Study On [3+2] Cycloadditions Between Pyrazolone-based Olefins And N,N'-cyclic Azomethine Imines

Nitrogen-containing heterocyclic compounds are a kind of valuable compounds,which are widely used in medicine,agriculture,catalysis,dyeing and other fields.Especially in the field of medicine,more than half of the micro-molecule drugs in the current drug database are nitrogen heterocyclic compounds.Therefore,this kind of compounds have attracted extensive attention from chemists and biologists.In this paper,the synthesis of novel spiropyrazolinone compounds by[3+2]cycloaddition reaction of pyrazolone-based olefins and N,N'-cyclic azomethine imines was studied.Firstly,the model reaction between pyrazolone-based olefins and N,N'-cyclic azomethine imines was established.The influence factors such as catalyst,solvent,temperature,reaction time and feed ratio were investigated,and the optimal reaction conditions were determined:the reactants were stirred in toluene solvent for2 h at 110?,with the feeding ratio of pyrazolone-based olefins/N,N'-cyclic azomethine imines/Ph CO₂H as 1:1.25:0.2.Secondly,under the optimum reaction conditions,32 novel spiropyrazolinone compounds were synthesized with excellent diastereoselectivity(up to 20:1 dr),low to excellent yield(17?98%),and general applicability.The effects of different substituents on electronic effects were also investigated.Finally,the relative stereoconfiguration of the product was determined by X-ray single crystal diffraction,and this[3+2]cycloaddition reaction mechanism was postulated.Therefore,for the first time,the[3+2]cycloaddition reaction of pyrazolone-based olefins and N,N'-cyclic azomethine imines was used to construct new spiropyrazolinone compounds,which could not only provide a reference for the subsequent cycloaddition reactions of pyrazolone-based olefins with other stable dipoles,but also based on the three continuous chiral centers contained in the products.It provides an objective material basis for the subsequent bioactivity evaluation,and provides the possibility for this kind of compound to become a new type of organic micro-molecule drugs in the future.