本文選題：喹啉N-氧化物化合物　切入點(diǎn)：烷氧基化　出處：《鄭州大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

【摘要】：由于高的原子經(jīng)濟(jì)性,近些年通過碳?xì)浠罨l(fā)展的新的合成方法層出不窮。碳-雜鍵的構(gòu)建更是在有機(jī)合成領(lǐng)域占據(jù)重要地位,因而通過碳?xì)浠罨瘉順?gòu)建碳-雜原子的方法被廣泛報(bào)道,但值得強(qiáng)調(diào)的是,目前所報(bào)道的碳?xì)浠罨姆椒ㄍǔＧ闆r下是在金屬,甚至是貴金屬或有毒金屬的催化作用下進(jìn)行的,而更加綠色的非金屬參與的通過C-H活化來構(gòu)建碳-雜鍵的方法還鮮有報(bào)道,非金屬參與的喹啉C-O鍵的構(gòu)建報(bào)道更少。喹啉作為一類非常重要的藥效基團(tuán),廣泛存在于天然產(chǎn)物和很多市售藥物之中,但喹啉類藥物2位在體內(nèi)極易被氧化而使其失去藥效,因而對喹啉2-位取代衍生物的合成改造具有重要意義。另外,α-烷氧基喹啉及其衍生物是有機(jī)合成重要的中間體結(jié)構(gòu),在農(nóng)業(yè)和藥物化學(xué)領(lǐng)域等展現(xiàn)出其廣泛的物理、化學(xué)及生物活性,因而,探索無金屬條件下通過碳?xì)浠罨姆椒ňG色快速合成α-烷氧基喹啉衍生物的新型合成方法具有重要現(xiàn)實(shí)意義。目前報(bào)道的合成α-烷氧基喹啉和α-芳氧基喹啉的方法主要有:(1)醇或者酚對α-鹵代物親核取代反應(yīng)而得到;(2)磺酰氯等活化基團(tuán)下,喹啉N-氧化合物和醇鈉或者酚鈉進(jìn)行親核加成而得到;(3)通過鄰芳炔異氰化物關(guān)環(huán)脫氫得到。這些已報(bào)道方法的顯著缺點(diǎn)包括:反應(yīng)起始物難以制備、反應(yīng)時(shí)間長、需金屬催化、反應(yīng)條件苛刻等等。本論文發(fā)展了一種在無金屬參與下,以喹啉N-氧化物和醇(酚)為反應(yīng)底物,由普通H-亞磷酸酯參與碳?xì)浠罨目焖俑咝Ш铣?-烷氧基喹啉衍生物的新方法。與以往報(bào)道的方法相比,該方法的顯著優(yōu)勢包括:快速高效、條件溫和、無金屬、原子經(jīng)濟(jì)性好、底物適用性廣泛等。在機(jī)理研究方面,通過核磁磷譜跟蹤方法對實(shí)驗(yàn)機(jī)理進(jìn)行了深入的探討,詳細(xì)闡明了相關(guān)實(shí)驗(yàn)機(jī)理。本論文主要研究內(nèi)容如下:1、對喹啉類化合物的研究進(jìn)展和應(yīng)用情況進(jìn)行了概括總結(jié)。2、以正丙醇和喹啉N-氧化物作為模板反應(yīng),H-亞磷酸酯種類及其用量、反應(yīng)物的用量、堿的種類及其用量、溶劑、四氯化碳用量、反應(yīng)時(shí)間、反應(yīng)溫度等幾個(gè)方面進(jìn)行實(shí)驗(yàn)條件的優(yōu)化,得到了最佳反應(yīng)條件:0.4mmol喹啉N-氧化物,2mmol的正丙醇,0.8mmol的H-亞磷酸二異丙酯,2equiv的二異丙基乙胺,0.5m L四氯化碳,置于3m L的乙腈溶劑之中,常溫?cái)嚢璺磻?yīng)5個(gè)小時(shí)。3、在最優(yōu)反應(yīng)條件下,考察模板反應(yīng)的反應(yīng)底物適用性。此方法廣泛適用于醇、酚及帶不同取代基的喹啉N-氧化物和異喹啉N-氧化物,共合成了目標(biāo)產(chǎn)物26個(gè),結(jié)構(gòu)均經(jīng)過1H NMR、13C NMR、HR MS等數(shù)據(jù)確認(rèn)。4、結(jié)合31P NMR跟蹤實(shí)驗(yàn)對實(shí)驗(yàn)機(jī)理進(jìn)行了闡述
[Abstract]:Because of the high atomic economy, new synthesis methods developed by hydrocarbon activation are emerging in recent years, and the construction of carbon-heterogeneity bonds plays an important role in the field of organic synthesis. Therefore, the method of constructing carbon-hetero atoms through hydrocarbon activation has been widely reported, but it is worth emphasizing that the methods of hydrocarbon activation currently reported are usually carried out under the catalysis of metals, even precious metals or toxic metals. However, there are few reports of greener nonmetallic participation in C-H activation to construct carbon-heterogeneity bonds, and less on nonmetallic quinoline C-O bonds. Quinoline is a very important group of active groups. It is widely found in natural products and many marketable drugs. However, quinoline drugs are easily oxidized in vivo, causing them to lose their efficacy. In addition, 偽 -alkoxy quinoline and its derivatives are important intermediates in organic synthesis. Chemical and biological activity, therefore, It is of great practical significance to explore a new method for the rapid synthesis of 偽 -alkoxy quinoline derivatives by hydrocarbon activation under metal-free conditions. The formulas for the synthesis of 偽 -alkoxy quinoline and 偽 -aryl quinoline reported at present are of great practical significance. The method mainly consists of 1: 1) alcohol or phenol for nucleophilic substitution of 偽 -halogenates to obtain 2) sulfonyl chloride and other active groups. Quinoline N-oxide compounds are synthesized by nucleophilic addition with sodium alcohol or sodium phenolic acid) obtained by ring closing dehydrogenation of o-arylene isocyanides. These reported disadvantages include the difficulty of preparing reaction initiators, the long reaction time, and the need for metal catalysis. In this paper, we developed a kind of reaction substrate with quinoline N-oxide and alcohol (phenol). A new method for the rapid and efficient synthesis of 2-alkoxy quinoline derivatives by hydrocarbon activation with ordinary H- phosphite. The advantages of this method are as follows: rapid and efficient, mild conditions, no metal, and no metal. The atomic economy is good and the substrate is widely used. In the aspect of mechanism research, the experimental mechanism is deeply discussed by means of nuclear magnetic phosphorus spectrum tracking method. The main research contents of this thesis are as follows: 1. The research progress and application of quinoline compounds are summarized. 2. N-propanol and quinoline N-oxide are used as template reaction of H- phosphorous acid. Types and amounts of esters, The amount of reactants, kinds and amounts of alkali, solvent, carbon tetrachloride, reaction time, reaction temperature and so on were optimized. The optimum reaction conditions were obtained by using 0.5 mL carbon tetrachloride of 0. 8 mmol n-propanol, 0. 8 mmol diisopropyl phosphite and 2 equiv diisopropyl ethylamine, and placed in 3 m L acetonitrile solvent. Under the optimum reaction conditions, the suitability of substrate for template reaction was investigated. This method is widely used in alcohol, phenol, quinoline N-oxide with different substituents and isoquinoline N-oxide. A total of 26 target products were synthesized, the structures of which were confirmed by 1H NMR-13C NMRHR MS et al. 4. The mechanism of the experiment was described in combination with the 31P NMR tracking experiment.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：O626

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