Copper Catalyzed Thiolation Of Arylsulfonylhydrazide And Arenes C-H Bond

Arylsulfonylhydrazides are solid compound which have advantages such as odorless,environmentally friendly,easy to prepare,stable and low in toxicity.According to literature reports,arylsulfonylhydrazides as thiolation reagent have wide substrate scope,and can be used to synthesize a series of novel aryl sulfides,which have wide application prospects in organic synthesis.Based on the previous studies,the sulfonylation reaction of arylsulfonylhydrazide have been extensively studied in this paper.The main research contents are as follows:Firstly,a copper-catalyzed C-H thiolation of electron-rich arene with arylsulfonylhydrazide was investigated to prepare bis-thiolation derivatives.The optimal reaction condition are as follows:arene?0.3 mmol?,arylsulfonylhydrazide?0.6 mmol?,Cu?OTf?₂?0.2 mmol?,DCE?2 mL?,HOAc?1 mL?and 80 ^oC for 8 h.The method has wide substrate scope and good functional group tolerence,and various arylsulfonylhydrazides and electron-rich arene can rationally participate in the reaction.23 kinds of diaryl thioether derivatives were obtained in 15-93%yields.In addition,the possible reaction process of this reaction is confirmed by the previous reports and designing experiments combined with the existing relevant literatures.The mechanism research shows that this reaction path may involve a free radical formation and copper-catalyzed circulation;diaryl disulfide?RSSR?and thiosulfate?RSO₂SR?are the main thiointermediates in this conversion process.Secondly,mono-and bis-thiolation benzoheterocycles were synthesized by direct thiolation of benzoheterocycles with arylsulfonylhydrazides in the presence of copper.The optimum condition are as follows:benzoheterocycle?0.3 mmol?,arylsulfonylhydrazide?0.8 mmol?,Cu?OTf?₂?0.2 mmol?,toluene?1 mL?,H₂O?0.1mL?,HOAc?2 mL?at 110 ^oC for 8 h.Both electron-donating and electron-withdrawing groups substituted arylsulfonylhydrazides have good yield.However,the electronic properties of indole have a great influcnce on this reaction.When there are strong electron-withdrawing groups?7-NO₂,5-NO₂,4-CN?in the 4-7position of indoles,the product is a monosulfide product in the C-3 position of indoles.In particular,this reaction system is also suitable for benzofuran?X=O?and benzothiophene?X=S?.23 mono-or bis-sulfenyl benzoheterocyclic derivatives were obtained in 14-87%yield.The system not has good substrate scope and good functional group tolerence,but also has the characteristics of environmental friendliness?no base,no ligand?,simple operation,mild reaction conditions.Finally,it was found that thiosulfate?RSO₂SR?is the key thiointermediate in the conversion process.Lastly,a Cu-catalyzed sulfidation of alcohols and arylsulfonylhydrazides was investigated.A series of arylsulfinates were simply and effectively prepared with air as oxidant.The optimal reaction condition:ethanol?2 ml?,arylsulfonylhydrazide?0.6mmol?,Cu?OTf?₂?0.1 mmol?,at 80 ^oC for 8 h.The method has wide substrate applicability and high compatibility with functional groups,and has good yield no matter the electron-donating or the electron-withdrawing group substituted sulfonylhydrazides.Similarly,various alcohols also have good substrate adaptability,such as methanol,ethanol,n-propanol,n-butanol,isopropanol,tert-butanol and benzyl alcohol.The yield of products was obtained in 27-73%.In addition,a gram-scale reaction was conducted and 1.6 g of the target product was obtained in 58%yield.Finally,arylsulfinate was used as a multifunctional new sulfur source,and the product derivative reaction took place successfully.The experimental analysis shows that the reaction is conducted through two stages both radical formation and copper catalytic cycle,and arylsulfinic acid is the main esterification intermediate of the reaction.In summary,based on copper-catalyzed sulfidation of arylsulfonylhydrazide,a series of novel arylthioether?hetero?arenes and arylsulfinates were prepared from simple?hetero?arene molecules via direct C-H bond activation,which greatly supplemented and increased the formation method of C-S bond.