發展新型態之合成N-O雜環化合物之方法及其應用

Development of New and Novel Protocols for the Synthesis of N-O Heterocycles and their Applications

柴亦芳(Mustafa Jahir Raihan)

指導教授 ： Prof. Ching-Fa Yao

國立臺灣師範大學/理學院/化學系/博士(2011年)

摘要

本論文分為四個章節。第一章節，突顯我們的重點並引發我們研究動機。第二章節，使用[hydroxy(tosyloxy)iodo]benzene (HTIB)並藉由水上反應合成吡喃-異噁唑和異噁唑啉。此兩種化合物在有機合成及藥物合成方面具有重要價值，然而文獻中常使用有毒的有機溶劑及反應時間長，且可應用的受質有限等缺點。我們嘗試克服這些限制，利用水上反應並使用HTIB成功的由α-烯丙氧基和α- 炔丙氧基的苯甲醛肟衍生物合成出吡喃-異噁唑和異噁唑啉。由我們實驗結果及相關文獻報導，去推測出反應機構。第三章節，以新的合成方式，藉由HTIB經由N-O耦合合成異噁唑啉-N-氧化物衍生物。N-O的耦合反應在兩種不同介質中反應會有不同反應，根據實驗結果可推測出其反應機構。利用TCC及NBS這類提供鹵素離子的來源與cyclohexene fused isoxazoline N-oxide衍生物反應，便可使連接環己烯環與異噁唑啉之碳-碳鍵斷裂。環斷裂的原因來自於亞硝基中間產物的發生，關於此環斷裂之研究及反應機構的探討將於第四章作進一步討論。第四章，利用亞硝基與鹼反應去合成新型態之肟類衍生物。

關鍵字:水上反應、色烯-異噁唑化合物、異噁唑啉氮氧化物、鹵素離子

關鍵字

水上反應 ； 色烯-異噁唑化合物 ； 異噁唑啉氮氧化物 ； 鹵素離子

並列摘要

This dissertation is divided into four chapters. Chapter I highlights the facts, those motivated us to pursue the research, presented in this dissertation. Chapter II deals with [hydroxy(tosyloxy)iodo]benzene (HTIB) mediated “on water” synthesis of chromeno-isoxazoles and isoxazolines. Chromeno-isoxazolines and chromeno-isoxazoles are synthetically and medicinally valuable compounds. However, the reported methodologies to access these compounds are plunged either by the usage of toxic solvents, long reaction time and applicable to limited number of substrates. We attempted to overcome these limitations by developing a protocol for HTIB mediated on water synthesis of chromeno-isoxazolines and isoxazoles from α-allyloxy and α-propargyloxy benzaldoxime derivatives. A mechanism for this conversion was postulated on the basis of our experimental outcome and related literature reports. In chapter III, an unprecedented synthesis of isoxazoline N-oxide, via HTIB mediated N-O coupling is described. The effect of the mediums on N-O coupling was studied by carrying out the reaction in homogeneous and heterogeneous mediums. A mechanism was postulated on the basis of the experimental outcomes and the mechanism is supported by the related literatures. On treating the cyclohexene fused isoxazoline N-oxide derivatives with halonium ion sources, TCC and NBS, the C-C bond which connects the isoxazoline with cyclohexene ring was cleaved. The ring cleavage is happened via a nitroso intermediate. Scope of this ring cleavage protocol, mechanistic study, and thermal effect on the life time of the nitroso intermediate are discussed in chapter IV. This chapter also deals with the treatment of the nitroso intermediate with a base, to synthesize novel types of oxime derivatives.

Keywords:on water、chromeno-isoxazole、isoxazoline N-oxide、halonium ion

並列關鍵字

on water ； chromeno-isoxazole ； isoxazoline N-oxide ； halonium ion

參考文獻

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