N-arylation Of Sulfoximine/Sulfonamide With Arylhydrazine Catalyzed By Copper

Sulfoximine and sulfonamide derivatives are a class of multifunctional compounds.Sulfoximine compounds can be used as various inhibitors such as clinically widely used asparagine synthetase inhibitors,clinical trials of human immunodeficiency virus type 1?HIV-1?protease inhibitors,not yet entered Both the pan-CDK inhibitor and the ATR kinase inhibitor molecular species of the market contain the structure of sulfoximine.In addition,due to the special structure of sulfoximine compounds,the sulfur atoms of some sulfoximine compounds are chiral,so these compounds can be used as novel chiral ligands in organic synthesis.Sulfonamide compounds are also widely used in many aspects such as curl-related protein inhibitors,carbonic anhydrase inhibitors for the treatment of glaucoma,and hepatitis C virus polymerase inhibitors.A number of aryl groups have been reported by the predecessors for the arylation as an aryl source,but no copper has been used as a catalyst to carry out this process.In this paper,the method of denitrifying N ₂ to realize sulfenimide/sulfonamide N-arylation was studied,and a series of N-arylation products of sulfoximine and sulfonamide derivatives were prepared.1.The authors use aryl sulfoximine and phenylhydrazine hydrochloride as reaction substrates to screen for factors involved in the reaction,such as catalysts?including various metal salts?,oxidants,solvents?including Protons and aprons?,alkalis?organic and inorganic bases?,temperature,reaction time,the authors screened the optimal reaction conditions for the realization of aryl sulfoxide as an aryl source,sulfoxide imine N-arylation reaction,at the most 21 sulfoximine N-arylation products were successfully prepared under excellent conditions.Finally,the author combines the work of predecessors and designs a series of control experiments.Through the analysis of the results,a possible reaction mechanism is pro posed.2.Under the above optimal reaction conditions,the author did not realize the N-arylation of the sulfonamides,but after simple conditional transformation,the optimal reaction conditions can be obtained.Under the optimal reaction conditions,the author also 15 sulfonamide N-aryl compounds were successfully prepared.The results show that although the N-arylation mechanism of sulfonamide and sulfoximine is similar,the conditions for achieving such as oxidant,solvent,catalyst and alkali are quite different.The authors first realized the N-arylation of sulfoximine and sulfonamide derivatives by using aryl hydrazine as the aryl source.The method has the advantages of atomic economy,few by-products,simple operation and easy separation.The prepared compounds were all confirmed by infrared spectrometer?IR?,nuclear magnetic resonance(¹H NMR and ¹³C NMR),mass spectrometry?MS?,and high resolution mass spectrometry?HRMS?.