Development Of New Periodic Nitrate Reagents And Their Application In Green And Efficient Nitrate Synthesi

Organic nitrates are widely used in medicine,materials,organic synthesis and environmental chemistry.They are compound with important application value.The traditional synthesis method relies on the nitration of alcohol by the mixed acid system of concentrated nitric acid and sulfuric acid,with poor selectivity and low functional group tolerance,which also causes serious resource waste and high energy consumption due to empoying a large amount of water dilution,alkali-washing,water-washing and other operations.The prior synthesis methods of nitrate generally have the problems of narrow application range of substrate,low safety,cumbersome post-treatment process,serious material waste and poor selectivity.In order to solve this problem and avoid the use of mixed acids or metal nitrates,this paper developed a new method of green,efficient and fast synthesis of hypervalent iodide nitrooxylating reagents and conducted a series of studies on its reactivity.The specific work is as follows:（1）Aryliodine diacetate and aryliodine dicholoride were respectively used to synthesize a series of acyclic hypervalent iodide nitrooxylating reagent with diverse structure and adjustable activity.The two methods have their own advantages and complement each other,and the operation is simple,the conditions are mild,green,safe,fast and efficient,and the synthesis of hypervalent iodide nitrooxylating reagents can be achieved at 100-gram-scale.The studies of physical and chemical properties such as solubility,thermal stability and sensitivity test indicated that the reactivity of acyclic hypervalent iodide nitrooxylating reagent was higher than that of cyclic hypervalent iodide reagent,and most acyclic hypervalent iodide reagents had high stability and did not decompose after two years of storage at room temperature.（2）On the basis of the synthesis of hypervalent iodide nitrooxylating reagents,a green,efficient and fast synthesis method ofβ-halogenated nitrates was developed.With hypervalent iodide reagent as nitrate source and halotrimethylsilane as halogenatung source,the precise halogen-nitrooxylation reaction of alkyl olefin with high regioselectivity and high yield was achieved by using only 0.5 mol%Fe Cl₃ in air atmosphere.High regioselectivity halogen-nitrooxylation of aryl alkenes can also be achieved without catalyst.The protocol is synthesis of nitrate esters with the properties of broad spectrum,mild conditions,simple operation,wide range of substrates and strong functional group tolerance.This method can be used to synthesize nitrate derivatives of Aspirin,Ibuprofen,Probenecid,Steroids,Sugars,Nucleosides,Amino acids,Peptides and other drug molecules and natural products.It noted that using this method,ethylene can be used as material to prepare 2-iodoethyl nitrate in 10-gram-scale.As an efficiency synth,2-iodoethyl nitrate can realize nucleophilic substitution reactions of O-H,N-H and S-H bonds,and a series of more significant substituted ethyl nitrate can be obtained.（3）A green protocol for preparingβ-nitrate ketone was developed.In this protocol,cyclopropanol silyl ether was synthesized by ring-opening nitrooxylation using hypervalent iodide nitrooxylating reagent as nitrate source and 5 mol%Zn（OTf）₂ as catalyst in air at room temperature.The reaction is a green,efficient and quick method for preparingβ-nitrate ketone with simple operation,wide application range of substrate and high functional group tolerance.Controlled experiments and DFT calculations demonstrated that the reaction is triggered by the complexation of oxygen atoms in silyl ether substrate with zinc,then exchange with oxygen atoms in I-O-I of the reagent,and finally esterification with ring-opening nitrate and release of iodobenzene.