Study On The Green Synthesis Of New 3,4-dihydro Pyrimidinone Derivatives

Dihydropyrimidinone derivatives(DHPMs) show important biological and pharmacological activities. They are medicinally important as calcium channel blockers, antihypertensive agents and ?1a-antagonists. In addition, they exhibit a wide range of medicinal applications in antibacterial, antivirus, anticancer, antimalarial and antiphlogistic fields. The classical method for the synthesis of DHPMs was the Biginelli reaction, involves the one-pot condensation of an aldehyde, a 1,3-dicarbonyl compound and urea in the presence of HCl. Thus, the Biginelli reaction attracted considerable attention. While the researchers explored the reaction conditions and improved synthetic methods, some Biginelli-like reactions have also been reported and many new 3,4-dihydropyrimidinone derivatives have been synthesized. It broadened the reaction substrates remarkably.In this thesis, the progress towards the synthesis of N(1)-substituted 3,4-dihydropyrimidin-2-one derivatives and 4,6-diaryl-3,4-dihydropyrimidin-2(1H)-ones derivatives was summarized. It proposed the new method for the synthesis of N(1)-substituted 3,4-dihydropyrimidin-2-one derivatives and 4,6-diaryl-3,4-dihydropyrimidin-2(1H)-ones derivatives. The research results are presented as follows:Twenty-eight N(1)-substituted 3,4-dihydropyrimidin-2-one derivatives were synthesized through a three-component one-pot reaction of an aromatic aldehyde, an ethyl acetoacetate(methyl ester) and a monosubstituted urea catalyzed by aluminium p-toluenesulfonate or tin tetrachloride at 80 oC under solvent-free conditions. Two reaction systems were carried out without solvent. The experimental results indicate the advantages of them are simple operation, short reaction time, high yields, active and inexpensive catalyst. aluminium p-toluenesulfonate is a recyclable catalyst.Twenty-six 4,6-diaryl-3,4-dihydropyrimidin-2(1H)-ones derivatives were synthesized through a three-component one-pot reaction of an aromatic aldehyde, an acetophenone and a urea catalyzed by aluminium p-toluenesulfonate or tin tetrachloride at 90 oC under solvent-free condition. Compared with the reported methods, two reaction systems have the advantages of mild condition, short reaction time, high yields, active and inexpensive catalyst. Aluminium p-toluenesulfonate is a recyclable catalyst.All products were identified by 1H NMR, 13 C NMR, IR and MS. The crystal structures of the three compounds were analyzed by single crystal X-ray crystallographic analysis.