Construction Of Nitrogen-containing Heterocycles Bearing Bisphosphonates By Tetraethyl Ethenylidenebisphosphonate (VBP) And Azomethine Imines

As a broad-spectrum intermediate,VBP can be used as dienophile to obtain a variety of bioactive heterocycles bearing bisphosphonates.It's one of the important methods to obtain 1,3-dipoles by pyrazole ketones with carbonyl compounds condensation dehydration getting unstable azomethine imine.The azomethine imine formed by the condensation dehydration of a series of aromatic aldehyde compounds,isatin and its derivatives with pyrazole ketones.On the one hand,we get a series of potential biological activitydinitrogen-fused heterocycles bearing bisphosphonates by [3+2]-dipolar cycloaddition reaction of azomethine imine with tetraethylethenylidenebisphosphonate?VBP?in the presence of Cu I in toluene media.On the other hand,we get a series of potential biological activitydinitrogen-fused 3,3-disubstituted oxindole derivatives heterocycles bearing bisphosphonates by rearrangement and Michael Addition reaction of isatin N,N'-cyclic azomethine imine 1,3-dipoles with tetraethylethenylidenebisphosphonate?VBP?in the presence of K₂CO₃ in THF media.The clearly proposed mechanism is in line with the experimental data.The targeted molecular are fully characterized by ¹H NMR,³¹P NMR,¹³C NMR,HSQC,HMBC,HRMS.Each individual hydrogen atoms in a compound structure skeleton got clear attribution and most of the carbon atoms.Enrich and expand the range of substrates that carbonyl compounds and pyrazole ketones generated in the form of azomethine imine by condensation dehydration,and prompted the reaction with VBP,further enrich the VBP participation the reaction of [3+2]-dipolar cycloaddition and Michael addition reaction with the azomethine imine generated by dehydrated.The raw materials is easy to be obtained,the cost is low and the operation is simple and the yield is good.Adopted metal ions catalytic,the simple operation,mild conditions,low consumption,high yield,easy separation.Observed and isolated for the first time of the rearrangement product intermediates,and characterization of rearrangement product structure,thus the reaction mechanism was proposed based on the experiment facts,supportting the previous reports on the reaction mechanism of prediction.For individual target compounds,after the reaction,removing the solvent,direct precipitation in the form of crystal,especially easy to separate,avoid the column chromatography.If these compounds have good biological activity,witch will be detected a great purpose in the industry.