A density functional theory study of the hydride shift in the Eschweiler–Clarke reaction

Abstract

The Eschweiler-Clarke (the amine methylation) reaction was investigated by density functional theory (DFT) calculations. First, a reaction model of4 was employed for geometry optimizations. Geometries and activation free energies of transition states (TSs) by eight DFTs, B2PLYP-D3, B3LYP, B3LYP-D, BP86-D, PBE0-D, M06-2X, wB97X-D, and APF-D, along with MP2 were compared. Four elementary processes were obtained. The ratedetermining step is of the hydride-transfer TS, H 3 C N + H CH 2 + HCO 2 À ! H 3 C NH CH 3 + CO 2 . Whereas BP86-D and APF-D gave underestimated energies, M06-2X was found to be a reasonable DFT to trace the present reaction. Second, by the use of M06-2X/6-311++G**, hydride-shift TSs were examined for various sizes of the water cluster (H 2 O) n , and the controversial two mechanisms were evaluated. It was suggested that the first formic acid contributes to formation of the iminium ion H 3 C N + H CH 2 and the second formic acid works for the hydride transfer. The Eschweiler-Clarke reaction was described by the scheme, R