Study On The Selective Coupling Reactions Of N-methoxy Arylformamide

Amide bond is the basis of life,whether DNA,RNA,protein,there are a large number of amide bonds.Therefore,the construction of amide bond plays an important role in synthetic chemistry.Amide compounds contain two nucleophilic sites,nitrogen and oxygen.How to selectively realize C-N/O coupling is still a major challenge in amide chemistry.Recently,N-methoxy arylformamides,as a new class of synthons,have been widely used in the diversity construction of amide bond containing compounds.In this paper,based on the nitrogen and oxygen active sites of N-methoxy arylformamides,the selective C-N,C-O,and P-O coupling reactions of N-methoxy arylformamides were through the design of different reaction processes,and a series of N-aryl formamide,aryl-N-methoxy arylimide ester and phosphonic acid-arylimide anhydride were synthesized.This is the main introduction of this paper:1.C-N coupling reaction of N-methoxy arylformamide and arylboric acid catalyzed by iron saltA C-N coupling reaction of N-methoxy arylformamide with arylboronic acid catalyzed by iron salts was developed.In this section,the types of catalysts,suitable temperature range,solvent selection and other reaction conditions were systematically explored,and the optimal parameters were obtained:Fe Cl₃ was selected as the catalyst,and the dosage was 20 mol%;DCE was selected as the analytical reagent;the reaction temperature was 120℃.N-methoxy arylformamide and arylboric acid were stirred in the reaction pot for 24 h,and the C-N coupling product N-aryl formamide was successfully obtained.The coupling reaction used cheap iron salt as catalyst and did not need to add alkali,which met the development requirements of green chemistry.2.C-O coupling reaction of N-methoxy arylformamide and arylboric acid catalyzed by copper saltA C-O coupling reaction of N-methoxy arylformamide with arylboronic acid catalyzed by copper salt was developed.In this section,the reaction conditions such as the type of catalyst,the applicable temperature range,and the selection of solvent were systematically explored,and the optimal parameters were obtained:Cu I was used as the catalyst,and the dosage was 20 mol%;Na₃PO₄·12H₂O was selected as alkaline additive;DCE was selected as the analytical reagent;the reaction temperature was 130℃.N-methoxy arylformamide and arylboric acid were stirred in the reaction pot for 24 h,and the C-O coupling product aryl-N-methoxy arylimide ester was successfully obtained.3.P-O coupling reaction of N-methoxy arylformamide and phosphite catalyzed by copper saltA P-O coupling reaction of N-methoxy arylformamide with phosphite catalyzed by copper salt was developed.In this section,the reaction conditions such as the type of catalyst,the applicable temperature range,and the selection of solvent were systematically explored,and the optimal parameters were obtained:Cu（OAc）₂·H₂O was selected as the catalyst,and the dosage was 20 mol%;Na HCO₃ was selected as the alkaline additive;toluene was selected as the analytical reagent;the reaction temperature was 60℃.N-methoxy arylformamide and phosphite were stirred in the reaction pot for 12 h,and the P-O coupling product phosphonic acid-arylimide anhydride was successfully obtained.