Condensation of 4-hydroxy-2-thiazolines with 1,2-phenylenediamine as a novel effective route to thiazolo[3,4-a]quinoxalines

Thiazolo[3,4-a]quinoxalin-4-ones were prepared in two steps starting from methyl phenylchloropyruvate using a new strategy for the construction of the ring system. A key step in this new method involves the reaction of 4-hydroxytetrahydrothiazoles with 1,2-phenylendiamines

3-(2-Chloro-5-methylphenoxy)propane-1,2-diol

3-(2-Chloro-5-methylphenoxy)propane-1,2-diol 1 is a possible precursor in the chiral beta blocker Bupranolol synthesis. Both racemic and single-enantiomeric samples of 1 were synthesized and characterized by single crystal XRD. The absolute configuration of an (S)-1 sample was determined by data refinement (the value of the Flack parameter is 0.03(4)). Hydrogen-bonded supramolecular synthons (SMS) were identified for both crystals. In rac-1, as well as in (S)-1 crystals, one of the two main SMS is the homochiral chain C11(5):21 (⋯O1–C1–C2–O2–H2⋯). The second of the two SMSs changes is the change of chiral environment. For rac-1, this is the heterochiral chain C33(9):{12/12/21}; (⋯O2–C2–C1–O1–H1⋯O′2–H′2⋯O″1–H″1⋯), in which molecules with different configurations alternate. In (S)-1 crystals, this is the homochiral chain C11(2):11 (⋯O1–H1⋯). The results obtained once again confirm the influence of the chiral environment on the crystallization of scalarly identical molecules

Intermolecular Hydrogen Bonding in Alpha-Hydroxy Carboxylic Acids Crystals: Connectivity, Synthons, Supramolecular Motifs

Synthon theory underlies the analysis and empirical prediction of the crystal structure. Supramolecular synthons (SMSs) formed by intermolecular hydrogen bonds, such as carboxylic R22(8) and C11(4) and alcoholic C11(2) ones, are among the most popular. The subject of this publication is the identification of specific synthons in alpha-hydroxycarboxylic acids (AHAs) crystals, in which carboxyl and alcohol fragments are present simultaneously. A series of 11 single-enantiomeric and racemic crystals of substituted lactic acids, the simplest chiral AHA family, were prepared and studied by the single-crystal X-ray diffraction (SC-XRD) method. Advanced analysis of our own and published (Cambridge Structural Database) data on the 33 crystal structures of lactic and achiral AHAs of diverse structures revealed that their supramolecular organization differs significantly from that of simple carboxylic acids. We found that in AHA crystals, hydrogen bonds RC(O)O−H···O(H)−C(R′R′′)C(O)OH (in our notation HB 12) and O=C(OH)C(R′R′′)−O−H···O=C(OH)R′ (HB 23) predominate. The frequency of intermolecular hydrogen bonds is interconnected with the frequency of SMSs. Thus, the synthons mentioned above occur but do not dominate in AHA crystals. Linear synthons C22(6):12/23 and cyclic synthons R22(10):23/23 and R33(11):12/23/23 are most often implemented. An essential role in the choice of cyclic synthons is played by the chiral characteristics of the sample

Intermolecular Hydrogen Bonding in Alpha-Hydroxy Carboxylic Acids Crystals: Connectivity, Synthons, Supramolecular Motifs

Synthon theory underlies the analysis and empirical prediction of the crystal structure. Supramolecular synthons (SMSs) formed by intermolecular hydrogen bonds, such as carboxylic R22(8) and C11(4) and alcoholic C11(2) ones, are among the most popular. The subject of this publication is the identification of specific synthons in alpha-hydroxycarboxylic acids (AHAs) crystals, in which carboxyl and alcohol fragments are present simultaneously. A series of 11 single-enantiomeric and racemic crystals of substituted lactic acids, the simplest chiral AHA family, were prepared and studied by the single-crystal X-ray diffraction (SC-XRD) method. Advanced analysis of our own and published (Cambridge Structural Database) data on the 33 crystal structures of lactic and achiral AHAs of diverse structures revealed that their supramolecular organization differs significantly from that of simple carboxylic acids. We found that in AHA crystals, hydrogen bonds RC(O)O−H···O(H)−C(R′R′′)C(O)OH (in our notation HB 12) and O=C(OH)C(R′R′′)−O−H···O=C(OH)R′ (HB 23) predominate. The frequency of intermolecular hydrogen bonds is interconnected with the frequency of SMSs. Thus, the synthons mentioned above occur but do not dominate in AHA crystals. Linear synthons C22(6):12/23 and cyclic synthons R22(10):23/23 and R33(11):12/23/23 are most often implemented. An essential role in the choice of cyclic synthons is played by the chiral characteristics of the sample

Chirality, Gelation Ability and Crystal Structure: Together or Apart? Alkyl Phenyl Ethers of Glycerol as Simple LMWGs

Chiral recognition plays an important role in the self-assembly of soft materials, in particular supramolecular organogels formed by low molecular weight gelators (LMWGs). Out of 14 pairs of the studied racemic and enantiopure samples of alkyl-substituted phenyl ethers of glycerol, only eight enantiopure diols form the stable gels in nonane. The formation of gels from solutions was studied by polarimetry, and their degradation with the formation of xerogels was studied by the PXRD method. The revealed crystalline characteristics of all studied xerogels corresponded to those for crystalline samples of the parent gelators. In addition to those previously investigated, crystalline samples of enantiopure para-n-alkylphenyl glycerol ethers [alkyl = pentyl (5), hexyl (6), heptyl (7), octyl (8), nonyl (9)] and racemic 3-(3,5-dimethylphenoxy)propane-1,2-diol (rac-14) have been examined by single crystal X-ray diffraction analysis. Among 22 samples of compounds 1–14 studied by SC-XRD, seven different types of supramolecular motifs are identified, of which only two are realized in crystals of supramolecular gelators. An attempt was made to relate the ability to gel formation with the characteristics of the supramolecular motif of a potential gelling agent, and the frequency of formation of the motif, required for gelation, with the chiral characteristics of the sample

Supramolecular Structure and Mechanical Performance of κ-Carrageenan–Gelatin Gel

In this work, by means of complex physicochemical methods the structural features of a composite κ-carrageenan–gelatin system were studied in comparison with initial protein gel. The correlation between the morphology of hydrogels and their mechanical properties was demonstrated through the example of changes in their rheological characteristics. The experiments carried out with PXRD, SAXS, AFM and rheology approaches gave new information on the structure and mechanical performance of κ-carrageenan–gelatin hydrogel. The combination of PXRD, SAXS and AFM results showed that the morphological structures of individual components were not observed in the composite protein–polysaccharide hydrogels. The results of the mechanical testing of initial gelatin and engineered κ-carrageenan–gelatin gel showed the substantially denser parking of polymer chains in the composite system due to a significant increase in intermolecular protein–polysaccharide contacts. Close results were indirectly followed from the SAXS estimations—the driving force for the formation of the common supramolecular structural arrangement of proteins and polysaccharides was the increase in the density of network of macromolecular chains entanglements; therefore, an increase in the energy costs was necessary to change the conformational rearrangements of the studied system. This increase in the macromolecular arrangement led to the growth of the supramolecular associate size and the growth of interchain physical bonds. This led to an increase in the composite gel plasticity, whereas the enlargement of scattering particles made the novel gel system not only more rigid, but also more fragile

Stereoselective Crystallization of Chiral 3,4-Dimethylphenyl Glycerol Ether Complicated by Plurality of Crystalline Modifications

Spontaneous resolution of Pasteur’s salt was historically the first way to obtain pure enantiomers from the racemate. The current increase in interest in the direct racemates resolution during crystallization is largely due to the opened prospects for the industrial application of this approach. The chiral 3-(3,4-dimethylphenoxy) propane-1,2-diol 1 is a synthetic precursor of practically useful amino alcohols, the enantiomers of which exhibit different biological effects. In this work, it was first discovered that racemic diol 1 is prone to spontaneous resolution. However, the crystallization process is complicated by the existence, along with the conglomerate, of two other crystalline forms. Using the differential scanning calorimetry (DSC) approach, methods have been developed to obtain individual metastable phases, and all identified modifications ((R)-1, (R+S)-1, α-rac-1, β-rac-1) were ranked by energy. The IR spectroscopy and powder X-ray diffraction (PXRD) methods demonstrated the identity of the first two forms and their proximity to the third, while β-rac-1 is significantly different from the rest. The crystal structure of the forms (R)-1 and α-rac-1 was established by the single crystal X-ray diffraction (SC-XRD) method. Preliminary information on the structure of β-rac-1 phase was obtained by the PXRD approach. Based on the information received, the experimental conditions for a successful direct resolution of racemic 1 into individual enantiomers by a preferential crystallization procedure were selected

Modulation of Molecular Structure and Mechanical Properties of κ-Carrageenan-Gelatin Hydrogel with Multi-Walled Carbon Nanotubes

Hydrogels, three-dimensional hydrophilic water-insoluble polymer networks having mechanical properties inherent for solids, have attracted continuous research attention over a long time period. Here, we studied the structure and properties of hydrogel based on gelatin, κ-carrageenan and CNTs using the combination of SAXS, PXRD, AFM microscopy, SEM and rheology methods. We have shown that the integration of polysaccharide and protein in the composite hydrogel leads to suppression of their individual structural features and homogenization of two macromolecular components into a single structural formation. According to obtained SAXS results, we observed the supramolecular complex, which includes both polysaccharide and protein components associated with each other. It was determined that hydrogel structure formed in the initial solution state (dispersion) retains hydrogel supramolecular structure under its cooling up to gel state. The sizes of dense cores of these polyelectrolyte complexes (PEC) slightly decrease in the gel state in comparison with PEC water dispersion. The introduction of CNTs to hydrogel does not principally change the type of supramolecular structure and common structural tendencies observed for dispersion and gel states of the system. It was shown that carbon nanotubes embedded in hydrogel act as the supplementary template for formation of the three-dimensional net, giving additional mechanical strengthening to the studied system