Study On Synthesis Of Nitrogen Heterocycle And Indene Derivatives

Many drugs and natural product molecules contain the basic skeleton of nitrogen heterocycle or indene.It has always been a research hotspot in organic synthesis to develop efficient and green methods to synthesize such compounds.Because of their unique physiological and pharmacological activities,imidazole,quinoxaline and indole derivatives have been widely used in many fields.Although lots of related research works have been reported,some shortcomings still exist,and further research is needed.In this paper,we report efficient methods for the synthesis of nitrogen heterocycles and indene derivatives,and the main contents are as follows:（1）N-alkyl-2-thio（selenyl）imidazole derivatives were obtained via a"one-pot"reaction of N-alkylimidazole and diaryl disulfide（diselenide）promoted by the I₂/DMSO catalytic oxidation system.Using the reaction of N-methylimidazole and diphenyl disulfide as a model reaction,the reaction conditions were systematically optimized.Under these optimized conditions,a series（32 examples）of 2-thio（selenyl）-N-alkylimidazole derivatives were synthesized in high yields up to 99%.A gram-scale reaction was studied to explore the industrial application prospects of this reaction.Compared to previous methods,this method has the advantages of no need of transition metal catalysts or metal reagents,simple opera tion,readily available raw materials and green efficiency,providing an efficient route to N-alkyl-2-thio（selenyl）imidazole derivatives.（2）3-Aryl（alkanoyl）-2-hydroxyquinoxaline derivatives were obtained via the reaction of 2-hydroxyquinoxaline anda-ketoacids in the presence of ammonium persulfate（（NH₄）₂S₂O₈）.Using the reaction of 2-hydroxyquinoxaline and phenylglyoxylic acid as a model reaction,the reaction conditions were systematically optimized.Under the optimal conditions,a series（21 examples）of3-aryl（alkanoyl）-2-hydroxyquinoxaline derivatives were synthesized.A gram-scale reaction was studied to explore the industrial application prospects of this reaction.Using 3-aroyl-2-hydroxyquinoxaline as a raw material,3-benzoyl-2-（4-methylpiperazine）quinoxaline which shows good antitumor activity was successfully prepared via a more convenient pathway with higher yield.Compare to the previous works,this method has the advantages of simple operation,easy-to-obtain raw materials and wide functional groups tolerance,providing a simple and convenient methods strategy for the synthesis of 3-acylated-2-hydroxyquin oxaline derivatives.（3）This paper developed an efficient method for the synthesis of3-trifluoromethyl-2-hydroxyquinoxaline via direct trifluoromethylation of2-hydroxyquinoxaline promoted by ammonium persulfate（（NH₄）₂S₂O₈）.The reaction of 2-hydroxyquinoxaline and sodium trifluoromethyl sulfinate was used as a model reaction to optimize the reaction conditions.Under the optimal conditions,a series（19 examples）of 3-trifluoromethyl-2-hydroxyquinoxalines were synthesized with high yields up to 89%.A gram-scale reaction was studied to explore the industrial application prospects of this reaction.Compared to previous methods,this method has some advantages such as simple operation,high yields and wide functional groups tolerance,providing an efficient and convenient route to 3-trifluoromethyl-2-hydroxyquinoxaline compounds.（4）3-arylthioindoles were obtained via the sulfonation of indole derivatives with diaryl disulfides catalyzed by cesium hydroxide（CsOH.H₂O）.Using the reaction of indole and diphenyl disulfide as a model reaction,the reaction conditions were systematically optimized.Under the optimal c onditions,a series（24 examples）of3-thioarylindole derivatives were synthesized.And using 3-arylthioindole derivatives as raw material,the anti-HIV active molecule L-737,126 was successfully synthesized.This reaction can be carried out in H₂O without adding any other additives.Compared to previous methods,this method has the advantages of mild reaction conditions,simple operation and reuseable reaction system,providing a gr een and efficient method for the preparation of 3-thioarylindole derivatives.（5）This paper developed an efficient method for the synthesis of benzofulvene via the cesium hydroxide catalyzed condensation of indenes with aromatic aldehydes.The reaction conditions were optimized using the reaction of indene and benzaldehyde as model reaction.Under the optimal conditions,13 examples of mono-substituted benzofulvene compounds and 6 examples of di-substituted benzofulvene compounds were synthesized.Compared to the previous method,this method uses ethanol as green solvent,and the reaction can be carried out at room temperature with good chemical selectivity.In addition,phase transfer catalysts,excess alkalis or other additives are not necessary in this method,providing a fast and efficient method for the preparation of benzofulvene compounds.（6）As a kind of important precursors,propargylamine compounds can be synthesized into a variety of complex nitrogen heterocyclic derivatives through cyclization reactions.In this chapter,palladium-copper nanowire catalyst was used to catalyze the formation of propargylamines via the“one-pot”reaction of secondary amines,terminal alkynes and aryl（alkyl）aldehydes.T he reaction conditions were systematically optimized using the reaction of piperidine,benzaldehyde,and phenylacetylene as a model reaction.Under the optimal conditions,a series（30examples）of propargylamine compounds were synthesized in high yields up to 99%.A gram-scale reaction was studied to explore the industrial application prospects of this reaction.The reaction can be carried out in a solvent-free condition.The catalyst showed high catalytic activity after recycling for 5 times.And the only by-product is H₂O,meeting the requirements of green chemistry.This method provides an efficient,economical and green way for the synthesis of propargylamines.