Study On Cyclization Reaction Of Substituted Chromones And Substituted Cyclopropanes

Chromeno[2,3-b]pyridine compounds are a class of heterocyclic compounds with important biological activities,and many derivatives containing chromeno[2,3-b]pyridine have been widely used in clinical treatments.In addition,chromeno[2,3-b]pyridine compounds have also found applications in special photo organic material syntheses.Based on this,the investigation on synthetic methods of chromeno[2,3-b]pyridine compounds has become a recent research hotspot.The findings suggest that chromones bearing two nucleophilic site sites readily undergo[3+3]cycloaddition with electrophiles to give the chromeno[2,3-b]pyridine core.Additionally,multisubstituted D-A cyclopropanes as three carbon synthons can be used to synthesize a diverse array of opening-chain,carbocyclic,or heterocyclic compounds,especially playing a key role in cycloaddition reactions via ring opening.On the basis of studies of substituted chromones,substituted cyclopropanes,and heterocycles in this work,using 2-aminochromenones as substrates,two synthetic routes of substituted chromeno[2,3-b]pyridines were designed,2-phenyl-5H-chromeno[2,3-b]pyridine-5-one derivatives and 3-hydroxy-2-（2-hydroxyphenyl）-4-phenyl-5H-chromeno[2,3-b]pyridine-5-one derivatives were successfully synthesized.Additionally,the cyclization reaction of multisubstituted D-A cyclopropanes and substituted β-nitrostrenes was investigated for the synthesis of multisubstituted cyclopentene derivatives.The first part:The synthesis of 2-phenyl-5H-chromeno[2,3-b]pyridin-5-one derivatives was investigated.First,a series of conditions screening optimizations using substituted chromones and substituted cinnamaldehydes as reaction substrates,the optimal conditions were identified and DABCO was employed as the basic promoter.Under the optimal conditions,eighteen 2-phenyl-5H-chromeno[2,3-b]pyridin-5-one derivatives were synthesized in 60-81%yields.Then,a three component reaction involving substituted chromenes,substituted benzaldehydes,and acetaldehydes was investigated to synthesize 2-phenyl-5H-chromeno[2,3-b]pyridin-5-one derivatives,which were optimized after condition screening to determine the optimal conditions,and triethylamine was used as basic enhancer.Sixteen 2-phenyl-5H-chromeno[2,3-b]pyridin-5-one derivatives were obtained in 71-81%yields.All target products were characterized by infrared,NMR hydrogen spectroscopy,NMR carbon spectroscopy,high-resolution mass spectrometry,and the stereostructures of the four compounds were determined by single-crystal X-diffraction analysis.The second part:The synthesis of 3-hydroxy-2-（2-hydroxyphenyl）-4-phenyl-5Hchromeno[2,3-b]pyridin-5-one derivatives was investigated.Using substituted chromenes and substituted benzaldehydes as reaction substrates,the optimal conditions were obtained after a series of conditions screening optimization.Under the optimized conditions,the reaction was performed with DBU as the basic promoter,resulting in 23 target products in 62-78%yields,which were all characterized by infrared,NMR hydrogen spectroscopy,NMR carbon spectroscopy,high-resolution mass spectrometry,and the stereostructures of the two compounds were determined by single-crystal X-diffraction analysis.The third part:The synthesis of polysubstituted cyclopentene derivatives was carried out.Substituted 1,1-dicyanocyclopropanes and substituted β-Nitrostyrene were used as the reaction substrates,after a series of conditions selection optimizations,the optimal conditions were obtained by using piperidine as the base to perform the reaction,leading to the final 16 target products in 60-72%yields,which were all characterized by infrared,NMR hydrogen spectroscopy,NMR carbon spectroscopy,high-resolution mass spectrometry,and the stereostructure of one compound was determined by single-crystal X-diffraction analysis.