How does the conformational landscape change on replacement in tetralin? A computational investigation with oxygen, sulfur, and selenium

Context

The oxygen, sulfur, and selenium derivatives of tetralin termed as isochroman (IC), isothiochroman (ITC), and isoselenochroman (ISC) showed interesting conformational patterns. In particular, ITC and IC have immense pharmacological significance. The twisted conformer is the global minimum in IC, where the bent is a transition state (TS) and remains 1100 ± 100 cm⁻¹ higher. The bent form in ITC and ISC possesses the lowest energy. But, the twisted conformer lies higher by about 80 ± 20 cm⁻¹ in ITC and 700 ± 50 cm⁻¹ in ISC. The potential energy surfaces (PES) locate all the conformations and TSs. Molecular electrostatic potentials indicate the sites of electrophilic interactions, and the small energy difference between the minima in ITC predicts an interesting interplay of intermolecular interactions in suitable environments. The validity of the maximum hardness principle and minimum electrophilicity principles is checked. Frontier molecular orbitals show the change in electron densities on excitation, which are mostly π → π^* in nature. Hyperconjugative interactions involving different σ and lone pair orbitals explain the change in conformational patterns in these molecules. We suggest some experiments to corroborate our findings.

Methods

Computations are performed with different functionals (B3LYP, M06-2X, and ωB97X-D) in DFT as well as ab initio methods (MP2 and CCSD) with 6-311G +  + (2d, 3p) and augmented cc-pVDZ as basis sets. Gaussian 09 is used for the above computations. PED analyses were performed by Veda 4 software. For viewing and plotting purposes, Gaussview 5.0 and Origin 8.5 are used.