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研究生: 呂依旻
論文名稱: 左旋噻咪唑在外消旋二級醇動力學分割反應之探討與4-二甲基胺基吡啶衍生之新有機催化劑的開發
(−)-Tetramisole in Kinetic Resolution of Racemic Secondary Alcohols and Synthesis of New Organocatalyst Derived 4-(Dimethylamino)pyridine
指導教授: 陳焜銘
學位類別: 碩士
Master
系所名稱: 化學系
Department of Chemistry
論文出版年: 2012
畢業學年度: 100
語文別: 中文
論文頁數: 30
中文關鍵詞: 動力學分割4-二甲基胺基吡啶有機催化劑外消旋二級醇
英文關鍵詞: kinetic resolution, 4-(dimethylamino)pyridine, organocatalyst, racemic secondary alcohols
論文種類: 學術論文
相關次數: 點閱:103下載:1
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  • 掌性2-羥基羧酸酯分子結構,常見於藥物分子及生物活性分子,過去有許多關於二級醇之動力學光學分割的文獻研究,但以2-羥基羧酸酯為起始物的相關探討,卻是付之闕如。本論文探討使用外消旋2-羥基羧酸酯為起始物,以便宜又容易獲得的左旋噻咪唑為光學分割劑(10 mol%)、甲苯為溶劑,添加1.0當量的三乙基胺,以0.6當量的異丁酸酐為醯化試劑,在-75 oC與濃度0.05M的條件下,與2-羥基羧酸酯進行動力學光學分割二級醇反應,得到較好的產率及鏡像超越值。利用之前得到高鏡像選擇性之R-form 2-羥基羧酸酯,經由HPLC圖譜分析,確定本研究回收之起始物是以S-form為主,醯化產物則是以R-form為主。
    另一方面,4-二甲基胺基吡啶衍生催化劑,在外消旋二級醇之動力學光學分割的應用上,有不錯的成果,本研究嘗試修飾已知的催化劑結構,合成具4-二甲基胺基吡啶結構之新有機催化劑,目前的合成策略雖可得到催化劑93,但產率不如預期,期望未來發展新合成策略,提升合成步驟的總產率,得到預期的新有機催化劑。

    Chiral 2-hydroxyalkanoates are frequently important core structures in biologically active and pharmaceutical compounds. Several publications about kinetic
    resolution of racemic secondary alcohols were reported, but rare case used 2-hydroxyalkanoates as the starting materials. In this thesis, the reaction was carried
    out using 2-hydroxyalkanoates 76a (0.05 M) and isobutyric anhydride (0.6 equiv) as starting materials in toluene under -75 oC in the presense of triethylamine (1.0 equiv)
    and (−)-tetramisole (10 mol%) as a catalyst. The absolute stereochemistry of the recovered alcohol and acylated product were determined by the comparison with the
    HPLC and X-ray analyses which were studied in our group.
    In addition, chiral 4-(dimethylamino)pyridine derivatives have been used as efficient catalysts in kinetic resolution of secondary alcohols. Design and synthesis of new organocatalyst by insertion of 4-(dimethylamino)pyridine moiety into known catalyst is an important work. In this study, a new 4-(dimethylamino)pyridine derived
    catalyst 93 was synthesized successfully but in low chemical yield. Further modification of synthetic strategy to improve the result is underway in our group.

    中文摘要 英文摘要 第一章 緒論 1-1 前言   1 1-2 動力學光學分割之介紹   1 1-3 動力學光學分割於二級醇之應用  4 1-4 研究動機  14 第二章 結果與討論 2-1  有機催化劑應用於二級醇動力學光學分割反應  15 2-1-1 外消旋2-羥基羧酸酯之製備與應用  15 2-1-2 溶劑效應  16 2-1-3 添加劑效應  17 2-1-4 鑑定絕對立體化學結構  18 2-1-5 醯化試劑劑量效應  19 2-1-6 醯化試劑效應  20 2-1-7 濃度效應  21 2-1-8 取代基效應  22 2-1-9 掌性HPLC分析  23 2-1-10 反應機構之探討  24 2-1-11 結論  25 2-2 4-二甲基胺基吡啶衍生之新有機催化劑的設計與合成  25 2-3 參考文獻  29

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