發(fā)布時間：2018-06-19 11:00

  本文選題：喹啉氮氧 + H-亞磷酸酯�。� 參考：《鄭州大學》2017年碩士論文

【摘要】：喹啉及其衍生物是一類非常重要的有機化合物,具有抗菌、消炎、抗高血壓、抗過敏、抗抑郁、抗腫瘤、抗癌及抗HIV等多種生物及藥物活性,在有機化學、天然產(chǎn)物及藥物化學等領(lǐng)域具有非常重要的應(yīng)用。然而,喹啉類化合物很容易在人體內(nèi)被氧化形成2-羥基衍生物,從而大大降低甚至失去了它的藥物活性及生物活性,因此常常通過對喹啉的2位進行修飾,從而阻止這樣一個氧化過程的發(fā)生。以往人們主要通過在喹啉的2位構(gòu)建碳雜鍵的方式對其進行修飾,而通過在2位構(gòu)建C-C鍵修飾喹啉的方法數(shù)量有限,且主要集中于喹啉2位芳基化的改造,而喹啉2位烷基化烷烴化的改造方法卻十分有限。本文提出了一種利用原子經(jīng)濟性極高的交叉脫氫偶聯(lián)反應(yīng)實現(xiàn)喹啉2位烷基化的方案,具有綠色、廉價、實用等優(yōu)勢。即:使用一鍋煮的方法在常溫常壓敞口條件下,將喹啉氮氧化物、活潑亞甲基試劑、H-亞磷酸二乙酯以及四氯化碳和碳酸鉀置于DMF溶液中,攪拌三小時,萃取分離即可得到目標化合物。該方法具有原料廉價易得、反應(yīng)快速、條件溫和、區(qū)域選擇性高等優(yōu)點,為制備2-烷基喹啉衍生物提供了一種方便的途徑。β-羥基砜類化合物是一種常見的有機合成中間體,廣泛應(yīng)用于生物活性分子的不對稱合成中。除此之外,β-羥基砜類化合物還具有抗癌、抗真菌等藥物活性。傳統(tǒng)合成β-羥基砜類化合物的方法主要有:(i)亞磺酸鈉鹽與環(huán)氧衍生物的親核反應(yīng)。(ii)β-羰基砜的還原反應(yīng)(iii)α,β-不飽和砜的羥基化反應(yīng)。(vi)烯烴與亞磺酸(鹽)、磺酰衍生物的加成氧化反應(yīng)等。本文首次利以叔丁基亞磺酰胺為砜源和苯乙烯類化合物在40 o C條件下反應(yīng),一鍋煮一步合成β-羥基砜類化合物,為β-羥基砜類化合物的合成提供了一種新思路。與以往方法相比,本方法具有反應(yīng)物便宜易得,反應(yīng)條件溫和步驟簡單的優(yōu)勢。本論文的主要研究內(nèi)容如下:(一)喹啉2位烷基化新方法研究:1.對喹啉及其衍生物的性質(zhì)、合成方法及實際應(yīng)用進行了總結(jié)。2.以喹啉氮氧和乙酰乙酸乙酯為底物,對反應(yīng)時間、反應(yīng)溫度、原料的比例、磷試劑的種類和用量、堿的種類和用量、四氯化碳的用量、溶劑的種類及用量進行了篩選。優(yōu)化的條件為:喹啉氮氧0.4 mmol,乙酰乙酸乙酯0.4 mmol,H-亞磷酸二乙酯0.8 mmol,碳酸鉀0.8 mmol,四氯化碳0.5 m L及1.0 m L的DMF,在40 o C條件下反應(yīng)3 h。3.在優(yōu)化的反應(yīng)條件下,以含有不同取代基的喹啉化合物和含有不同吸電子基的活潑亞甲基化合物為底物,考察了反應(yīng)的適用范圍。共合成23個目標化合物,其結(jié)構(gòu)均通過了~1H,~(13)C NMR和HR MS的表征。4.通過自由基阻斷等手段對反應(yīng)的機理進行了深入探究。(二)β-羥基砜合成新方法研究:1.以苯乙烯類化合物和叔丁基亞磺酰胺為底物,對反應(yīng)的時間、溫度、底物比例、催化劑、磷試劑、酸以及溶劑的種類和用量進行了篩選優(yōu)化。結(jié)果為:苯乙烯0.5 mmol,叔丁基亞磺酰胺0.5 mmol,五水硫酸銅20 mmol%,亞磷酸0.75 mmol,三氟乙酸1.0 mmol,無溶劑40 o C條件下攪拌反應(yīng)12 h。2.在最優(yōu)條件下,考察了反應(yīng)對不同苯乙烯類化合物的適用性,合成了一系列β-羥基砜類化合物,目標產(chǎn)物均經(jīng)過~1H,~(13)C NMR和HR MS的表征。3.對反應(yīng)機理進行了探究。
[Abstract]:Quinoline and its derivatives are very important organic compounds. They have many biological and drug activities, such as antibacterial, anti-inflammatory, anti hypertension, antiallergic, antidepressant, antitumor, anticancer and anti HIV, and have very important applications in organic chemistry, natural products and drug chemistry. However, quinoline compounds are very easy to be in human body. The oxidation of 2- hydroxyl derivatives, thus greatly reducing or even losing its drug activity and biological activity, often modifies the 2 sites of quinoline to prevent such an oxidation process. In the past, it was mainly modified by 2 bits of quinoline to construct carbon heterozygous bonds, and by the construction of 2 bits of C-C. The method of modifying quinoline by key is limited and mainly concentrates on the transformation of quinoline 2 bit arylation, while the modification methods of alkylation of quinoline 2 bit alkylalkylation are very limited. In this paper, a scheme to realize 2 bit alkylation of quinoline by cross dehydrogenation coupling reaction with high atomic economy has been proposed, which has the advantages of green, cheap and practical. In one pot, the target compound can be obtained by mixing quinoline nitrogen oxide, active methylene reagent, two ethyl H- phosphite, carbon tetrachloride and potassium carbonate in DMF solution at normal temperature and atmospheric pressure. The target compound can be obtained by extraction and separation for three hours. The method has the advantages of easy to obtain low price, rapid reaction, mild conditions and high regional selectivity. It provides a convenient way for the preparation of 2- alkyl quinoline derivatives. The beta hydroxyl sulfone is a common organic synthesis intermediate and is widely used in the asymmetric synthesis of bioactive molecules. In addition, the beta hydroxy sulfone compounds also have antitumor and antifungal activity. The traditional synthesis of beta hydroxyl sulfone is a kind of traditional synthesis of beta hydroxyl sulfone. The main methods are: (I) nucleophilic reaction of sodium sulfonic acid sodium salt and epoxy derivatives. (II) reduction reaction of beta carbonyl sulfone (III) alpha, hydroxylation of beta unsaturated sulfone. (VI) olefin and sulfonic acid (salt), sulfonyl derivative oxidation reaction, etc. This article first used tert butyl sulfonamide as sulfone source and styrene compound in 40 The synthesis of beta hydroxy sulfone compounds in one pot one pot under the condition of O C, provides a new idea for the synthesis of beta hydroxyl sulfone compounds. Compared with the previous methods, this method has the advantages of cheap and easy reactant and simple reaction conditions. The main contents of this paper are as follows: (I) new methods of quinoline 2 bit alkylation 1. the properties, synthesis methods and practical applications of quinoline and its derivatives were summarized. The reaction time, reaction temperature, proportion of raw materials, types and dosage of phosphorus reagents, types and dosage of alkali, the amount of carbon tetrachloride, the type and dosage of solvent were selected and optimized by.2., which was used as the substrate of quinoline nitrogen and oxygen and ethyl acetoacetate as substrates. Conditions are: quinoline nitrogen oxygen 0.4 mmol, ethyl acetoacetate 0.4 mmol, H- phosphoric acid two ethyl 0.8 mmol, potassium carbonate 0.8 mmol, carbon tetrachloride 0.5 m L and 1 m L DMF, 3 under 40 o C conditions, under the optimized reaction conditions, with different substituents of quinoline compounds and active methylene compounds containing different absorbing electronic groups. The application scope of the reaction was investigated. A total of 23 target compounds were synthesized and their structures were investigated through ~1H, ~ (13) C NMR and HR MS by.4. through free radical blockage. (two) a new method for the synthesis of beta hydroxyl sulfone: 1. with styrene and tert butyl sulfonamide as the substrate. The optimum time, temperature, substrate ratio, catalyst, reagent, acid and solvent were selected and optimized. The results were as follows: styrene 0.5 mmol, tert butyl sulfonamide 0.5 mmol, five water copper sulfate 20 mmol%, phosphoric acid 0.75 mmol, three FLUOROACETIC acid 1 mmol, and solvent 40 o C under the optimum conditions of 12 h.2. under optimum conditions A series of beta hydroxyl sulfone compounds were synthesized by the reaction to different styrene compounds. The target products were all investigated by ~1H, ~ (13) C NMR and HR MS, and the reaction mechanism was investigated.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R914

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