Difunctionalization Of Unsaturated Bonds And Aromatic Nitration Based On NO₂⁺

Nitro compounds are widely used in all aspects of social life such as medicine,printing and dyeing,perfume,blasting,because of their unique structural characteristics,biological and physiological activities,and physical and chemical properties.Since the discovery of the mixed acid nitration reaction of benzene compounds in the 18th century,the development of the nitration reaction had make good achievements from the electrophilic nitration of NO₂⁺to the nitration of free radicals with the participation of·NO₂.Nevertheless,the nitration reaction was still limited to the nitration of aromatics and the synthesis of nitroolefins.And,the related efficient examples were also lack of large-scale synthesis applications,which have serious drawbacks including complex operation and narrow substrate scope due to the high toxicities of reagent,expensive reaction cost,harsh reaction conditions,the risks of safety and serious pollution.In particular,the·NO₂ type nitration method also has fatal shortcomings such as difficult amplification of reaction and hard controllable process.The structural units are extremely important which containing chloro and nitro groups as high-value synthetic building blocks and drug precursors.At the same time,difunctionalization of alkenes is an efficient and powerful strategy for incorporation of two vicinal functional groups into readily available alkenes in a single step via the addition of a C=C double bond.Therefore,it is necessary to directly use cheap nitrate as the starting materials to develop a cheap,green,and efficient catalytic chloronitration method based on NO₂⁺.In view of the defects and challenges of the nitration reaction,a novel and practical chloronitration of alkenes in the presence of easily available TMSCl and guanidine nitrate has been developed by using cheap copper sulfate pentahydrate as the catalyst.The reaction method not only has mild reaction conditions,cheap and available materials;but also has a wide range of substrates,which can be used for various electron-rich olefins,electron-deficient olefins,multi-substituted olefins,allylamines,allyl esters and alkynes.A variety of vic-chloronitro compounds were directly synthesized in good to excellent yields on up to 100 mmol scale under mild reaction conditions.The reaction products can not only eliminate HCl to give nitroalkenes through one-pot via base,but also can be used as a synthetic building block for Friedel-Crafts arylation,nucleophilic substitution amination,nucleophilic substitution thioetherification,Grignard reaction,and Click reaction with NaN₃,to give diverse nitro compounds bearing a vicinal nucleophilic“C”,“N”or“S”unit in high yield.The protocol shows the excellent potentiality in the filed of organic synthesis and complex molecular modification.At the same time,this method can also be extended to the nitration of electron-rich aromatics,which can selectively realize the mono-nitro or dinitro electrophilic substitution of numerous phenols,phenyl ethers,and benzamide compounds.It is worth mentioning that both the chloronitration and the electrophilic substitution reaction of the aromatic ring have been successfully scaled up to the 20 gram level under laboratory conditions.We believe that our method has a brilliant potentiality for industrial application.Mechanism studies have shown that in this methodology,Me₃SiONO₂ was generated in situ by Me₃SiCl and guanidine nitrate as the active intermediate of the reaction,and Raman spectroscopy provides direct evidence for the presence of NO₂⁺in the reaction system.Combined with the control experiments,we speculate that the specificity of the chloronitration reaction may be caused by the NO₂⁺Cl^-ion pair.The trans-addition type of nitro-and chloro-groups are revealed by the NOESY spectrum.Finally,we give a simple and reasonable reaction process for the chloronitration of olefins.