Studies On The Cycloaddition Reaction To Construct Nitron Containing Quinone Polyheterocycle Compounds Base On 1,4-naphthoquinone

1,4-naphthoquinone and its derivatives are found to existed in a wide range of drugs and dyes et al.Quinone structure fused-heterocycle compounds can be found in a large number of biological molecular with anticancer,antimicrobial and antiinfectire.Synthesis of quinone structure polyheterocycle compounds have attracted consider attention in organic chemistry via cycloaddition/oxidation reaction based on 1,4-naphthoquinone.In this article,I₂-promoted multicomponent reaction for the efficient synthesis of benzo[f]pyrido[1,2-a]pyridine-6,11-dione derivatives have been developed.A novelmethodhavebeendevelopmentforsynthesisof naphtho[1',2':4,5]imidazo[1,2-a]pyridine-5,6-dione derivatives via Pd?OAc?₂mediated and several naphtho[2',3':4,5]imidazo[1,2-a]pyridine-6,11-dione derivatives were constructed by KI/CuCl₂·2H₂O catalyzed via cycloaddition reaction.A series of 53 compounds were designed and synthesized,among which 27 of these are new compounds.It could be described as the following four parts.I₂ promoted one pot multicomponent reaction for synthesis of a series of benzo[f]pyrido[1,2-a]indole-6,11-dionederivativesfromquinone,?-bromoacetophenone with pyridine via nucleophilic addition/cyclization/oxidation reaction.We have developed a efficient method to afford the target product at ambient condition.The reaction was discussed and the reaction condition hanve been surveyed.The results showed that the optimal parameters were as following:2 equivalents iodine,1,4-naphthoquinone and?-bromoacetophenone with 3 equivalents pyridine,CH₃CN as solvent under60?.A series of 27 products were obtained in 24-95%yields.A series of benzo[f]pyrido[1,2-a]indole-6,11-dione derivatives were synthesized from 1,4-naphthoquinone,acetophenone and pyridine via I₂mediated SP³ C-H functionalization of methyl ketones.The results showed that the optimal reaction conditions were as follows:1.5 equivalents acetophenone,2 equivalents pyridine and 2 equivalents I₂ was refluxed at 140?for 1h,the reaction mixture was stirred in CH₃CN at 0?for 5 h,then1,4-naphthoquinone and 2 equivalents pyridine was added,the reaction mixture was stirred for 8 h at 60?.A series of 23 products in 31-93%yields.Pd?OAc?₂/Cu?OAc?₂ catalyzed tandem nucleophilic addition/cyclization/oxidationsequencewasdevelopedforthesynthesisof naphtho[1',2':4,5]imidazo[1,2-a]pyridine-5,6-dionederivativesfrom1,4-naphthoquinone and 2-aminopyridine.The results showed that the optimal parameters were as follows:7.5 mol%Pd?OAc?₂,1 equivalent Cu?OAc?₂,2equivalents 2-aminopyridine,HOAc as solvent,a series of 11 products in10-73%yields.KI/CuCl₂·2H₂O catalyzed tandem electrophilic substitution/nucleophilic substitution/oxidation sequence was designed for the synthesis of naphtho[2',3':4,5]imidazo[1,2-a]pyridine-6,11-dionederivativesfrom2-?2-aminopyridyl?-1,4-naphthoquinone.The results showed that the optimal reactionconditionswereasfollows:amixtureof2-?2-aminopyridyl?-1,4-naphthoquinone,1 equivalent KI,2 equivalents CuCl₂·2H₂O,2 equivalents Cs₂CO₃ with 2 mL DMF at 120?for 6 h.A series of 7 products in 58-93%yields.