4)C(CH3)=CHCO2Et 合成 15
3.3.6 (3-BrC6H4)CH=CHCO2Et 合成 15
3.4 (CF3CH2O)2P(O)CH2CO2Et 在不同條件下與反式肉桂醛反應 17
3.4.1 加入共溶劑六甲基磷醯胺 (HMPA) 17
3.4.2加入共溶劑N,N’ - 二羰甲基亞丙基脲 (DMPU) 17
3.4.3 加入金屬離子氯化鉀 (LiCl) 18
3.5 (CF3CH2O)2P(O)CH2CO2Et 在不同條件下與3,4-二氟苯甲醛反應 19
3.5.1 加入共溶劑六甲基磷醯胺 (HMPA) 19
3.5.2 加入共溶劑N,N’ - 二羰甲基亞丙基脲 (DMPU) 20
3.5.3 加入金屬離子氯化鉀 (LiCl) 21
3.6 (CF3CH2O)2P(O)CH2CO2Et 在不同條件下與間三氟甲基苯乙酮反應 21
3.6.1 加入共溶劑六甲基磷醯胺 (HMPA) 21
3.6.2 加入共溶劑N,N’ - 二羰甲基亞丙基脲 (DMPU) 22
3.6.3 加入金屬離子氯化鉀 (LiCl) 23
3.7 (CF3CH2O)2P(O)CH2CO2Et 在不同條件下與3-溴苯甲醛反應 24
3.7.1 加入共溶劑六甲基磷醯胺 (HMPA) 24
3.7.2 加入共溶劑N,N’ - 二羰甲基亞丙基脲 (DMPU) 24
3.7.3 加入金屬離子氯化鉀 (LiCl) 25
4. 結果與討論 27
4.1 起始物含氟磷酸酯類 (CF3CH2O)2P(O)CH2CO2Et 的合成 27
4.2 (CF3CH2O)2P(O)CH2CO2Et 與醛類反應： RCH=CHCO2Et製備 30
4.3 共溶劑與金屬離子對形成 (E,Z)-RCH=CHCO2Et 異構物立體化學研究 35
4.4 (CF3CH2O)2P(O)CH2CO2Et 與酮類反應：(3-CF3C6H4)(CH3)C=CHCO2Et 41
製備 41
5. 結論 45
參考文獻 46
附錄 50
自傳 75

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