Search

New racemic and enantiopure N-phosphorylated thioureas bearing 1-phenylethyl or tetrahydronaphthalenyl fragments were synthesized. According to NMR data assisted by DFT calculations, the preferred conformation is stabilized by an intramolecular hydrogen bond. This form in solution is in equilibrium with dimeric N–H···S hydrogen-bonded associates, the population depending on the concentration. In the crystalline phase the low-energy conformation with an intramolecular H-bond is realized only in the racemic tetrahydronaphthalenyl derivative. In most crystals various types of intermolecular hydrogen bonding are observed, accompanied by the formation of infinite linear chains or helical structures. Due to the conformational lability of compounds and competitive intermolecular H-bonding, multiple polymorphic modifications are formed. Therefore, crystallization of enantiopure 1-phenylethyl derivatives from various solvents results in concomitant polymorphs at room temperature. One of them undergoes reversible two-step phase transitions from the high-symmetry I41 space group (Z′ = 1, no disorder) via the P41 space group (Z′ = 6) to the monoclinic P21 space group (Z′ = 16) accompanied by drastic concerted conformational changes. Notably, the optimization of the crystal packing is observed upon phase transitions with a gradual reduction of the void space in the unit cell from 4.5% to 0.8%. This is a rare case of several high-Z′ polymorphs for one compound, with chirality playing an important role.

Asymmetric dihydroxylation of mono nitrophenyl allyl ethers leads to the corresponding non-racemic 3-(nitrophenoxy)-propane-1,2-diols 1a – c . As this takes place, regardless of the reagent used (AD-mix-α or AD-mix-β), the configuration of the predominant enantiomer for the para - and meta -nitrosubstituted products is opposite to the configuration of the ortho -nitrophenyl derivative. A correlation between the melting points and vibrational spectra of the racemic and enantiopure diols 1a – c allowed us to establish that all of the chiral substances investigated formed stable racemic compounds in the solid phase.

A series of enantiopure and racemic p -alkylphenyl glycerol ethers 1a – k were synthesized. A new, sensitive, and pictorial method of comparison of the IR spectra of solid enantiopure and racemic samples was developed to obtain preliminary information on the crystallization types of these compounds. In order to detect the subtle differences in the organization of the chiral solid phase, a new easily implemented approach, based on a chromatographic measuring of the relative abundance of the enantiomers in a single solution in equilibrium with a solid sample of arbitrary (0 n -Pr) and one borderline case (Alk = n -Bu) are disclosed. Higher members of the series of 1 (starting with an n -Bu derivative) are turned into liquid crystals upon melting; no significant differences between racemic and non-racemic samples were found. Only enantiopure methyl-, n -butyl, n -pentyl, n -hexyl, and n -heptyl substituted 1 were able to form supramolecular gels in hydrocarbon solvents; all racemic ethers 1 did not show such ability.

Popular chiral drugs, guaifenesin, methocarbamol, and mephenesin were investigated by single-crystal X-ray analysis both for enantiopure and racemic samples. The absolute configurations for all substances were established through Flack parameter method. The conglomerate-forming nature for the compounds was confirmed by equivalence of crystal characteristics of enantiopure and racemic samples. The molecular structures and crystal packing details were evaluated and compared with one another for all three investigated substances.

The muscle relaxant methocarbamol 2 and tranquilizer mephenoxalone 3, as well as intermediate cyclic carbonate 4, have been prepared in enantiopure form by starting from enantiopure guaifenesin 1 easily available by an entrainment resolution procedure. Thermal investigations reveal that 2 is probably a conglomerate forming substance, 3 forms a stable racemic compound, and 4 occupies an intermediate position. The enantiomeric excess of a binary phase eutectic point for these substances comprises 0%, 85%, and 10%, respectively.