Synthesis Of Selenylated Aromatic Heterocyclic Derivatives Under The Condition Of Selectfluor

Aromatic heterocyclic compounds widely exist in natural products,which have anti-cancer,anti-microbial,antibacterial and anti-inflammatory,anticoagulant,antiviral and other biological activities,and is one of the important skeleton of many drugs.At the same time,selenium is one of the essential trace elements of human body.Organic selenides containing heterocyclic units have unique biological activities,such as anti-tumor,anti-aging,antioxidant and so on.Selectfluor reagent is a kind of fluorination reagent and oxidant with excellent properties.It has the advantages of high reactivity,safety and low toxicity,etc.,and has been used widely in organic synthesis in recent years.Therefore,it is of great significance to explore a green and efficient approach to synthesize aromatic heterocyclic selenylated derivatives.In this paper,a series of aromatic heterocyclic selenylated derivatives were synthesized by the action of N-（4-methoxyphenyl）-N-methylpropanamide or o-hydroxyleneamine ketone with diaryl diselenides under the condition of Selectfluor reagent.The advantages of this synthetic approach are mild reaction conditions,wide substrate range and green environment.The specific contents are as follows:（1）Synthesis of arylselenylated spiro[4.5]trienone derivatives under the condition of Selectfluor reagentThe reaction of N-（4-methoxyphenyl）-N-methylpropanamide and diphenyl diselenide is used as the template reaction.The reaction conditions are optimized,and the optimal conditions are obtained:the molar ratio of N-（4-methoxyphenyl）-N-methylpropanamide and diphenyl diselenide is 1:1,1.0 equiv Selectfluor reagent as oxidant in CH₃CN at 40℃for2 h,the yield can reach 90%.Using the best reaction conditions,twenty-one3-arylselenylated spiro[4.5]trienone derivatives are synthesized successfully.When Cu Br is used as a catalyst under the standard conditions,nine 3,4-diarylselenylated spiro[4.5]trienone derivatives are also synthesized.All of their structures were confirmed by IR,NMR and HR MS.The reaction mechanism is also speculated to be a free radical reaction by controlled experiments.The advantages of the reaction are mild conditions,simple operation and high yield.（2）Synthesis of 3-arylselenylated chromone derivatives under the condition of Selectfluor reagentThe reaction of o-hydroxyphenyleneamine and diphenyl diselenether is employed as the template reaction,the conditions including the type of oxidant,the amount of oxidant,the type of solvent,the molar ratio of substrates,temperature and time are optimized.The optimal conditions are obtained:the molar ratio of o-hydroxyphenylenone and diphenyl diselenide is 1:1.5,1.0 equiv Selectfluor reagent as oxidant in CH₃CN at 40℃for 2 h,and the yield was 87%.Twenty-nine 3-arylselenylated chromone derivatives are synthesized under the optimal conditions,and their structures were elucidated by IR,NMR and HR MS.The reaction mechanism may be ionic reaction by controlled experiments.This method has the advantages of mild reaction condition and high yield.（3）Synthesis of 3-halogen chromone derivatives under the condition of Selectfluor reagentThe reaction of o-hydroxyphenyleneamine with Selectfluor reagent is used as the template reaction,and the influencing factors of the reaction are investigated.The optimal reaction conditions are obtained as follows:the ratio of o-hydroxyphenyleneamine and Selectfluor reagent is 1:1,in Me CN for 2 h at room temperature,and the yield can reach80%.Under the optimal conditions,30 halogen chromone derivatives are synthesized by the reaction of o-hydroxyphenyleneamines,Selectfluor reagents with different halogenated copper salts,and their structures were confirmed by NMR,IR and HR MS.The reaction mechanism is also assumed to be ionic reaction by controlled experiments.This method has the advantages of mild reaction conditions,wide substrate range,high yields and green environment.