[[alternative]]Catalyst-free synthesis of 1,5-Benzodiazepines by cyclocondensation of β,γ-unsaturated ketones with o-phenylenediamine

碩士[[abstract]]苯二氮䓬類化合物是一含雜環結構的化學分子，近年來因具有高度的生物活性而漸漸受到重視；如抗憂慮,抗抑鬱,抗發炎,抗病毒,抗愛滋病和抗微生物等等。以往文獻中苯二氮䓬類化合物合成製備多需利用催化劑來催化反應。因此我們嘗試開發無催化劑反應條件來合成1,5-苯二氮䓬類。我們實驗室以醛類化合物在金屬鎂與丙烯基溴進行超音波促進巴比艾爾反應形式加成得到丙烯基醇，加入氧化劑PCC將丙烯醇氧化成丙烯酮，更進一步與鄰苯二胺進行環化反應得到1,5-苯二氮䓬類。[[abstract]]The benzodiazepines have attracted much attentions as pharmacophoric scaffold of heterocycles with a wide range of biological applications. These compounds are served as potentially biological compound with antianxiety, anti-depress, anti-inflammatory, anti-viral, anti-HIVand anti-microbial activities.Many synthetic methods for benzodiazepines have been reported,and mostly with the introduction of catalyst. We developed a novel catalyst-free method synthetic of 1,5-benzodiazepines which was obtained under sonochemical Barbier-type reaction conditions. A reation mixture of activated magnesium powder, allyl bromide and aldehyde was sonicated to genterate allyl alcohol, followed by treatment of PCC to oxidize the allyl alcohol to allyl ketone.The cyclocondensation reaction of allyl ketone with o-phenylenediamine can produce 1,5-Benzodiazepines.[[tableofcontents]]第一章 緒論.…………………………………………………………..1 1-1 苯二氮䓬化合物及其衍生物的重要性……………………3 (1) 抗腫瘤活性……………………………………………..9 (2) 抗炎性………………………………………................12 (3) 抗菌活性………………………………………………16 1-2 苯二氮䓬的合成方法……………………………....……..22 (1) 酮與鄰苯二胺合成1,5-苯二氮䓬….............................23 (2) 多成分反應合成1,5-苯二氮䓬…………………….…28 (3) α,β-不飽和酮與鄰苯二胺合成1,5-苯二氮䓬……..…32 第二章 結果與討論…………………………………………………....35 2-1 超音波在有機合成上的應用……………………...……...35 (1) 超音波的物理與化學現象…………………………...35 (2)一般實驗室使用的超音波…………………...………..37 2-2 反應條件與結果…..……...……………...…………....…...40 2-3 反應機構的探討……………………………………...……..64 第三章 實驗與儀器………………………………………….…..….....68 3-1 實驗方法…………………………………………………….68 3-2溶劑的乾燥………………………………………..……...….70 3-3 實驗儀器與測試方法……………………………........…….72 第四章 總結…………………………………………………....…...….74 第五章 光譜……………………………………………………………77 第六章 參考資料……………………………………………..………..87 圖表目錄 圖一………………………........................................................................3 圖二…………………………....................................................................4 圖三………………………………………................................................4 圖四………………………........................................................................5 圖五………………....................................................................................6 圖六…………………………....................................................................6 圖七………………....................................................................................7 圖八………………………........................................................................8 圖九………………....................................................................................8 圖十……………………............................................................................8 圖十一…..…………………......................................................................8 圖十二…..…………………......................................................................8 圖十三…..………………..........................................................................8 圖十四………………................................................................................9 圖十五…..…………………......................................................................9 圖十六…..………………………............................................................10 圖十七…..…………………..................................................................10 圖十八…..…………………....................................................................10 圖十九…..………………………............................................................11 圖二十…..…………………………........................................................14 圖二十一.…………………….................................................................14 圖二十二..…………………………........................................................14 圖二十三…………………......................................................................14 圖二十四………………………………..................................................15 圖二十五…………………......................................................................15 圖二十六…………………......................................................................16 圖二十七……………………..................................................................17 圖二十八……………………..................................................................17 圖二十九………………………………..................................................20 圖三十…..………………………………................................................21 圖三十一………………………………..................................................21 圖三十二………………………………..................................................22 圖三十三………………………………..................................................24 圖三十四………………………………..................................................25 圖三十五………………………………..................................................26 圖三十六………………………………..................................................27 圖三十七………………………………..................................................29 圖三十八..................................................................................................30 圖三十九……………………..................................................................31 圖四十…..………………………………................................................31 圖四十一………………………………..................................................32 圖四十二………………………………..................................................33 圖四十三…………………......................................................................34 圖四十四……………………………….................................................38 圖四十五……………………………......................................................38 圖四十六………………………..............................................................38 圖四十七………………………………..................................................39 圖四十八………………………………………………..........................39 圖四十九………………………………..................................................40 圖五十………………………………......................................................41 圖五十一..…………………………........................................................42 圖五十二..…………………………........................................................43 圖五十三..…………………………........................................................43 圖五十四..…………………………........................................................43 圖五十五..……………………................................................................44 圖五十六..…………………………........................................................44 圖五十七..…………………....................................................................45 圖五十八..…………………....................................................................45 圖五十九..…………………………........................................................46 圖六十..…………………………............................................................47 圖六十一.……………………….............................................................47 圖六十二.……………………….............................................................48 圖六十三.……………………….............................................................49 圖六十四.………………….....................................................................53 圖六十五.…………………….................................................................53 圖六十六.……………………….............................................................63 圖六十七.……………………….............................................................64 圖六十八.……………………….............................................................65 圖六十九.……………………….............................................................66 圖七十…..………………………............................................................66 圖七十一.……………………….............................................................67 表一……………………………………………….…………………….51 表二…………………………………….……………………………….54 表三……………………………………………………….…………….57 表四…………………………………….……………………………….59 表五………………………………………….………………………….60 表六……………………………………………….…………………….61[[note]]學號: 601160590, 學年度: 10