Studies On The Acid/Halide Cooperative Catalyzed Activation And Transformation Of Unactivated Amides And Esters

Amides and esters are common carboxylic acid derivatives.They exist widely in various natural and synthetic molecules.Due to the strong resonance effect,amides and esters are very stable to participate in reactions under mild reaction conditions.Thus,studies on the activation and functionalization are of significance in sicence and economy.In this paper,we focused on developing new methods for the activation and transformation of unactivated amides and esters under metal-free reaction conditions.The specific contents come as follows:(1)The transamidation of unreactive amides through acid/iodide cooperative catalysis.Amide N-C(O)bond was activated in-situ by acid/iodide to generate active acyl iodide,followed by coupling with equivalent amine,thus achieving the transamidation of unactivated amides.This reaction showed wide substrate and high chemo-selectivity.A variety of aromatic and aliphatic N,N-dimethyl amides could react with aliphatic,heterocyclic and even weakly nucleophilic aromatic amines to produce the corresponding new amides in high yields.Various functional groups such as methoxy,trifluoromethyl,cyanide,ester and carboxyl all could be compatible in the present catalytic system.In addition,this reaction was applicable to the synthesis of clinic drugs such as paracetamol,fenfuram,gallic acid derivatives,and tamibarotene.Those results well demonstrated the synthetic value of this new reaction in organic synthesis.This reaction not only provides a solution to the long-standing challenge in activation of unactivated amides,but also expands the application of amides in organic synthesis.(2)The transesterification of unreactive methyl carboxylate through acid/halide cooperative catalysis.Methyl carboxylate was activated by acid/halide to generate active acyl halide,followed by coupling with phenol or alcohol to produce the expected esters in high yields.High functional group tolerance was demonstrated,various valuable function groups such as methyl,phenyl,trifluoromethoxy and nitro all were well tolerated under the current reaction conditions.This reaction was also applicable to modify the derivatives of drugs such as gallic acid trimethyl ether,trans-cinnamic acid,ibuprofen and probenecid.Those results showed the potential synthetic value of this reaction in organic synthesis.