Synthesis, NMR Spectroscopy, and Molecular Modeling of 2-Methyl-2,3,4,5-tetrahydro-1H-[1]benzothieno[2,3-c]azepine

A new synthetic approach to fused azepines was demonstrated on an example of the synthesis of 2-methyl-2,3,4,5-tetrahydro-H-1-[1]benzothieno[2,3-c]azepine. The key stage of the synthesis is the formation of the azepine ring under the Eschweiler-Clark reaction conditions. The Gibbs energy of activation for the inversion of the azepine ring was determined by dynamic H-1 NMR spectroscopy. Molecular modeling of the structure and estimation of the H-1 and C-13 NMR chemical shifts were performed for 2-methyl-2,3,4,5-tetrahydro-1H-[1]benzothieno[2,3-c]azepine. The magnetic shielding tensors were calculated by the standard GIAO method using the B3LYP/6-31G(d,p)-optimized molecular geometry parameters. The solvent effect was taken into account in the PCM approximation. The calculated H-1 and C-13 NMR chemical shifts of 2-methyl-2,3,4,5-tetrahydro-1H-[1]benzothieno[2,3-c]azepine are in good agreement with the experimental values observed in the spectra of its DMSO-d(6) solution.