Studies On Acid-promoted Rapid Solvent-free Access To Multisubstituted 1,4-dihydropyridines

β-Ketothioamides, β-oxodithioesters, and β-enaminonitriles acting as reaction intermediates, have many reactive centers. They are versatile building blocks for the rapid construction of various heterocyclic compounds.In the first chapter, the structure, reaction types and extensive applications of three highly reactive intermediates(β-ketothioamides, β-oxodithioesters, β-enaminonitriles and multisubstituted 1,4-dihydropyridines) in organic synthesis was summarized respectively.1,4-Dihydropyridines are an important class of N-heterocyclic scaffold in medicine, aquaculture and organic syntheses field. In chapter two, a facile and efficient method for the regioselective synthesis of 1,4-dihydropyridines derivatives has been developed by solvent-free three-component reactions of β-ketothioamides, aldehydes, and β-enaminonitriles promoted by AcOH. Herein, the reaction type of the sulfur atom and nucleophilic α-carbon of β-ketothioamides acting as reactive centers has rarely been reported. The optimized conditions for this reaction are AcOH(1.0 equiv) as promoter without any solvent at 90 oC. When the model reaction was conducted under solvent-free conditions, the reaction time was significantly shortened to 5 min. It is noteworthy that all of the products only need washing with dichloromethane(DCM) rather than column chromatography or recrystallization. This easy purification makes this methodology facile, practical, and rapid to execute. And in order to explore the reaction mechanism, many control experiments were conducted.In the third chapter, we developed a general methodology for the synthesis of multisubstituted 1,4-dihydropyridines from β-oxodithioesters, aldehydes and β-enaminonitriles via an three-component one-pot cascade reaction. Optimization of the reaction conditions was carried out including solvent, reaction temperature, stoichiometric amount of starting materials and charging sequence. The optimized conditions for this reaction are AcOH(4.0 equiv) as promoter, CH3 CN as the solvent at 90 oC, and stoichiometric amount of starting materials was 1:1.5:1. It is worth noting that β-enaminonitriles with aldehydes first results in the formation of adducts, then β-oxodithioesters and β-enaminonitriles are all react with adducts, and β-enaminonitriles reacting with adducts give a by-product. In order to improve the yield and purity of target compounds, the starting material β-enaminonitriles was added to the system in drops. The reaction is new found, which has not been reported in literatures.