Visible Light Induced Halogenation And Nitration Of 8-Aminoquinolines In Continuous Flow

There have been a large number of reports disclosed not only the importance as pharmaceuticals,but also the usefulness of 8-aminoquinoline as a ligand for various organic transformations.Therefore,functionalization of 8-aminoquinolines,has been becoming an intensive research focus on synthetic chemistry.A continuous flow C5 halogenation of 8-aminoquinolines was developed using1,3-dihalo-5,5-dimethylhydantoin?DBDMH/DCDMH?as a cheap halogenation reagent.The bromination of N-8-quinolinyl-benzamide with DBDMH was selected as a model to screen the reaction parameters.Having identified the optimal reaction conditions for bromination of N-8-quinolinyl-benzamide with DBDMH,the substrate scope were then examined in continuous flow.C5 chlorination product was also obtained when replacing DBDMH to DCDMH and adding a certain amount of tert-butyl hydroperoxide?TBHP?.The reaction conditions were further optimized and the applicability of the present protocol for the scope of acyl motif was tested.A highly efficient,cheap and up-scaled C5 halogenation of8-aminoquinoline was developed.C5 and C7 nitration of 8-aminoquinolines were synthesized using NaNO₂ as nitro source and PhI?OOCCF₃?₂ as oxidant under blue LED irradiation.For a higher selectivity of C5nitration product,the reaction parameters were screened.Having identified the optimal reaction conditions for nitration of N-8-quinolinyl-benzamide with NaNO₂,the substrate scope were then examined.However,some substrates gave only C7 nitration product,rather than C5 nitration product,and some other provided both C5 and C7 nitration product.Based on these facts,C5 and C7 dinitration products was obtained through inproving the loading of NaNO₂ and PhI?OOCCF₃?₂.This methodlogy avoided using of trasition metal catalyst is the first photo induced nitration of 8-aminoquinolines,avoided using of trasition metal catalyst.