Synthesis, NMR Spectroscopy and Molecular Modelling of the 2-Methyl-2,3,4,5-tetrahydro-1<i>H</i>-[1]benzothieno[2,3-<i>c</i>]azepine
A new approach to the preparation of condensed azepines was demonstrated with a case study of the 2-methyl-2,3,4,5-tetrahydro-1 H -[1]benzothieno[2,3- c ]azepine synthesis. The key stage of the synthesis protocol is the formation of an azepine ring under the Eschweiler-Clark reaction conditions. The Gibbs energy of activation for the inversion of azepine ring was determined by dynamic NMR <sup>1</sup>H spectroscopy. Molecular modeling of the structure and evaluation of chemical shifts of <sup>1</sup>H and <sup>13</sup>C nuclei were performed for the 2-methyl-2,3,4,5-tetrahydro-1 H -[1]benzothieno[2,3- c ]azepine. The calculation of the magnetic shielding constants was performed 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 chemical shifts of the <sup>1</sup>H and <sup>13</sup>C nuclei for 2-methyl-2,3,4,5-tetrahydro-1 H -[1]benzothieno[2,3- c ]azepine are in good agreement with the experimental ones obtained from DMSO- d <sub>6</sub> solution.