银催化邻炔基苯甲醛腙合成多取代异喹啉偶极子

doi:10.11944/j.issn.1000-0518.2017.07.160456

摘要/Abstract

摘要：

将含有不同取代基团的邻炔基苯甲醛腙化合物在乙酸银催化下,以二氯甲烷作溶剂,室温下自身发生环化反应合成N,N-异喹啉偶极子化合物。通过质谱(MS)、核磁共振波谱仪(NMR)等技术手段表征化合物的结构。考察了不同催化剂及其用量、原料配比、溶剂、温度对反应的影响。在最优条件下,反应收率为60%,在底物适应性上最高可达到85%。该方法具有操作简单,反应条件简单温和,产物收率高以及底物适用性好等优点。本文通过对实验条件、底物适用性等方面的探索,解决了以往合成异喹啉偶极子方法学中存在的多步进行、反应温度过高、底物适应性较低等不足与缺点,为制备含此类骨架的化合物提供了新的实验方法。

关键词: 邻炔基苯甲醛腙, 银催化, N, N-异喹啉偶极子衍生物

Abstract:

N,N-Isoquinoline dipole derivatives were synthesized via intramolecular cyclization of o-alkynylbenzaldehyde hydrazones in the presence of silver acetate(AgOAc) in dichloromethane(DCM) at room temperature. The chemical structures of these obtained products were characterized by mass spectrometry and nuclear magnetic resonance spectroscopy(NMR). In addition, the effect of catalysts and their loadings, raw material ratios, solvents and temperatures on the yields was investigated. The target compound (3-(((methoxycarbonyl)oxy)methyl)isoquinolin-2-iu-m-2-yl)(tosyl)-amide is obtained in 60% yield and the substrate adaptability can be up to 85% under optimum conditions. This method has advantages of easy operation, mild reaction condition and functional group tolerance. Through the exploration of experimental conditions and substrate applicability, this paper solves the disadvantages and shortcomings of the method of synthesizing isoquinoline dipole compounds in the past, which provides a new experimental method for the preparation of compounds containing such skeletons.

Key words: o-alkynylbenzaldehyde hydrazone, silver-catalyzed, N, N-isoquinoline dipole

石赟, 李孟生, 魏晓琳. 银催化邻炔基苯甲醛腙合成多取代异喹啉偶极子[J]. 应用化学, 2017, 34(7): 795-800.

SHI Yun, LI Mengsheng, WEI Xiaolin. Synthesis of N,N-Isoquinoline Dipoles via Intramolecular Cyclization of o-Alkynylbenzaldehyde Hydrazones[J]. Chinese Journal of Applied Chemistry, 2017, 34(7): 795-800.

参考文献

[1]	Nammalwar B and Bunce R A. Recent Syntheses of 1,2,3,4-Tetrahydroquinolines,2,3-dihydro-4(1H)-quinolin-ones and 4(1H)-quinolinones Using Domino Reactions[J]. Molecules,2014,19(1):204-232.
[2]	Verhoest P R,Chapin D S,Corman M,et al.Discovery of a Novel Class of Phosphodiesterase 10A Inhibitors and Identification of Clinical Candidate 2-[4-(1-Methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline(PF-2545920) for the Treatment of Schizophrenia[J]. J Med Chem,2009,52(16):5188-5196.
[3]	Mouscadet J F, Desma le D. Chemistry and Structure-activity Relationship of the Styrylquinoline-Type HIV Integrase Inhibitors[J]. Molecules,2010,15(5):3048-3078.
[4]	Chen Z,Wu J. Efficient Generation of Biologically Active H-Pyrazolo[5,1-a]isoquinolines via Multicomponent Reaction[J]. Org Lett,2010,12(21):4856-4859.
[5]	Ding Q P,Chen Z Y,Wu J,et al.Highly Efficient Electrophilic Cyclization of N'-(2-Alkynylbenzylidene) Hydrazides[J]. Tetrahedron Lett,2009,50(3):340-342.
[6]	Ye S Q,Gao K,Wu J. Three-component Reactions of 2-Alkynylbenzaldoxime, α,β-Unsaturated Carbonyl Compound with Bromine or Iodine Monochloride[J]. Adv Synth Catal,2010,352:1746-1751.
[7]	Chen Z,Ding Q P,Wu J,et al.Silver Triflate-catalyzed or Electrophile-mediated Tandem Reaction of N'-(2-Alkynylbenzylidene)hydrazide with Dimethyl Acetylene Dicarboxylate[J]. Adv Synth Catal,2009,351:1692-1698.
[8]	Ding Q P,Wang D,Peng Y,et al.One-Pot Two-Step Synthesis of 1-Position Arylated 1,3-Disubstituted Isoquinoline N-Oxides[J]. Tetrahedron,2012,68:8869.
[9]	Gillie A D,Reddy R J,Davies P W. Efficient and Flexible Synthesis of Highly Functionalised 4-Aminooxazoles by a Gold-catalysed Intermolecular Formal [3+2] Dipolar Cycloaddition[J]. Adv Synth Catal,2016,358(2):226-239.
[10]	Zhang H,Wang Z Q,Katritzky A R. Synthesis of Pyridinium N-Aryl/N-Heteroarylcyclic Ylides as Potential Energetic Materials[J]. Tetrahedron Lett,2016,57(1):20-24.
[11]	Madu C E,Lovely C J. A Pauson-Khand Approach to the Hamigerans[J]. Org Lett,2007,9(23):4697-4700.
[12]	Ye F,Hossain M L,Xu Y,et al.Synthesis of Allyl Allenes Through Three-component Cross-coupling Reaction of N-Tosylhydrazones, Terminal Alkynes, and Allyl Halides[J]. Chem Asian J,2013,44(46):1404-1407.
[13]	Peshkov V A,Pereshivko O P,Ermolat'ev D S. Synthesis of Isoquinolinium-2-yl Amides via Ag(Ⅰ)-catalyzed Ring Closure of N'-(2-Alkynylbenzylidene)hydrazides[J]. Synthesis,2011,(20):3371-3374.
[14]	Liu Y C,Zhen W C,Li X W,et al.Silver(I)-catalyzed Addition-Cyclization of Alkyne-functionalized Azomethines[J]. Org Lett,2013,15(4):874-877.