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An Efficient One-Pot Multicomponent Synthesis of 4-Aza-Podophyllotoxin Derivatives in Ionic Liquid

DOI: 10.1155/2013/169695

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Abstract:

A simple, green, and efficient procedure for the synthesis of 4-aza-podophyllotoxin derivatives by using a one-pot three-component reaction of benzaldehydes, 1,3-cyclohexanediones, and anilinolactones in the presence of catalytic amount of alum in 1-butyl-3-methylimidazolium triflate as green media is described. This reaction proceeded under mild conditions with the use of an inexpensive and readily available catalyst, high to excellent yields, and simple workup procedure. 1. Introduction Multicomponent reactions (MCRs) are one-pot processes in which three or more reactants come together in a single reaction vessel to give a final product containing substantial elements of all the reactants [1–4], and in recent year much attention has been directed toward the one-pot multicomponent reactions, because of their wide range of applications in pharmaceutical chemistry for the production of structural scaffolds and combinatorial libraries for drug discovery [5–8]. The strategies of MCRs offer significant advantages over conventional linear-type syntheses because of high degree of atom economy, high selectivity, and procedural simplicity due to formation of carbon-carbon and carbon-heteroatom bonds in one-pot procedure [9–11]. MCRs, particularly those performed in green and eco-friendly media, have become increasingly useful tools for the synthesis of chemically and biologically important compounds because of their environmentally friendly atom economy and green characteristics, and the “greening” of global chemical processes has became a major issue in the chemical industry [12, 13]. Organic reactions in ionic liquid (IL) media have received the considerable attention of synthetic organic chemists in recent years; IL is an environmentally friendly solvent with unique properties such as high ionic conductivity, nonvolatility, high thermal stability, nonflammability, and miscibility with organic compounds, especially with the heterocyclic compounds [14–17]. Because of these useful properties numerous works have been published in the last decades reporting the possibility to perform several organic reactions and catalyzed processes in these green media [18–20]. 1,4-Dihydropyridine compounds are molecules based upon pyridine and this nucleus is one of the significant core structures among the most extensively natural and unnatural heterocyclic compounds, have been recognized as vital drugs for the treatment of cardiovascular diseases, and are well known as calcium channel modulators [21, 22]. 1,4-Dihydropyridine derivatives exhibit a variety of biological

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