一种合成N-芳基-3,4-二取代异喹啉酮类化合物的方法
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摘要
N-芳基-3,4-二取代异喹啉酮类化合物是一类具有广泛生物活性和独特药理活性的杂环化合物,对该类化合物的合成研究一直是有机化学和药物化学领域的研究热点。以邻炔苯甲酰胺化合物为反应底物,在NaH作用下,以碳负离子作为亲核基团进攻炔基进行关环反应得到异喹啉酮类化合物,产物结构经核磁共振和质谱分析确证。该方法原料易得、反应条件温和、收率中等、易于引入各种取代基团,为异喹啉酮类化合物的结构修饰和衍生化发展提供了一种十分有效的方法。
N-aryl-3,4-disubstituted isoquinolinone are important heterocyclic compounds with a wide spectrum of biological activities and unique pharmacological activity. The synthesis of these compounds has been a research hotspot in organic chemistry and medicinal chemistry. In this study, based on the reaction of o-alkynylbenzamide with NaH, the isoquinoline compounds were obtained by cyclization reaction that used carbon negative ions as nucleophilic groups to attack alkynes. NMR and MS analysis have been performed to confirm the products. The synthetic method reported here has many advantages such as facilely accessible starting materials, mild reaction conditions, moderate yield and convenience to introduce various substituent groups, providing a highly effective way for structural modification and derivatization of isoquinoline compounds.
N-aryl-3,4-disubstituted isoquinolinone are important heterocyclic compounds with a wide spectrum of biological activities and unique pharmacological activity. The synthesis of these compounds has been a research hotspot in organic chemistry and medicinal chemistry. In this study, based on the reaction of o-alkynylbenzamide with NaH, the isoquinoline compounds were obtained by cyclization reaction that used carbon negative ions as nucleophilic groups to attack alkynes. NMR and MS analysis have been performed to confirm the products. The synthetic method reported here has many advantages such as facilely accessible starting materials, mild reaction conditions, moderate yield and convenience to introduce various substituent groups, providing a highly effective way for structural modification and derivatization of isoquinoline compounds.
引文
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[4] BESANCON M,SIMON A,SACHS G,et al.Sites of reaction of the gastric H,K-ATPase with extracytoplasmic thiol reagents[J].Journal of biological chemistry,1997,272(36):22438-22446.
[5] LANE J W,ESTEVEZ A,MORTARA K,et al.Antitumor activity of tetrahydroisoquinoline analogues 3-epi-jorumycin and 3-epi-renieramycin G[J].Bioorganic & medicinal chemistry letters,2006,16(12):3180-3183.
[6] NI Y,KRCHNAK V,LEBL M.New approach for preparation of 2,3,7-trisubstituted 3,4-dihydroisoquinolinone libraries on solid phase[J].Molecular diversity,2000,5(3):153-161.
[7] ROBISON M M,ROBISON B L.The rearrangement of isoquinoline-N-oxides[J].Journal of organic chemistry,1956,21(12):1337-1341.
[8] SHOWALTER H D H,SERCEL A D,STIER M A,et al.Synthesis of 3,4-dihydro-1(2H)-isoquinolinonesxs[J].Journal of heterocyclic chemistry,2001,38(4):961-964.
[9] LEE A W M,CHAN W H,CHAN E T T.A facile total synthesis of isoquinolone alkaloids[J].Journal of the chemical society perkin transactions,1992,23(3):309-310.
[10] VARELA J A,SAá C.Construction of pyridine rings by metal-mediated [2+2+2]cycloaddition[J].Chemical reviews,2003,103(9):3787-3802.
[11] AND I N,YAMAMOTO Y.Transition-metal-catalyzed reactions in heterocyclic synthesis[J].Chemical reviews,2004,35(31):2127-3298.
[12] ALONSO F,BELETSKAYA I P,YUS M.Transition-metal-catalyzed addition of heteroatom-hydrogen bonds to alkynes[J].Chemical reviews,2004,35(36):3079-3159.
[13] 贾义霞,李英龙,刘人荣.钯催化吲哚的去芳香化双芳基化[J].浙江工业大学学报,2017,45(4):387-390.
[14] 施介华,王炯杰.CuCl2/Al2O3催化氮杂环的N-芳基化反应[J].浙江工业大学学报,2013,41(2):126-132.
[15] PATIL N T,YAMAMOTO Y.Coinage metal-assisted synthesis of heterocycles[J].Chemical reviews,2008,108(8):3395-3442.
[16] ALVAREZ-CORRAL M,MU?OZ-DORADO M,RODRíGUEZ-GARCíA I.Silver-mediated synthesis of heterocycles[J].Chemical reviews,2008,108(8):3174-3198.
[17] 陈万里,伍松玲.DBU骨架含N杂环的合成及产物的核磁共振分析[J].浙江工业大学学报,2018,46(1):90-94.
[18] CHEN W L,CUI J,ZHU Y H,et al.DBU-promoted cyclization of ortho-(3-hydroxy-1-alkynyl)benzamide:synthesis of trans-3,4-dihydroisoquinolin-1(2H)-ones and (E)-4-(1-alkenyl)isoquinolin-1(2H)-ones[J].Journal of organic chemistry,2012,43(21):1585-1591.