本文選題：喹啉 + 2-氨基喹啉衍生物��； 參考：《鄭州大學(xué)》2016年碩士論文

【摘要】：喹啉及其衍生物廣泛的存在于藥物之中,但是,喹啉類藥物進(jìn)入體內(nèi)之后2-位容易被氧化,大大降低喹啉類藥物的藥效,人們進(jìn)行了大量的研究,試圖在喹啉2-位引入官能團(tuán)以此來保證喹啉類藥物的療效,因此,在喹啉2-位引入胺基制備得到療效更好的2-氨基喹啉類藥物引起了化學(xué)工作者的廣泛關(guān)注。目前報道的合成2-氨基喹啉及其衍生物的方法有:(1)Chichibabin類反應(yīng);(2)2-取代喹啉與胺類的胺基化反應(yīng);(3)傳統(tǒng)的環(huán)加成反應(yīng);(4)金屬催化下喹啉N-氧化物的胺基化反應(yīng)。但是,現(xiàn)有的合成2-氨基喹啉衍生物的方法都存在著明顯的不足:起始反應(yīng)物難以制備,條件苛刻、步驟復(fù)雜、原子經(jīng)濟(jì)性較差。因此,亟需找到一種快速簡便,且條件溫和的方法來制備2-氨基喹啉衍生物。本文結(jié)合本實驗室的研究基礎(chǔ),提出了一種快速、高效合成2-氨基喹啉衍生物的方法,首次利用伯胺類物質(zhì)與喹啉N-氧化物直接合成2-氨基喹啉衍生物,即在H-亞磷酸酯的輔助下,利用脂肪類伯胺和苯胺直接與喹啉N-氧化物發(fā)生親核取代反應(yīng)生成目標(biāo)產(chǎn)物。該方法具有無金屬參與,原子經(jīng)濟(jì)性好,原料易于得到且價格便宜,過程簡單易操作,產(chǎn)率較高,速度較快、適用性較廣等優(yōu)點,和已報道的方法相比優(yōu)勢顯著。本文還對該反應(yīng)的機(jī)理進(jìn)行了預(yù)測,并有效利用了核磁磷譜跟蹤法對該反應(yīng)的機(jī)理進(jìn)行了驗證。本論文主要從以下幾個方面進(jìn)行論述:1.本論文對喹啉及其衍生物的性質(zhì)、合成方法以及實際應(yīng)用等方面進(jìn)行系統(tǒng)的總結(jié)與歸納。2.以喹啉氮氧化物和正丙胺的反應(yīng)為模板反應(yīng),對反應(yīng)物的用量、H-亞磷酸酯種類及其用量、堿的種類及其用量、溶劑、四氯化碳用量、反應(yīng)時間、反應(yīng)溫度等方面進(jìn)行進(jìn)行了系統(tǒng)的優(yōu)化以及篩選,得到了最佳反應(yīng)條件:0.4mmol喹啉N-氧化物與0.4mmol的正丙胺,加入0.8mmol的H-亞磷酸二乙酯,2當(dāng)量的碳酸鉀,0.5m L四氯化碳,置于1毫升的DMF溶劑之中,常溫攪拌反應(yīng)3個小時。3.隨后,在最佳反應(yīng)條件下進(jìn)行了底物的擴(kuò)展,高效合成了24個目標(biāo)產(chǎn)物,均經(jīng)過1H NMR、13C NMR、HR MS等數(shù)據(jù)確認(rèn)。4.利用了核磁磷譜跟蹤法對該反應(yīng)的機(jī)理進(jìn)行了驗證的探究,提出了該反應(yīng)的機(jī)理。
[Abstract]:Quinoline and its derivatives are widely used in drugs. However, after the quinoline drugs enter the body, 2- sites are easily oxidized and greatly reduce the efficacy of quinoline drugs. People have done a lot of research. We tried to introduce functional groups at the quinoline 2- position to ensure the efficacy of quinoline drugs. Therefore, the introduction of amino group in quinoline 2- position was prepared. 2- aminoquinoline drugs with better curative effect have attracted wide attention of chemical workers. The methods for synthesis of 2- aminoquinoline and its derivatives are: (1) Chichibabin reaction; (2) 2- substituted quinoline and amine amines; (3) traditional cycloaddition reaction; (4) metal catalyzed amine oxidation of quinoline N- oxide. There are obvious shortcomings in the existing synthetic methods of 2- amino quinoline derivatives: the initial reactants are difficult to be prepared, the conditions are harsh, the steps are complex, and the atomic economy is poor. Therefore, it is urgent to find a fast, simple and mild method to prepare 2- amino quinoline derivatives. A rapid and efficient synthesis of 2- amino quinoline derivatives is the first time to synthesize 2- amino quinoline derivatives directly from primary amines and quinoline N- oxides. Under the assistance of H- phosphite, the target products are produced by nucleophilic substitution of fatty primary amine and aniline directly with quinoline N- oxide. This method has no metal. Participation, good atomic economy, easy to get and cheap, simple and easy operation process, high yield, fast speed, wide application and so on. Compared with the reported method, the mechanism of the reaction is predicted and the mechanism of the reaction is validated by NMR spectroscopy. The thesis mainly discusses the following aspects: 1. this paper systematically summarizes and summarizes the properties, synthetic methods and practical applications of quinoline and its derivatives and its practical application, and summarizes.2. as a template reaction with the reaction of quinoline nitrogen oxide and positive amines, the amount of reactant, the type and dosage of H- phosphite, the types of alkali and its use. The amount, solvent, the amount of carbon tetrachloride, reaction time and reaction temperature were optimized and screened, and the optimum reaction conditions were obtained: 0.4mmol quinoline N- oxide and 0.4mmol, H-, 2 equivalent potassium carbonate, 0.5m L carbon tetrachloride, in 1 ml DMF solvent, and stirring at normal temperature. After mixing reaction for 3 hours.3., the substrate was expanded at the best reaction condition and 24 target products were synthesized efficiently. All the 24 target products were synthesized through the data confirmed by 1H NMR, NMR, HR MS and so on. The mechanism of the reaction was verified by using NMR spectroscopy to verify the mechanism of the reaction.
【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】：O626.323

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