【摘要】：喹啉衍類化合物是一類重要的雜環(huán)化合物,其廣泛存在于自然界中,展現(xiàn)出了諸多的生物活性和藥理活性,如抗瘧、抗腫瘤、抗炎、抗菌活性等。因此,如何高效地構(gòu)筑喹啉分子一直是有機(jī)合成領(lǐng)域的重要研究課題。自十九世紀(jì)以來,科學(xué)家們開發(fā)了多種經(jīng)典的喹啉類化合物的合成方法,如Skraup、Doebner-von Miller、Friedlander、Pfitzinger、Conrad-Limpach反應(yīng)等。雖然這些方法都具有很好的應(yīng)用價(jià)值,但它們?nèi)源嬖谥T多局限性,如反應(yīng)條件苛刻,較長(zhǎng)的反應(yīng)時(shí)間,反應(yīng)過程會(huì)產(chǎn)生大量的副產(chǎn)物,對(duì)環(huán)境污染的同時(shí)又對(duì)產(chǎn)物的分離造成困難。近些年來,過渡金屬催化的串聯(lián)已經(jīng)成為構(gòu)筑結(jié)構(gòu)復(fù)雜分子的高效、簡(jiǎn)潔策略,在反應(yīng)過程中,多個(gè)化學(xué)鍵的斷裂和形成僅通過一“鍋”完成。因此,開發(fā)過渡金屬催化的串聯(lián)反應(yīng)用以合成喹啉類衍生物具有重要的研究意義。本文研究了銅催化炔基亞胺和重氮化合物的串聯(lián)反應(yīng),在溫和的條件下,簡(jiǎn)潔、高效地合成了一系列結(jié)構(gòu)新穎的喹啉類衍生物。該反應(yīng)過程涉及聯(lián)烯中間體的形成,6-π電環(huán)化,1,3氫遷移。我們考察了不同催化劑、反應(yīng)溫度、溶劑、投料比等反應(yīng)條件,得到了最佳的反應(yīng)條件,即在60℃條件下,以碘化亞銅為催化劑,N,N-二甲基甲酰胺為溶劑的合成條件。并詳細(xì)探索了底物的適用范圍,提出了反應(yīng)機(jī)理。
[Abstract]:Quinoline derivatives are an important class of heterocyclic compounds, which widely exist in nature and exhibit many biological and pharmacological activities, such as antimalarial, anti-tumor, anti-inflammatory and antibacterial activities. Therefore, how to efficiently construct quinoline molecules has been an important research topic in the field of organic synthesis. Since the nineteenth century, scientists have developed a variety of classical synthesis methods of quinoline compounds, such as Skraup,Doebner-von Miller,Friedlander,Pfitzinger,Conrad-Limpach reaction. Although these methods have good application value, but they still have many limitations, such as harsh reaction conditions, longer reaction time, reaction process will produce a large number of by-products, At the same time, it is difficult to separate the products from the environment. In recent years, the series of transition metal catalysis has become an efficient and simple strategy to construct complex molecules. In the process of reaction, the breakage and formation of multiple chemical bonds are accomplished only by a "pot". Therefore, the development of transition metal catalyzed series reaction for the synthesis of quinoline derivatives has important significance. A series of novel quinoline derivatives were synthesized succinctly and efficiently under mild conditions by copper-catalyzed series reaction of alkynyl imines with diazo compounds. The reaction involves the formation of diene intermediates, the electrocyclization of 6- 蟺, and the migration of 1 / 3 hydrogen. The optimum reaction conditions were obtained under different reaction conditions, such as reaction temperature, solvent and feed ratio. The optimum reaction conditions were obtained at 60 鈩，

本文編號(hào)：2351991