臺灣博碩士論文加值系統

無水四氫呋喃作溶劑，正丁基鋰為鹼試劑，將含氟麥卡錫試劑 ((EtO)2P(O)-CFSO2C6H5) 進行去質子反應，獲得含氟膦酸碸 [(EtO)2P(O)CFSO2C6H5]-Li+ 碳陰離子，以此離子作親核性試劑與醛類 (RCHO) 及酮類 (R1C(O)R2) 進行 HWE 烯化反應 (Horner-Wadsworth-Emmon olefination)，製得一系列 1-氟-1-碸基乙烯 (RCH=CFSO2C6H5及R1R2C=CFSO2C6H5) 化合物。此化合物在 -碳上引入碸基 (SO2C6H5) 官能基，在 -碳上置入不同取代基，因碸基容易被轉換成錫基 (SnBu3)，可作為合成含氟生物活性化合物前置體。由於 1-氟-1-碸基烯類化合物具有 E型及 Z 型兩種立體異構物，本實驗透過不同反應條件，藉由鹼試劑正丁基鋰及二異丙基氨基鋰的改變、共溶劑 N, N’- 二羰甲基亞丙基脲 (DMPU) 及金屬離子氯化鋰的添加，嘗試提高單一 E 或 Z 型異構物的比例。實驗結果發現，1-氟-1-碸基烯 (RCH=CFSO2C6H5, R = C6H5, 3-BrC6H4, C6H5CH=CH) 化合物的 E 型異構物比例介於 88 % - 100 %為熱力學產物，產物 (C6H5CH=CH)CH=CF-SO2C6H5分離到 100 % 的E 型異構物；而產物 (CH3)(C2H5)CH=CFSO2C6H5的E/Z異構物比例相同。在製備 (3-BrC6H4)CH=CFSO2C6H5化合物時，若將鹼試劑正丁基鋰 (n-BuLi) 置換成二異丙基氨基鋰 (LDA)，發現Z 型異構物明顯提升 5 %；添加共溶劑 N, N’- 二羰甲基亞丙基脲 (DMPU) 則可提高E 型異構物4 %。對於金屬離子氯化鋰 (LiCl) 的添加，有效提升 (CH3)(C2H5)CH=CFSO2C6H5 產物中 7 % 的 Z 型異構物。但對於 (C6H5)CH=CFSO2C6H5 產物，無論是改變鹼試劑或添加共溶劑及金屬離子，E/Z 異構物比例均無明顯的變化。

Deprotonation of McCarthy reagent (EtO2P(O)CHFSO2C6H5) with n-Butyl lithium in tetrahydrofuran solvent affords [(EtO)2P(O)CFSO2C6H5Ph]-Li+ carbanion as nucleophilic reagent, which reacted with aldehyde (RCHO) or ketones (R1C(O)R2) via HWE (Horner-Wadsworth-Emmon) olefination to synthesize a series of 1-fluoro-1-sulfoneethylene (RCH=CFSO2C6H5and R1R2C=CFSO2C6H5). Those kinds ofcompounds put sulfone (SO2C6H5)functional group at α-carbon, and different of substituted group at β-carbon. Sulfone group (SO2C6H5) are easily toconvert to tin group (SnBu3) which as a precursor tofluorine-containing bioactive compound. In this research, change the base fromn-BuLi to lithium diisopropylamide (LDA), addition of cosolvent N, N'-dicarbonyl methylpropylidene urea (DMPU) or metal ion (LiCl) during the reaction try to achieve the higher E or Z isomer ratio in the prepared compound. The research found that, the thermodynamic adduits of 88 % - 100 % E-isomer are the major productin the synthesis of RCH=CFSO2C6H5 (R = C6H5, 3-BrC6H4, C6H5CH=CH). Only the E-isomer was observed in the preparation of (C6H5CH=CH)CH=CFSO2C6H5. However, the product of (3-BrC6H4)CH=CFSO2C6H5 keeps the same E/Z ratio. change the base from n-BuLi to LDA increases 5 % of Z-isomer. Addition of cosolvent DMPU raises the E-isomers for 4 %, Metal ion (LiCl) promotes 7 % E-isomer for (CH3)(C2H5)C=CFSO2C6H5. For the product of (C6H5)CH=CFSO2C6H5, no effects were observed in the presence ofdifferent base, such as n-BuLi and LDA, addition of DMPU cosolvent orLithium Chloride metal ion.

誌謝 ii
摘要 iii
ABSTRACT iv
表目錄 vii
圖目錄 viii
1. 緒論 1
1.1 研究動機及目的 5
1.2 研究架構及方法 6
2. 文獻回顧 8
2.1 五價膦酸類的合成 8
2.2不對稱四取代乙烯類化合物的合成 9
3. 實驗部分 12
3.1 實驗藥品 12
3.2 實驗儀器及裝置 14
3.3 實驗步驟 16
3.3.1 (EtO)2P(O)CFHSO2C6H5 合成 16
3.3.2 C6H5CH=CFSO2C6H5 合成 16
3.3.3 (BrC6H4)CH=CFSO2C6H5 合成 17
3.3.4 (C6H5CH=CH)CH=CFSO2C6H5 合成 18
3.3.5 (C6H5)2C=CFSO2C6H5 合成 19
3.3.6 (CD3)2C=CFSO2C6H5 合成 20
3.3.7 (CH2)5C=CFSO2C6H5 合成 20
3.3.8 (CH3)(C2H5)C=CFSO2C6H5 合成 21
3.4 (EtO)2P(O)CFHSO2C6H5加入不同影響因素下與苯甲醛反應 22
3.4.1 改變鹼試劑二異丙基氨基鋰 (LDA) 22
3.4.2 加入共溶劑 N, N’- 二羰甲基亞丙基脲 (DMPU) 23
3.4.3 加入金屬離子氯化鋰 (LiCl) 24
3.5 (EtO)2P(O)CFHSO2C6H5 加入不同影響因素下與溴苯甲醛反應 25
3.5.1 改變鹼試劑二異丙基氨基鋰 (LDA) 25
3.5.2 加入共溶劑 N, N’- 二羰甲基亞丙基脲 (DMPU) 25
3.5.3 加入金屬離子氯化鋰 (LiCl) 26
3.6 (EtO)2P(O)CFHSO2C6H5 加入不同影響因素下與甲基乙基酮反應 27
3.6.1 改變鹼試劑二異丙基氨基鋰 (LDA) 27
3.6.2 加入共溶劑 N, N’- 二羰甲基亞丙基脲 (DMPU) 28
3.6.3 加入金屬離子氯化鋰 (LiCl) 29
4. 結果與討論 30
4.1 起始物含氟麥卡錫試劑 (EtO)2P(O)CFHSO2C6H5的合成 30
4.2 (EtO)2P(O)CFHSO2C6H5與醛類 (RCHO) 反應：RCH=CFSO2C6H5的製備 36
4.3 不同鹼試劑、共溶劑及金屬離子對形成 E 及 Z-RCH=CFSO2C6H5異構物立體化學研究 45
4.4 (EtO)2P(O)CFHSO2C6H5與酮類 (R1C(O)R2) 反應製備R1R2C=CFSO2C6H5 53
5. 結論 59
參考文獻 61
附錄 66
自傳 97

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