Studies On The Construction Of Small Molecular Nitrogen-containing Heterocyclic Units In Medicines

Heterocycles containing the nitrogen are the basic skeletons of numerous natural organic compounds and synthetic medicines with important biological activities.In recent years,heterocycles with the nitrogen are used widely as important pharmacophores in the design and synthesis of the innovative medicines,a large number of organic compounds with the nitrogen were synthesized for the researches of biological activities.Based on our previous researches of the preparation of heterocyclic compounds containing the nitrogen,in this paper,the synthesis of 2,4,6-triarylpyridine derivatives,1-nitroindolizine derivatives and benzoxazine derivative from substituted ?-nitrostyrenes and substituted salicylic aldehydes has been developed.The first part:2,4,6-trisubstituted pyridines were synthesized via one-pot reaction of?-nitrostyrenes,pyridine quaternary ammonium salts and ammonium acetate in the acidic conditions.Eighteen products were obtained under the optimized reaction conditions in yields of 69-85%.All compounds were characterized by NMR,IR and HRMS spectroscopy.One of the compounds was subjected to single crystal X-ray diffraction analysis to determine the structure.The second part:A highly selective method was developed for the synthesis of 1-nitroindolizine derivatives via the DBU-mediated cycloaddition reaction of ?-nitrostyrenes and pyridine quaternary ammonium salts.1-Nitroindolizine derivatives were gained in 70-90%yields.All compounds were characterized by NMR,IR and HRMS spectroscopy.The single crystal structure of one 1-nitroindolizine was confirmed by X-ray diffraction method.The third part:Benzoxazine derivatives were synthesized via one-pot reaction of substituted salicylicaldehydes and ammonium acetate in the presence of potassium carbonate.Seven products were synthesized under optimized the reaction conditions in 70-80%yield.Then,an pseudo four-component reaction of substituted 2-hydroxybenzaldehydes,ammonium acetate and different dialkyl but-2-ynedioates for the preparation of epiminodibenzo[b,f][1,5]dioxocin-13-yl-but-2-enedioates was developed.Eight products were yielded under the optimized reaction conditions in 60-83%.All compounds were characterized by NMR,IR and HRMS spectroscopy.The single crystal structures of two desired products were confirmed by X-ray diffraction method.