請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/88218
標題: | 鹵代氟苯與腈類藉由鄰位鋰化驅動 [2+2+2] 串聯環化反應一鍋化合成2,4-雙取代喹唑啉衍生物 Ortho-Lithiation Driven One-Pot Synthesis of 2,4-Disubstituted Quinazolines via [2+2+2] Cascade Annulation of Halofluorobenzenes with Nitriles |
作者: | 薛仁竣 Jen-Chun Hsueh |
指導教授: | 梁文傑 Man-kit Leung |
關鍵字: | 喹唑啉,一鍋化合成,鄰位鋰化,芳香族親核取代反應, Quinazoline,One-pot synthesis,Ortho-lithiation,Nucleophilic aromatic substitution reaction, |
出版年 : | 2023 |
學位: | 碩士 |
摘要: | 喹唑啉在藥物研究上扮演相當重要的角色,在市面上有許多以喹唑啉結構所衍生的藥物用於治療多項疾病,因為此項特性,許多科學家致力於研究如何透過具經濟效益且簡易的方式合成喹唑啉衍生物。在本論文中我們提供了一鍋化合成喹唑啉衍生物的方法,主要講述以含氟苯環與二異丙基胺基鋰反應產生鄰位導向鋰化中間產物,其產生的負電荷可與兩當量的芳香腈進行連續的親核加成反應,最後以氟原子作為離去基進行芳香環親核取代反應得到2,4-雙芳香環取代的喹唑啉衍生物,此方法所使用到的起始物皆可由市面上取得,過程中並無過渡金屬催化劑使用,且簡便的一鍋化合成方式給予了合成喹唑啉衍生物的新途徑。 Quinazoline plays a significant role in pharmaceutical research. Numerous quinazoline-derived drugs are available in the market for treating various diseases. Due to this characteristic, many scientists are dedicated to researching cost-effective and straightforward methods for synthesizing quinazoline derivatives. In this study, we report a one-pot synthesis of quinazoline derivatives from halofluorobenzenes and nitriles. The synthesis involves the reaction of halofluorobenzenes with lithium diisopropylamide to generate a lithiated intermediate that exhibits ortho-selectivity. The resulting aryl lithium undergoes sequential nucleophilic addition with two equivalents of aryl nitriles. Finally, a nucleophilic aromatic substitution reaction occurs with fluoride as the leaving group, resulting in 2,4-diarylquinazoline derivatives. The advantages of this approach are transition metal-free, easy to operate, and all the starting materials are commercially available, providing a new method for synthesizing quinazoline derivatives. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/88218 |
DOI: | 10.6342/NTU202301835 |
全文授權: | 同意授權(全球公開) |
顯示於系所單位: | 化學系 |
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