Methodology Research On The N-Methylation/Aryloxymethylation Of Arylsulfonamides

Sulfonamide compounds are rich in variety and involve a wide range of f ields.Its basic structure R-S(=O)₂-N contains nitrogen atoms and can be used as nitrogen-containing nucleophiles to construct(sp³)C-N bonds and synthesize various nitrogen-containing compounds.It is reported that there are C-N bonds in pharmaceutical intermediates,pesticide reagents and natural products with biological activities,so sulfonamide compounds naturally have unique activities such as antibacterial,antifungal,antiviral,weeding and disinfestation,etc.,which are mainly involved in the fields of biomedicine,functional materials and agricultural production in current applications.In the field of organic synthesis,the research on the synthesis methods of sulfonamide compounds has always attracted much attention.Transition metal catalyzed coupling reaction is one of the efficient synthesis methods.The transition metal catalyst can greatly reduce the activation energy required for the reaction,so the reaction can take place without high temperature and high pressure,and it has the characteristics of high selectivity,atom economy and environmental friendliness.At present,it is widely used in the construction of various chemical bonds such as N-C,N-X bonds,and among many transition metals,copper metal catalyst has the advantages of low cost,low toxicity,environmental protection and the like and is widely used.In the past,commonly used metal alkanes,halogenated hydrocarbons,halogenated unsaturated hydrocarbons and alcohol compounds are coupled with nucleophilic reagents with N-H groups under the catalysis of transition metals to realize N-H functionalization,which is relatively harsh in conditions and low in substrate universality.In view of the above reasons,based on the past research in the laboratory,this paper explores the N-H functionalization of two sulfonamide compounds and constructs(sp³)C-N bonds.The main contents are as follows.2.In this paper,the author uses sulfonamide and dicumyl peroxide(DCP)as raw materials.Under the catalysis of copper diacetylpyruvate,DCP is split evenly to generate methyl radicals,which undergo oxidative coupling reaction to generate N-methylsulfonamide compounds.The reaction is simple and easy to implement,and has the advantages of high efficiency,environmental protection and good s ubstrate universality.The reaction efficiencies of different sulfonamides in this reaction were comprehensively compared,and a total of 23 N-methylated products were obtained.All the target products were characterized by nuclear magnetic resonance(NMR),mass spectrometry(MS),infrared(IR)and other methods.Finally,the radical mechanism of the reaction was explored and the possible reaction course was deduced.2.In this paper,the author uses(quinolone-8-yl)arylsulfonamide compounds and 1,4-dimethoxybenzene as raw materials,under the catalysis of copper acetate,TBHP as oxidant and K₂HPO₄ as additive,and reacts in acetone solvent at 120 ^oC for12 hours to generate a new type of N-aryloxymethylated sulfonamide compound.The reaction selectivity is highly specific.The reaction efficiency of different sulfonamide compounds in this reaction is compared,and a total of 9 target products are obtained.All target products are characterized by nuclear magnetic resonance(NMR),mass spectrometry(MS),infrared(IR)and other methods.