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論文名稱(中文) 醌類衍生物經由自由基反應與親電性反應合成吖啶類與吖庚因類化合物之研究
論文名稱(英文) Synthesis of Acridines and Azepines from 1,4- Quinone Derivatives via Free Radical Reaction and Electrophilic Reaction
校院名稱 成功大學
系所名稱(中) 化學系
系所名稱(英) Department of Chemistry
學年度 105
學期 2
出版年 106
研究生(中文) 謝昌佑
研究生(英文) Chang-You Sie
學號 L36044228
學位類別 碩士
語文別 中文
論文頁數 105頁
口試委員 指導教授-莊治平
口試委員-吳天賞
口試委員-王志鉦
中文關鍵字 硝酸銀  碸基自由基  吖啶  苯并吖庚因 
英文關鍵字 silver(I) nitrate  sulfonyl radical  acridine  benzazepine 
學科別分類
中文摘要 自由基反應在現今受到重視並且被廣泛地利用於有機合成中,其中利用自由基與不飽和鍵作用並進一步做環化反應的合成方法十分常見。在本篇論文中將使用催化劑量硝酸銀(I)搭配過硫酸鉀水溶液來氧化對甲苯亞磺酸鈉鹽生成碸基自由基,並與2-[(2’-乙炔基)苯胺基]-1,4-萘醌類化合物上的不飽和鍵作用,接著進行分子內環合反應生成吖啶類化合物。在反應中意外發現苯并吖庚因類化合物的生成,故而又將反應拆分為兩個步驟,藉此來合成苯并吖庚因類化合物,根據合成之化合物的不同,將此篇論文分為兩個部分:
英文摘要 SUMMARY
The methods which use free radicals for cyclization reaction can be found in many literatures. Herein we used sulfonyl radical with the compounds that contain triple bond in the presence of silver(I) nitrate and potassium persulfate via the oxidative free radical cyclization reaction to synthesis benzo[b]acridine derivatives. Surprisingly, we found that azepine derivatives were produced as the by-products under certain conditions. So we divided the reaction into two steps to synthesis benzo[b]naphtho[2,3-f]azepine derivatives alone.
Keywords: silver(I) nitrate; sulfonyl radical; acridine; benzazepine.


INTRODUCTION
The skeleton of acridine has been vary attention because it has a good biological activity and pharmacological activity. Acridines can often be found in the drugs as antibacterial, anticorrosion and anticancer, since they have a planar structure and the nitrogen atom is able to interact with base pairs in DNA or RNA readily. Dibenzazepine is a fused tricycles structure, and it is an intermediate for the synthesis of anticonvulsants and antidepressants. In many tricyclic antidepressants (TCAs) we can found the skeleton of acridine as the core.
Free radical reaction is an important synthetic method. Due to the radical intermediates have high activity and the reaction has regio- and stereo-selectivity, the literatures which use free radicals to do the cyclization reaction have been published in a large number. Our laboratory had also published the researches that use silver(II), copper(II), manganese(III) or cerium(IV) to generate oxidative radicals to do the free radical reactions. Silver(II) ion is unstable and expensive, so it is usually generated by catalytic amount of silver(I) nitrate and potassium persulfate. With the rise of environmental awareness, reducing the solvent and catalyst is the direction of efforts, so the use of catalytic amount of silver reagent will be better than the other metal ions.
In this thesis, we divided the content into two parts according to the product of the synthesis. The first part is mediated by sulfonyl radical to do the oxidative radical cyclization reaction to synthesis benzo[b]acridine derivatives. The second part is the synthesis of benzo[b]naphtho[2,3-f]azepine derivatives by electroplic reaction and radical addition reaction.


RESULTS AND DISCUSSION
In the first part, we used catalytic amount of silver(I) nitrate with potassium persulfate aqueous solution to oxidize p-toluenesulfinate sodium salt (TsNa) to generate the sulfonyl radical. The sulfonyl radical interacts with the unsaturated triple bond on 2-(2-ethynylphenylamino)naphthalene-1,4-diones and undergo an intramolecular cyclization reaction to form benzo[b]acridine derivatives. We used the optimized reaction condition to synthesis the methyl substited or halogen substited compounds and achieved good yields. The other hand, we got the unexpected by-product, benzo[b]naphtho[2,3-f]azepine derivatives, in the specific condition.

In the second part, we divided the reaction of the first part into two steps to get 12,13-ditosyl-12,13-dihydro-5H-benzo[b]naphtho[2,3-f]azepine-6,11-diones. Initially, we only added silver(I) nitrate to catalyze the electrophilic cyclization reaction to form 5H-benzo[b]naphtho[2,3-f]azepine-6,11-diones. In this step, methyl substited or halogen substited compounds had high yields, but the electron-withdrawing group would decrease the yields. In the second step, TsNa and potassium persulfate were added to carry out free radical addition reaction to obtain 12,13-disubstituted benzo[b]naphtho[2,3-f]azepine compounds, and in this reaction no matter the electron-donating group, the electron-withdrawing group or halogen didn't affect the yields of the reaction.


CONCLUSION
The synthesis of benzo[b]acridine derivatives and benzo[b]naphtho[2,3-f]azepine derivatives can have good results in this research. The catalytic amount of silver(I) nitrate is used to oxidize TsNa to generate sulfonyl radicals in the first part and catalyze the electrophilic cyclization reaction in the second part. The rate of ionic reaction is significantly slower than the free radical reaction, so the reaction conditions must be divided into two steps to obtain benzo[b]naphtho[2,3-f]azepine derivatives, and compared with the previous examples of the laboratory, the use of silver(I) nitrate catalyst can get better results than Au(III) or Ce(IV).
論文目次 一、 前言……………………………………………………………………1
二、 研究背景與動機
第一節 吖啶類衍生物的合成…………………………………………5
第二節 苯并吖庚因類化合物之合成…………………………………10
第三節 碸基自由基的介紹……………………………………………13
三、 結果與討論
第一章 使用銀(I)催化生成碸基自由基進行氧化性自由基環合反應合成吖啶類化合物……………………………………………………17
第一節 2-碘基苯胺類化合物之合成………………………………….20
第二節 2-苯乙炔基苯胺類化合物之合成……………………………22
第三節 2-乙炔基苯胺類化合物之合成………………………………24
第四節 2-[(2’-苯乙炔基)苯胺基]-1,4-醌類化合物之合成…………27
第五節 2-[(2’-乙炔基)苯胺基]-1,4-醌類化合物之合成……………30
第六節 9-苯甲醯基吖啶類化合物之合成……………………………34
第七節 12-對甲苯磺醯基苯并吖啶類化合物之合成………………38
第二章 以硝酸銀(I)催化進行親電性反應合成苯并吖庚因類化合物…44
第一節 苯并吖庚因類化合物之合成…………………………………44
第二節 12,13-二對甲苯磺醯基苯并萘吖庚因類化合物之合成……50
第三節 以金(III)催化2-[(2’-苯乙炔基)苯胺基]-1,4-醌類化合物合成五元環化合物…………………………………………………55
四、 實驗部分……………………………………………………………….58
(1) 2-乙炔基苯胺類化合物91與1,4-萘醌化合物20進行加成反應的一般步驟…………………………………………………………59
(2) 2,3-二甲基-5-[(2’-苯乙炔基)苯胺基]-1,4-苯醌類化合物95的氧化性自由基環合反應之一般步驟…………………………………66
(3) 2-[(2’-乙炔基)苯胺基]-1,4-萘醌類化合物78與對甲苯亞磺酸鈉鹽與硝酸銀(I)的氧化性自由基反應之一般步驟…………………70
(4) 2-[(2’-乙炔基)苯胺基]-1,4-萘醌類化合物78與硝酸銀(I)進行親電性環合反應之一般步驟…………………………………………74
(5) 苯并萘吖庚因類化合物113與對甲苯亞磺酸鈉鹽與硝酸銀(I)的氧化性自由基反應之一般步驟…………………………………78
(6) 2,3-二甲基-5-[(2’-苯乙炔基)苯胺基]-1,4-苯醌類化合物95與氯金酸鈉進行親電性環合反應之一般步驟…………………………85
參考資料……………………………………………………………………89
1H、13CNMR光譜資料………………………………………………………92
表一 經碘化反應合成2-碘基苯胺類化合物81………………………20
表二 經薗頭耦合反應合成2-苯乙炔基苯胺類化合物84……………22
表三 經薗頭耦合反應合成2-三甲基矽乙炔基苯胺類化合物90……24
表四 2-乙炔基苯胺化合物91的合成反應…………………………25
表五 經1,4-加成合成2-[(2’-苯乙炔基)苯胺基]-1,4-萘醌類化合物76..27
表六 經1,4-加成合成5-[(2’-苯乙炔基)苯胺基]-1,4-苯醌類化合物95..28
表七 經1,4-加成合成2-[(2’-乙炔基)苯胺基]-1,4-萘醌類化合物78…..30
表八 2-[(2’-三甲基矽乙炔基)苯胺基]-1,4-萘醌類化合物101的合成...32
表九 2-[(2’-乙炔基)苯胺基]-1,4-萘醌化合物78的合成………………32
表十 經1,4-加成合成5-[(2’-乙炔基)苯胺基]-1,4-苯醌類化合物102…33
表十一 12-苯甲醯基苯并吖啶類化合物77之反應條件優化…………34
表十二 9-苯甲醯基吖啶類化合物103的合成…………………………….36
表十三 12-對甲苯磺醯基苯并吖啶類化合物79之反應條件優化………38
表十四 12-對甲苯磺醯基苯并吖啶類化合物79之合成………………40
表十五 不同溶劑對合成苯并萘吖庚因類化合物113之影響……………45
表十六 經由親電性環合反應合成苯并萘吖庚因類化合物113………….46
表十七 經由親電性環合反應合成二苯并吖庚因類化合物114………….47
表十八 12,13-二對甲苯磺醯基苯并萘吖庚因類化合物108之反應條件優化…………………………………………………………………...50
表十九 12,13-二對甲苯磺醯基苯并萘吖庚因類化合物108的合成….…51
表二十 12,13-二對甲苯磺醯基苯并萘吖庚因類化合物 108b的合成..…52
表二十一 10,11-二對甲苯磺醯基二苯并吖庚因類化合物117的合成...53
表二十二 以金(III)催化合成五元環化合物122………………………...56
表二十三 以金(III)催化合成五元環化合物123……………………...…56
流程一 吖啶類衍生物的合成文獻回顧……………………………..…….7
流程二 對甲苯亞磺酸鈉鹽於醋酸中生成碸基自由基…………....…….15
流程三 2-[(2’-苯乙炔基)苯胺基]-1,4-萘醌類化合物76的逆合成路徑...18
流程四 2-[(2’-乙炔基)苯胺基]-1,4-萘醌類化合物78的逆合成路徑..…19
流程五 2-碘基苯胺類化合物之合成反應機構……..……..…………..…21
流程六 2-苯乙炔基苯胺類化合物之合成反應機構……………………..23
流程七 2-三甲基矽乙炔基苯胺化合物90的去保護基反應之反應機構.26
流程八 2-[(2’-苯乙炔基)苯胺基]-1,4-醌類化合物之合成反應機構……29
流程九 9-苯甲醯基吖啶類化合物之合成反應機構……………………..37
流程十 苯并吖庚因類化合物之合成反應機構……………….....………49
流程十一 12,13-二對甲苯磺醯基苯并萘吖庚因類化合物108之合成反應機構………………………………………………………….54
流程十二 以金(III)催化合成五元環化合物123之反應機構…………...57
圖一 化合物108b之X-ray單晶繞射結構圖……………………………54

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