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A density functional theory study of the hydride shift in the Eschweiler–Clarke reaction
Author(s) -
Yamabe Shinichi,
Tsuchida Noriko,
Yamazaki Shoko
Publication year - 2021
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.4253
Subject(s) - chemistry , hydride , formic acid , density functional theory , iminium , thermochemistry , amine gas treating , medicinal chemistry , ion , computational chemistry , hydrogen , organic chemistry
The Eschweiler–Clarke (the amine methylation) reaction was investigated by density functional theory (DFT) calculations. First, a reaction model of H 3 CNH 2 + HC(O)OH + CH 2 O + (H 2 O) 3 → (H 3 C) 2 NH + CO 2 + (H 2 O) 4 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 rate‐determining step is of the hydride‐transfer TS, H 3 CN + HCH 2 + HCO 2 − → H 3 CNHCH 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 CN + HCH 2 and the second formic acid works for the hydride transfer. The Eschweiler–Clarke reaction was described by the scheme, R 1 R 2 NH + H 2 CO + (HCOOH) 2 + (H 2 O) n → R 1 R 2 NCH 3 + CO 2 + HCO 2 − + H 3 O + (H 2 O) n .