本文選題：C-H官能化　切入點：雜環(huán)化合物　出處：《江南大學(xué)》2017年碩士論文

【摘要】：作為當(dāng)代有機(jī)合成的重要手段之一,C-H官能化反應(yīng)無需對底物進(jìn)行預(yù)官能化,降低了鹵化物以及無機(jī)鹽等廢棄物的排放,簡化了反應(yīng)步驟,且具有較高的原子經(jīng)濟(jì)性。因此,對于可持續(xù)發(fā)展綠色化學(xué)來說,研究C-H官能化反應(yīng)具有非常重要的意義。氧化吲哚和異喹啉酮骨架廣泛存在于天然產(chǎn)物、生物堿和藥物活性分子中,關(guān)于該類化合物的合成方法大都存在反應(yīng)條件苛刻、使用昂貴或毒性較大的試劑、反應(yīng)底物適用范圍窄和操作復(fù)雜等問題,因此,利用C-H官能化反應(yīng)構(gòu)建含氮雜環(huán)化合物具有重要的研究價值。本論文重點研究了基于丙烯酰胺衍生物參與的C-H官能化反應(yīng),構(gòu)建氧化吲哚類和異喹啉酮類的含氮雜環(huán)化合物,具體研究內(nèi)容如下:1.在布朗斯特酸催化下,N-芳基丙烯酰胺與酮發(fā)生串聯(lián)自由基加成/環(huán)化反應(yīng),生成相應(yīng)的氧化吲哚衍生物。另外,在相同的酸催化條件下使用N-芳基磺酰基丙烯酰胺作為底物可以制備γ-過氧化酮衍生物。2.在催化劑甲烷磺酸和氧化劑TBHP存在條件下,丙烯酰胺衍生物與酮或醇發(fā)生自由基加成/環(huán)化反應(yīng),提供了一種有效的途徑合成4-取代-1,3-異喹啉二酮衍生物。此外,丙烯酰胺與醇生成的產(chǎn)物還可以轉(zhuǎn)化為四氫呋喃并異喹啉酮衍生物。3.在催化劑Cu(OAc)_2和配體1,10-phen存在條件下,丙烯酰胺衍生物與NFSI發(fā)生自由基加成/環(huán)化反應(yīng),報道了一種合成磺酰胺取代的1,3-異喹啉二酮衍生物的新方法。4.在催化劑Pd(OAc)_2和配體DPE-phos存在條件下,丙烯酰胺衍生物與BrCF_2CO_2Et發(fā)生自由基串聯(lián)的二氟烷基化/環(huán)化反應(yīng),發(fā)展了一種合成含有酯基的1,3-異喹啉二酮衍生物的新方法。其中,該反應(yīng)的產(chǎn)物可以通過NaBH_4還原得到含有羥基的1,3-異喹啉二酮衍生物,并且氟代試劑可以擴(kuò)展到全氟代烷基碘化物和溴二氟甲基膦酸酯。5.在催化劑AgNO_3或Ru(bpy)_3Cl_2·6H_2O存在條件下,丙烯酰胺衍生物與硫化物或磺酰氯發(fā)生自由基加成/環(huán)化反應(yīng),發(fā)展了一種合成含砜基的1,3-異喹啉二酮衍生物的新方法。以上研究的內(nèi)容主要使用了以下的研究方法:1.分別以各部分的反應(yīng)底物為原料,對反應(yīng)的影響因素進(jìn)行篩選,最終得到最佳反應(yīng)條件,并探究了反應(yīng)底物的適用性。其中,篩選的影響因素包括催化劑的種類及用量、添加劑的種類及用量、反應(yīng)溫度、反應(yīng)時間、反應(yīng)氣氛、反應(yīng)溶劑的種類和原料的摩爾比等。2.利用核磁共振儀、質(zhì)譜儀、紅外光譜儀、熔點儀等儀器對目標(biāo)產(chǎn)物進(jìn)行鑒定和表征,確認(rèn)目標(biāo)產(chǎn)物的結(jié)構(gòu)。3.通過設(shè)計控制實驗、自由基捕獲實驗和動力學(xué)實驗等,對反應(yīng)進(jìn)程進(jìn)行跟蹤檢測,從而推測出可能的反應(yīng)機(jī)理。
[Abstract]:As one of the most important methods of organic synthesis, C-H functionalization does not need to prefunctionalize the substrate, reduce the discharge of wastes such as halides and inorganic salts, simplify the reaction steps, and have high atomic economy. For the sustainable development of green chemistry, the study of C-H functionalization is of great significance. Indoles and isoquinolones are widely present in natural products, alkaloids and drug active molecules. There are many problems in the synthesis of these compounds, such as harsh reaction conditions, expensive or toxic reagents, narrow range of application and complex operation of the reaction substrates, and so on. It is of great value to construct nitrogen-containing heterocyclic compounds by C-H functionalization reaction. In this paper, the C-H functionalization reaction based on acrylamide derivatives was studied to construct nitrogen-containing heterocyclic compounds of indoles and isoquinolones. The specific contents of the study are as follows: 1. In the presence of Brownstearic acid, N-aryl acrylamide and ketone undergo series radical addition / cyclization to form corresponding oxindole-derived derivatives. In the presence of methanesulfonic acid and oxidant TBHP, 緯 -ketone derivatives can be prepared by using N-aryl sulfonyl acrylamide as substrate under the same acid catalytic conditions. The free radical addition / cyclization of acrylamide derivatives with ketones or alcohols provides an effective way to synthesize 4- substituted-1-3-isoquinolinedione derivatives. The product of acrylamide and alcohol can also be transformed into tetrahydrofuran isoquinolinone derivatives. In the presence of catalyst Cu(OAc)_2 and ligands 1 ~ (10 ~ (-phen)), acrylamide derivatives react with NFSI by radical addition / cyclization. A new method for the synthesis of sulfonamide-substituted 1 / 3-isoquinolinedione derivatives was reported. In the presence of catalyst Pd(OAc)_2 and ligands DPE-phos, acrylamide derivatives reacted with BrCF_2CO_2Et in series of difluoroalkylation / cyclization. A new method for the synthesis of 1,4-isoquinolinedione derivatives containing ester groups has been developed, in which the products of the reaction can be reduced by NaBH_4 to obtain 1H 3-isoquinolinone derivatives containing hydroxyl groups. And fluorinated reagents can be extended to perfluoroalkyl iodides and bromodifluoromethyl phosphonates. In the presence of catalyst AgNO_3 or Ru(bpy)_3Cl_2 6H_2O, acrylamide derivatives react with sulfides or sulfonyl chloride by free radical addition / cyclization. A new method for the synthesis of sulfo-containing 1 / 3-isoquinolinedione derivatives was developed. The following research methods were used in the above studies: 1. The factors affecting the reaction were screened using each part of the reaction substrate as the raw material, respectively. Finally, the optimum reaction conditions were obtained, and the applicability of the reaction substrate was explored. Among them, the factors affecting the selection included the type and amount of catalyst, the type and amount of additives, the reaction temperature, the reaction time, the reaction atmosphere, The kind of solvent and the molar ratio of raw material etc. 2. The target product was identified and characterized by NMR, mass spectrometer, infrared spectrometer, melting point instrument, etc. The structure of the target product was confirmed by designing and controlling experiment. The free radical trapping experiment and kinetic experiment were used to track and detect the reaction process, and the possible reaction mechanism was deduced.
【學(xué)位授予單位】：江南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：O621.25

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