Synthesis Of Thioether Compounds Of Flavonoids And Imidazo Pyridines

Nowdays,sulfur compounds have been widely used in materials,chemicals,drugs and other fields.Therefore,the preparation methods of sulfide has always been one of the hotest research spots,especially the C-S bond construction method.Because C-S bonds are widely found in drug molecules,the search for efficient and concise methods for constructing C-S bonds is very valuable in drug synthesis.Flavonoids and imidazo[1,2-?]pyridine compounds are widely found in natural products.Among them,the flavonoids are mainly bio-active natural drug molecules,through the study,it is found that flavonoids with antioxidant,improve blood circulation,lower cholesterol,promote wound healing and pain and so on.Imidazo[1,2-?]pyridine compounds are also more prevalent in natural products,especially imidazo[1,2-?]pyridine derivatives also have a wide range of biological activities such as antiviral,antitumor,antiparasitic,Anti-microbial agents,fungicides,anti-inflammatory,hypnotic effects.Therefore,the synthetic methods of making flavonoids and imidazo[1,2-?]pyridine compounds has been one of the hotspots in the field of pharmaceutical chemistry.In recent years,the relevant pharmacological journals have reported that flavonoid thioether compounds and imidazo[1,2-?]pyridine thioether compounds have potential biological activities,and these two kinds of compounds have a high medicinal value.At present,although these compounds can be obtained by traditional Chinese medicine extraction or traditional synthesis method.However,the extraction of traditional Chinese medicine to obtain such compounds is limited in quntity and the process is cumbersome,the traditional synthesis method is also complicated.Therefore,searching for a simple and effective method to synthesize flavonoids and imidazo[1,2-?]pyridine sulfide compounds has been of great concern.Based on the reports from other research groups,we have synthesized a series of flavonoids and imidazo[1,2-?]pyridine compounds as reactants,then we developed several simple and efficient ways to make flavonoids and imidazo[1,2-?]pyridine thioether derivatives.(1)In this paper,sodium benzenesulfinates was chosen as aryl sulfur sources,via C-H functionalization process,the sulfenylation methods of flavonoids and imidazo[1,2-?]pyridine were developed,all reactions were successfully carried out.It was proved that the sulfenylation method is environmentally friendly and yields were high.(2)In order to find cheap,easy,environment-friendly,high yield and non-toxic sulfur source as sulfur agents,this paper once again try to use a series of inorganic sulfur salt as a sulfur source,in order to achieve heterocyclic compounds thioetherification.After repeated experiments,we chose inorganic elemental sulfur and sodium thiosulfate as sulfur sources.Reactions of three components(iodobenzene or haloalkanes,elemental sulfur or sodium thiosulfate,imidazo[1,2-?]pyridine)imidazo[1,2-?]thioesters were developed via C-H functionalization in the presence of transition metal cuprous iodide,a series of heterocyclic compounds of the aryl thioether and alkyl sulfide were obtained.The method has wide application affording high yields.(3)At the same time we tried to use alcohols instead of halogenated alkanes as starting materials,we found in the presence of iodine and triphenyl phosphine,the reactions proceeded well with inorganic sulfur element or sodium thiosulfate as sulfur source,giving imidazo[1,2-?]pyridine thioether molecules in higher yields.In the paper,three new methods for the synthesis of aryl and alkyl sulfide of heterocyclic compounds have been discovered.These methods have more advantages than traditional methods.The advantages are: simple operation,wide application range,low cost of raw materials,less impurities and high yield.Therefore,these methods not only have high industrial value,but also can provide a big support for the preparation of future heterocyclic thioether derivatives of biological activitoes in the future.