發(fā)布時(shí)間：2019-02-21 08:35

【摘要】：乙烯砜類(α,β-不飽和砜)是重要的有機(jī)分子,它們是很多藥物中的重要結(jié)構(gòu)片段,如半胱氨酸蛋白酶(cysteine proteases)抑制劑,膜蛋白轉(zhuǎn)肽酶(SrtA(sortase A))抑制劑等。而且,在有機(jī)化學(xué)中,它們廣泛用作Michael受體。由于它們的合成用途和潛在的生物活性,近些年,芳基乙烯砜類化合物的合成研究吸引了大批有機(jī)化學(xué)家的關(guān)注。已報(bào)道的合成芳基乙烯砜類涉及到約十余種不同反應(yīng)方法,結(jié)合已報(bào)道的相關(guān)方法,我們提出了本課題,以肉桂酸與苯亞磺酸鈉為原料合成芳基乙烯砜類,進(jìn)行了如下的實(shí)驗(yàn)探究：第一、簡(jiǎn)要介紹了偶聯(lián)反應(yīng)的發(fā)展歷程和綜述了一些已經(jīng)報(bào)道的有關(guān)偶聯(lián)反應(yīng)合成芳基乙烯砜類的研究方法；第二、通過對(duì)催化劑的種類、溶劑、反應(yīng)溫度、反應(yīng)環(huán)境等的篩選,進(jìn)行了一系列的實(shí)驗(yàn)探究,得到了反應(yīng)的最優(yōu)條件：5 mol% Mn(OAc)2,1.0 equiv肉桂酸,3.0 equiv苯亞磺酸鈉,2.0 mL DMSO,空氣條件下,110℃下反應(yīng)12h,在此反應(yīng)條件下得到產(chǎn)物芳基不飽和砜,產(chǎn)率達(dá)到86%。第三、在獲得了最優(yōu)反應(yīng)條件之后,我們探索了本脫羧反應(yīng)的底物范圍。發(fā)現(xiàn)以不同的肉桂酸參與反應(yīng)時(shí),產(chǎn)率范圍從57%-80%。底物含吸電子基或供電子基如甲基、甲氧基、氟、氯、溴、硝基等時(shí),得到了預(yù)期的產(chǎn)物和滿意的產(chǎn)率。鄰、間、對(duì)位取代的的硝基肉桂酸產(chǎn)率變化不大。苯亞磺酸鈉進(jìn)行底物擴(kuò)展,反應(yīng)產(chǎn)率范圍53%-76%。而對(duì)于烷基磺酸鈉甲基磺酸鈉參加反應(yīng),實(shí)驗(yàn)結(jié)果發(fā)現(xiàn)沒能得到預(yù)期的產(chǎn)物。根據(jù)反應(yīng)過程中產(chǎn)生的一些現(xiàn)象,給出了一些合理的分析解釋。最后,根據(jù)實(shí)驗(yàn)的結(jié)果和已報(bào)道的相關(guān)文獻(xiàn)分析提出可能的反應(yīng)機(jī)理并對(duì)其進(jìn)行了簡(jiǎn)要的解釋。
[Abstract]:Ethylene sulfone (偽, 尾 -unsaturated sulfone) is an important organic molecule, which is an important structural fragment in many drugs, such as cysteine protease (cysteine proteases) inhibitor, membrane protein transpeptidase (SrtA (sortase A) inhibitor and so on. Moreover, they are widely used as Michael receptors in organic chemistry. Due to their synthetic uses and potential biological activities, the synthesis of aryl ethylene sulfone has attracted the attention of a large number of organic chemists in recent years. The synthesis of aryl ethylene sulfone has been reported, which involves about ten different reaction methods. In combination with the reported methods, we have put forward the subject of synthesizing aryl ethylene sulfone from cinnamic acid and sodium benzenesulfonate as raw materials, and the synthesis of aryl ethylene sulfone from cinnamic acid and sodium benzenesulfonate has been studied. The following experiments were carried out: first, the development of coupling reactions and some reported research methods on the synthesis of aryl ethylene sulfone were briefly introduced. Secondly, through the screening of catalyst, solvent, reaction temperature, reaction environment and so on, a series of experiments were carried out. The optimum reaction conditions were obtained as follows: 5 mol% Mn (OAc) 21.0 equiv cinnamic acid, 3. 0 equiv sodium benzenesulfonic acid, 2. 0 mL DMSO, air, 12 h reaction at 110 鈩，

本文編號(hào)：2427390