Study On The Nucleophilic Ring-opening Reaction At C5 Position Of Amidooxazoline

β-amide compounds are important congeneric of organic compounds,which have a wide range of applications in medicine,pesticides and materials.Therefore,it is very necessary to develop an environmentally friendly and simple method to prepare β-amide compounds with high efficiency.Among them are three important types of derivatives:organic nitric acid esters,sulfonamides,and halogen-containing amides.Organic nitrates are important emergency drugs for cardiovascular diseases.The traditional synthetic methods of congeneric drugs require strong acid environment,expensive reagents,and toxic chemical reagents.Harsh reaction conditions limit production scale and the scope of substrates.Sulfonamide groups possess broadly biological activities and play an essential role in pesticides and medicinal chemistry.The introduction of halogen into β-amide compounds can improve the fat solubility of the drug,and affect the charge distribution and the action time of the drug molecule.In this thesis,the corresponding β-nitrate carboxamide compounds,sulfonamide compounds and halogen-containing amide compounds were synthesized by the ring-opening reaction of 2-substituted oxazolines with different nucleophiles.This method is environmentally friendly,economical and effective that it is of significance for the preparation of novel β-amide compounds.2-Amidooxazoline is a new type of oxazoline derivative that has very important applications in coordination chemistry and catalytic chemistry.In this thesis,β-carboxamide compounds can be prepared by ring opening and introducing functional groups such as halogen,-NO and bisbenzenesulfonimide.tert-butyl nitrite,bisbenzenesulfonimide and NXS(X=Br,Cl)were used as nucleophiles to carry out the ring-opening reaction of 2-substituted oxazolines,and efficiently synthesize a series of-NO,bis Benzenesulfonimide and halogenβ-carboxamide compounds and provide a feasible method for efficient screening of effective drugs.The mainly work is as following:(1)2-substituted oxazoline as the starting material,tert-butyl nitrite as the nitro donor,and the oxygen in the air as the oxidant synthesized a series of β-Nitrate Carboxamide through a nucleophilic ring-opening reaction.Through the optimization of reaction conditions,1,4-dioxane and 80 ℃ were the best solvent and temperature respectively.The reaction has the advantage of no metal participation,easily available Oxidant,simple operation,good functional group tolerance,wide ranges of substrates and cheap raw materials.It is proved by free radical interference reaction that oxygen must participate.(2)Bisbenzenesulfonimide as the nitrogen-containing nucleophile and 2-substituted oxazoline as the starting material synthesized a series of β-sulfonamide compounds with moderate to excellent yields through the nucleophilic ring-opening reaction.1,4-dioxane and60 ℃ were the best solvent and reaction temperature through the optimization of reaction conditions.This reaction has the characteristics of mild conditions,no metal participation,short reaction time,easy purification of the product,and good substrate compatibility.(3)N-bromosuccinimide(NBS)or N-chlorosuccinimide(NCS)were used as the halogenating reagent,2-substituted oxazoline as the raw material,and ammonium thiocyanate as the additive.A series of β-haloamide compounds were prepared with excellent yield through nucleophilic ring-opening reaction at room temperature.Through optimization of reaction conditions,tetrahydrofuran and acetonitrile(1:1)were the best reaction solvents.The reaction has the characteristics of mild conditions,simple operation,simple product purification,wide substrate range and high yield.In conclusion,this thesis demonstrated the synthesis of β-amido compounds containing nitro,sulfonyl or halogen through the efficient ring-opening reaction of 2-substituted amidooxazolines without metal catalysis.This type of compound contains biologically active urea structure.The corresponding products were obtained with moderate to excellent yields.The ring-opening reaction of 2-amidooxazoline has broad application prospects in pesticides,medicine and materials chemistry.