Study On One-pot Synthesis Of Aminooxoindolin Compounds And Pyrazolylisoindolinone Derivatives

Multicomponent Reactions(MCRs) are synthetic methods in which three or more relatively simple and easily available starting materials are added to the reaction to directly build up complex molecular structure incorporating all joining fragments in a one-pot procedure without the separation of intermediates. MCRs have the advantages of operational simplicity, effective resource utilization and high atomic economy etc. Therefore, MCRs are widely used in design and synthesis of new drugs, combinatorial chemistry and synthesis of natural products. This paper mainly studied the construction two classes of heterocyclic compounds with the characteristics of molecular diversity and complexity, which provides a path for discovery and optimization of lead compounds in the process of drug discovery. This dissertation consists of two parts:The first part is one-pot synthesis of amino-oxoindolin compounds.The amino-oxoindolin and naphthoquinone frameworks widely exist in some natural products and drugs, and they have been hot spots in the research of bioactive organic heterocyclic compounds for the past few years owing to their significant biological and pharmacological activities. Herein, we employed various isatins, 2-hydroxy-1,4-naphthoquinone and ammonium acetate to obtain amino-oxoindolin derivatives successfully with high yield(80%-99%) in ethanol at reflux for the first time.The second part is one-pot synthesis of pyrazolyl-isoindolinone derivatives.Isoindolinone is a vital and common heterocyclic skeleton in natural alkaloids and compounds including isoindolinone motif are found to have a variety of biological activities. Pyrazolone is a kind of heterocyclic system which exists extensively in various natural products and drugs. It has received much attention because of its general application in acaricide, dye, fungicide, herbicide, insecticide and inhibitor. For the first time, we investigated the reaction of different phthalaldehydic acids, pyrazolones and primary amines or ammonium hydroxide through a one-pot procedure to furnish pyrazolyl-isoindolinone derivatives containing the isoindolinone and pyrazolone scaffolds in acetonitrile at reflux. This novel approach has the advantages of short reaction time, environmentally friendliness, easy handling and wide substrate scope giving 32 desired compounds in 50%-96% yield.