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

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.