Mechanism Study On Transamidation Reaction Catalyzed By Boric Acid

Density functional theory of M062X/6-31++G(d,p)is used to study the reaction mechanisms in transamidation of carboxamide with aniline catalyzed by boric acid.Two possible reaction mechanisms,Path I and Path II,are proposed.In the two mechanisms,the boric acid activates the carbonyl oxygen of the substrate acetamide through the formation of B-O bond,and the hydrogen bonding between the hydroxyl oxygen of boric acid and the amino hydrogen of the carboxamide also contributes to the activation of the amide.In Path I,the nucleophilic attack of aniline to the carbonyl carbon atom is coupled with the hydrogen transfer from amino of aniline to the substrate for the release of ammonia.While in Path II,the nucleophilic attack of aniline corresponds to its hydrogen transfer to the boric acid for the formation of a water.Subsequently,the formed water attacks the boric atom,with hydrogen shift to the amino of acetamide,and the product amide is generated.For the two possible mechanisms,direct transamidation and water assisted transamidation are included.The solvent effect of toluene and water is simulated by SMD(Solvation Model Density).Our theoretical results showed that Path II without water participation is the favorable pathway with Gibbs free energy barrier of 28.2 kcal/mol compared to that of 33.0 kcal/mol for Path II with one water participation.While the Gibbs free energy barriers of Path I without water,with one or two water are 47.0 kcal/mol,32.9 kcal/mol and 36.2 kcal/mol respectively.In addition,the transamidations of primary,secondary and tertiary carboxamides with benzylamine are also investigated,and the calculated Gibbs free energy barriers are 23.9 kcal/mol,27.5 kcal/mol and 30.9 kcal/mol,respectively.Our theoretical study coincides well with the experimental result,and would be useful for further understanding and future experimental investigation on such transamidation reaction.