Studies On Synthesis And [2+2] Photocyclization Of 1,4-and 1,2-dihydropyridine Derivatives

Dihydropyridines is an important class of nitrogen-containing heterocyclic compounds.Among them,1,4-dihydropyridines and 1,2-dihydropyridines are the two most common isomers,and the position of the double bond in the molecules has an important influence on its pharmacological activitys and applications.1,4-Dihydropyridines are often used as calcium channel inhibitors in the treatment of cardiovascular and cerebrovascular diseases,and 1,2-dihydropyridines are important raw materials for the synthesis of active backbones of many natural alkaloids.Therefore,the systematically studies on the influence of the double bond position of dihydropyridine on its synthesis and[2+2]photocyclization has important theoretical and practical significance.In this dissertation,after studying the difference in the synthesis of 1,4-dihydropyridine and 1,2-dihydropyridine derivatives,the[2+2]photocyclization of this two kinds of dihydropyridines was systematically studied.And the reason for the difference in[2+2]photocyclization of 1,4-dihydropyridines and 1,2-dihydropyridines was theoretically studied.The results of synthesis and[2+2]photocyclization studies of 1,4-dihydropyridine and 1,2-dihydropyridines will provide theoretical and experimental guidance for further explorations on the chemical synthesis based on this two types of dihydropyridine skeletons and the application in pharmacological activity of dihydropyridines.Synthesis of 1,4-dihydropyridine and 1,2-dihydropyridines.The multicomponent synthesis method based on the Hantzsch reaction was used to synthesize the two kinds of dihydropyridines.Namely,using ethyl propiolate,aldehyde and amine as the materials,the effects of reaction solvent,catalyst and reaction temperature on the yields was studied.The optimized reaction conditions for the 1,4-dihydropyridines and 1,2-dihydropyridines were subsequently determined,10 1,4-dihydropyridine derivatives and 10 1,2-dihydropyridine derivatives were synthesized.The possible reaction mechanism was discussed through calculating the reaction energy barriers of the key intermediates in the reaction process using density functional theory(DFT)method.Studies on the[2+2]photocyclization of 1,4-dihydropyridines and 1,2-dihydropyridines.The photophysical properties of 1,4-dihydropyridine and 1,2-dihydropyridine derivatives were studied by the measurement and analysis of their UV-visible spectroscopy and fluorescence spectroscopy.The[2+2]photocyclization of 1,4-dihydropyridines and 1,2-dihydropyridines in liquid phase was investigated by selecting diethyl-1,4-diphenyl-1,4-dihydropyridine-3,5-dicarboxylate and diethyl-1,2-diphenyl-1,2-dihydropyridine-3,5-dicarboxylate as the reaction substrate.In order to find the key influencing factors,the effects of the solvent and the wavelength of the irradiation light on the reaction products and reaction rate were studied.The photochemical reactivity and the difference of 1,4-dihydropyridine and 1,2-dihydropyridine derivatives in[2+2]photocyclization was investigated by the method of time-dependent density functional theory(TDDFT).In this dissertation,15 novel compounds were synthesized during the synthesis and the[2+2]photocyclization of 1,2-dihydropyridine and 1,4-dihydropyridines,one of them was 1,4-dihydropyridine derivative,8 were 1,2-dihydropyridine derivatives,and6 were photocyclic reaction products.All the structures of new compounds were confirmed by ¹H NMR,¹³C NMR and HRMS.