The Synthesis Of New Dihydropyrimid-inone Derivatives Via Multicomponent Reaction

Multicomponent reaction with high atom economy, high reaction steps and process economics, is a fast, efficient, green, large-scale synthesis strategy towards biologically active of small organic molecules. Multicomponent reactions have been widely used in the synthesis of natural products and organic activitic small molecules, pharmaceuticas and pesticide development and construction of new materials. The dihydropyrimidinone and its derivatives have been demonstrated to have anti-tumor, anti-viral, anti-bacterial as well as anti-inflammatory, and many other biological activity, thus they have been widespread concerned. In this thesis, we mainly studied the synthesis of a new class of dihydropyrimidone derivatives using a multicomponent reaction strategy via molecular iodine and chiral phosphoric acids as the catalyst, respectively. The main content of the thesis is as follows:First, the progress towards to the synthetic method of dihydropyrimidinone derivatives in over the past decade was reviewed, including the progress of synthetic methods for the racemic dihydropyrimidinone derivatives and catalytic asymmetric synthesis for the optical dihydropyrimidinone derivatives.Second, we studied the molecular iodine catalyzed the three-component reaction of aromatic aldehydes, aliphatic aldehydes, and monosubstituted urea to synthesis of new dihydropyrimidinone derivatives.22new dihydropyrimidone derivatives were synthesized in moderate to excellent yield under the optimal conditions with10mol%of molecular iodine as a catalyst, and acetonitrile as solvent and reflux reaction. The structure of product4a was confirmed from X-ray single crystal analysis. This method has some advantages, such as high efficiency, good selectivity, mild reaction conditions, and operativity easily.Once again, we synthesized7spirocyclic chiral phosphoric acid and binaphthyl phosphoric acid derivatives. We studied the applycation of these chiral phosphoric acid catalyst in asymmetric catalyzed-three-component reaction of aromatic aldehydes, aliphatic aldehydes and monosubstituted urea. Through the optimization of reaction condition, as well as the bidirectional control of the catalyst and substrate, we found that optically active dihydropyrimidone derivatives with up to77%ee and up to80%yield could be obtained under the optimum reaction conditions with10%chiral spirocyclic phosphate5a as a catalyst, toluene as solvent, and at room temperature. This is the first asymmetric catalysis research to this new type of multicomponent reaction.Finally, we synthesized a1,1-cyclopropane amino-ketone derivatives7. The stereospecific Z-product7could be obtained in a yield of63%in the presence of DBU in dichloromethane from α-amino aryl ketone and the styryl diphenyl sulfonium salt of trifluoromethanesulfonic acid. The products were identified by X-ray single crystal analysis. This is a highly stereoselective synthesis of1,1-cyclopropane aminoketone derivative.