Study On Photochemical Reactions And Mechanism Of 1,4-dihydropyridine Derivatives

Organic photochemical reaction had the advantages of easy operation,high efficient and more environmental-friendly,controllable cost and so on.It was on the important position in the field of organic synthesis.Its unique mechanism could bring new reactions which was difficult to achieve by the thermal reaction.1,4-Dihydropyridine derivatives were widely used in the field of cardiovascular and cerebrovascular diseases as Ca⁺channel blockers.Its unique structure of 6?electron system lead to reactive chemical properties,such as[2+2]cyclization,oxidation and isomerization induced by light.The photochemical products of 1,4-dihydropyridines,such as 3,9-diazatetraasteranes,tetrahydrcyclobutas and pyridines,were found to have pharmacological activities of anti-HIV and antitumor and so on.Therefore,it was essential to investigate the photochemical reaction of 1,4-dihydropyridines systematically by organic photochemical method.The results will provide theoretical and experimental basis for its wider application in the future.To investigate the[2+2]photocycloaddition and photo oxidative rearrangement,ethyl-1,4-diaryl-1,4-dihydropyridine-3-carboxylate,2,6-dimethyl-4-aryl-1,4-dihydro-pyridine-3,5-dicarboxylate and 1-benzyl-1,4-dihydropyridine derivatives were chosed as the photochemical substrates.?1?Studies on the[2+2]photocycloaddition of 1,4-dihydropyridines.Ethyl-1,4-diaryl-1,4-dihydropyridine-3-carboxylate was choosed as the the substrates.The[2+2]photocycloaddition was investigated in the relationship of reaction conditions?type of light,wavelength and solvent?and substrate structures?electronic and steric effects?.The isolation and identification of photochemical products were the basis of the speculation of[2+2]photocycloaddition mechanism.Seven products of[2+2]photocycloaddition were obtained selectively in different condition of irradiation,including two kinds of 6,12-diazaterakishomocubanes,3,9-diazatetra-asteranes,3,6-diazatetraasteranes,tetrahydrcyclobutanes,3,9-diazatetracyclo dodecanes and 3,12-diazatetracyclododecane-dienes.The density functional theory wasused to investigate themechanisms ofphotocycloadditionof1,4-dihydropyridines.The mechanism was inferred that a syn-dimeric intermediate formed firstly and then an intramolecular[2+2]photocycloaddition occurred.The results show that[2+2]photocycloaddition was in two steps of intramolecular and intermolecular process through biradical intermediate.It is concluded that the orientation and stereoselectivity of the reaction were depended on the formation of the free radical intermediates in three excited states and the difficulty of the intersystem crossing.?2?Studies on the photooxidation-rearrangement of 1,4-dihydropyridines.2,6-Dimethyl-4-aryl-1,4-dihydropyridine-3,5-dicarboxylate,ethyl-1,4-diaryl-1,4-dihydro pyridine-3-carboxylate and 1-benzyl-1,4-dihydropyridine derivatives were choosed as the substrates.The photooxidation-rearrangement was investigated in the relationship of reaction conditions?wavelength,solvent,reaction temperature and oxygen?and the structures of products.The generations of the reaction were discussed to determine whether it could be used as a synthetic method of pyrrole derivatives.Under the irradiation,the 2,6-dimethyl-4-aryl-1,4-dihydropyridine-3,5-dicarboxylate was rearranged to 2,3-dihydropyrroles diastereoselectively,the ethyl-1,4-diaryl-1,4-dihydropyridine-3-carboxylatetopyrrolesandthe1-benzyl-1,4-dihydropyridine derivatives to pyrrolealdehydes and 1,2,3,4-tetrahydro-pyridines.Thestudiesonthethephotooxidation-rearrangementof1,4-dihydropyridines could provide a new theoretical basis and an experimental method for the synthesis of functionalized pyrroles and 2,3-dihydropyrroles with higher diastereoselectivity.During the studies on the photochemical reaction of 1,4-dihydropyridine,76 new proudcts were obtained and has not been reported in literatures.There are 56 novel cage compounds,7 novel tetrahydrcyclobutas,10 novel 2,3-dihydropyrroles,2 novel pyrroles and 1 noval 1,2,3,4-tetrahydropyridine which were characterized by ¹H and¹³C NMR spectroscopy,HRMS and X-ray diffraction.The[2+2]photocycloaddition and photooxidative-rearrangement of 1,4-dihydropyridines could be used as the efficient and stereoselective synthesis methods of cage compounds and pyrroles.