A DFT Study On Formation Of Bisaryloxime Ether From Benzaldehyde And Phenoxyamine

The reaction mechanism between benzaldehyde and phenoxyamine to produce bisaryloxime was studied using Density Functional Theory (DFT) in gas phase in order to discuss the reason why tran-bisaryloxime is the main product.Oxime Ethers are important compound due to their potential application in bioorganic and medicinal chemisity. All of calculations were performed at the B3LYP/6-31++G** level using Gaussian 03 software package. The transition states were confirmed by only one imaginary frequency. The three path are found: (1) In the neutral mechanism, phenoxyamine directly reacts with benzaldehyde to produce the product passing an intermediate (INT) and two TSs (TS1 and TS2). The first step from reactant (R) to intermediate (INT) is a hydrogen transfer process through TS1_RB. Then INT produces the final product through TS2 in the second step. The higher energy barrier of the second step than the first step indicats that the second step is the rate-determining step. Meanwhile, the barrier to form EB is lower than ZB. Therefore, the reaction favored to produce EB. (2) In direct acid-catalyzed mechanism, acetic acid interacts with the benzaldehyde at first, then the protonated benzaldehyde is attacked by phenoxyamine, and the protoned product forms via an intermediate (INT1) and a TS (TSH) accompanied by the elimination of water. (3) In water-assisted acid-catalyzed mechanism, the protonated products are reached via TSW accompanied by two water molecules. Compared with the three mechanisms, the barrier height of neutral mechanism is higher than the two acid-catalyzed mechanisms. So the two acid-catalyzed mechanisms are more favorable than neutral mechanism. In water-assisted acid-catalyzed mechanism, the barrier height is much lower due to forming a six-membered ring. Therefore the water-assisted acid-catalyzed mechanism is more favorable than the former two mechanisms. Meanwhile, the barrier to produce EB is a little lower than that of ZB. Therefore, EB is the more favorable in thermodynamics.In order to explore why EB formation is the main product of reaction, chemical hardness, chemical potential and structure parameter of EB/ZB is analyzed at the B3LYP/6-31++G** level. The calculated NBO results shown that the localized energy of EB is lower than that of ZB while the delocalized energy of EB is higher than that of ZB. This indicates the stability difference between EB and ZB might be not only related to thermodynamics factor but also likely related to the role ofπstacking between phenyl groups and hydrogen bonds between N atom and phenyloxy oxygen atom.