Analysis of ring inversion of dihydrodibenzothiepines caged within a rigid framework

The ring inversion behavior of dihydrodibenzothiepine derivatives 1-S, 1-SO, and 1-SO2, containing a caged framework, was investigated using X-ray crystallography, density functional theory (DFT) calculations, and variable temperature 1H NMR spectroscopy. Variable temperature NMR measurements revealed that 1-S and 1-SO₂ undergoes a rapid and slow ring inversion, respectively, associated with respective coalescence temperatures of below 25 and ca. 45 °C. The experimental observations indicate that the activation free energy for ring inversion of 1-SO2 is larger than that of 1-S, a finding that is supported by DFT calculations. This increased energy barrier for inversion in 1-SO₂ is due to an intramolecular interaction between the O atom and H atom of the benzene ring. The intramolecular H•••O interaction, which is strongly supported by DFT calculations and X-ray crystallography, contributes to stabilization of the ground state of 1-SO₂, but must be broken in the ring inversion transition state. In contrast, 1-SO does not undergo rapid ring inversion on the NMR time scale in the temperature range of 25–130 ℃. Two factors appear to be responsible for this behavior. Specifically, the intramolecular H•••O interaction that contributes to stabilization of one conformer of 1-SO disappears in the transition state for the inversion process, and the process generating the ring-inverted conformer lacking this interaction is highly endergonic.