Photo-induced Benzylic Bromination And C5 Bromination Of Quinolines In Continuous Flow

Benzylic bromination and C-5 brominations of quinolines are very common reactions inorganic synthesis.Target products of benzylic and aromatic bromination reactions are important intermediates in organic chemistry.In this paper,the photo-induced benzylic mono/dibromination and C-5 bromination of 8-aminoquinoline amides in continuous flow have been developed.Section one focuses on photo-induced benzylic mono-and di-bromination in continuous flow,1,3-dibromo-5,5-dimethylhydantoin(DBDMH)is chose as the bromination reagent.Compared to traditional bromination in literatures,poisonous bromine(Br2)and carbon tetrachloride(CCl4)are avoided to use.And there are two bromine atoms in DBDMH and they can both react with toluene derivatives to get corresponding products.Surprisingly,not only the time of benzylic bromination reduce obviously,but the yield of product and selectivity of reaction improve significantly.Firstly,the optimal conditions of benzylic monobromination are explored,including reaction solvents,reaction time and quantities of bromide reagent.And the optimal conditions are obtained: 1.1 equiv,DBDMH,blue LED,CH3CN/DCM as the solvent,in continuous flow for 50 min.Then the substrates of toluene derivatives are investigated and get 11 corresponding target products in good yields.Most importantly,p-chlorotolueneis is chose as start material for a larger-scale experiment and still get 85% isolated yield.Secondly,the optimal conditions of benzylic dibromominationare are explored.Through screening the conditions of reaction,the optimal conditions are obtained: 2 equiv,DBDMH,blue LED,CH3CN/DCM as the solvent,in continuous flow for 70 min.In the section two,photo-induced C-5 bromination of 8-aminoquinoline amide is explored in continuous flow using DBDMH.Through screening of reaction conditions,the optimal conditions are determined: 0.2 mmol N-(quinolin-8-yl)benzamide;0.11 mmol DBDMH;dichloromethane as the solvent;incandescent lamp;in continuous flow for 30 min.With the optimal conditions in hand,the substrate scopes are investigated preliminarily.