Tetrahydrothiophene and Tetrahydrofuran, Computational and X-ray Studies in the Crystalline Phase

Abstract

Calculations at various levels of theory with different methods and respective evaluations confirm that the twist conformation (C2) is preferred for tetrahydrothiophene (THT) in the gas phase. In the crystalline phase, achieved by a laser assisted crystallization device, THT has C1 symmetry (slightly distorted C2 symmetry) in the chiral space group P212121. This is obviously a packing effect caused by the nonsymmetrical arrangement of neighboring molecules. The distortion from C2 symmetry costs very little energy as confirmed by computational methods in the gas phase. Only one enantiomer of the chiral THT is found in the cell which requires spontaneous crystallization, which results in a racemic mixture of crystals, or a racemization occurs prior to/during nucleation or in the “embryonic” state. The racemization happens by a mechanism that can be described as a partial pseudo rotation within a five-membered mono-heterocycle with a C2–CS–C2′ transition (C2 and C2′ are enantiomers) maintaining the heteroatom residing within the symmetry elements. While THT has the molecular symmetry of the gas phase almost also in the crystalline phase, THF has an envelope conformation (CS). This was also established by calculations at various levels of theory which agrees well with the previously experimentally found conformation by electron diffraction. However, in the X-ray crystal structure, previously determined by Luger & Buschmann, THF has C2 symmetry in the centrosymmetric space group C2/c with the oxygen atom situated on the crystallographic C2 polar axis, requesting a racemic crystal for the twisted conformers of the enantiomers. No solid-state phase transitions were detected within the experimental ranges for THT and THF. Following the stabilization by molecular clustering, and ending at the crystal lattice, we stepwise increased the number of molecules by calculation of the respective monomers, dimers, trimers, and tetramers for THF and THT. The starting point was taken from the arrangements as found in the respective crystal structures. Both conformational enantiomers are equal in energy. In such cases, a crystal may contain either a racemate of conformers or one of the conformational enantiomers only. The first case is observed in THF, the latter one in THT. It is quite likely that the selection of one enantiomeric conformer of THT from an equilibrium of conformers at the early stage of nucleation (“embryonic” stage) is responsible for the spontaneous crystallization. In order to check if THF could form a polymorph with the molecular packing of THT and vice versa, we first calculated THF and THT in their respective crystal lattices as determined by X-ray diffraction. Exchanging the compounds in the THT and THF crystal lattices (i.e., replacing O against S and vice versa) results in significantly worse lattice energies indicating that such a polymorph is not a probable option.