4‑Benzoylamino-3-hydroxybutyric Acid, Historically First “Anomalous Racemate”: Reinvestigation

Chiral 4-benzoylamino-3-hydroxybutyric acid (<b>1</b>) was recognized in 1930 as the first example of “anomalous racemates” (correct to say, anomalous conglomerates), that is, specific addition compounds formed by different enantiomers in unequal ratio. Through the comparative (racemic against homochiral samples) inspection of the IR spectra, single crystal X-ray diffraction, PXRD analysis, and solubility data we have found that this substance forms normal racemic compound in the solid state, and must be excluded from the very short list of anomalous conglomerates. At the same time <i>homo</i>-<b>1</b> is dissolved in 25 times better than <i>rac</i>-<b>1</b>, and this feature belongs to another interesting and rare type, namely, “anticonglomerates”. Some of the reasons for this behavior are discussed

4‑Benzoylamino-3-hydroxybutyric Acid, Historically First “Anomalous Racemate”: Reinvestigation

Chiral 4-benzoylamino-3-hydroxybutyric acid (<b>1</b>) was recognized in 1930 as the first example of “anomalous racemates” (correct to say, anomalous conglomerates), that is, specific addition compounds formed by different enantiomers in unequal ratio. Through the comparative (racemic against homochiral samples) inspection of the IR spectra, single crystal X-ray diffraction, PXRD analysis, and solubility data we have found that this substance forms normal racemic compound in the solid state, and must be excluded from the very short list of anomalous conglomerates. At the same time <i>homo</i>-<b>1</b> is dissolved in 25 times better than <i>rac</i>-<b>1</b>, and this feature belongs to another interesting and rare type, namely, “anticonglomerates”. Some of the reasons for this behavior are discussed

Unusually High Efficiency of β‑Cyclodextrin Clathrate Preparation by Water-Free Solid-Phase Guest Exchange

An effective preparation procedure is offered for β-cyclodextrin (bCD) clathrates with volatile guests of moderate hydrophilicity, which otherwise require a finely tuned optimization of the bCD/water/guest ratio. The proposed procedure includes guest exchange in a water-free bCD matrix. As a result, more stable clathrates with a higher inclusion capacity can be prepared than by direct saturation of dried or hydrated bCD. To find an optimal preparation method, the structure–property relationships were studied for four different ways of bCD clathrate formation with guests of varying molecular structure. The study was much simplified by used procedures excluding direct contact of guest and water liquids with bCD. Besides, in clathrate preparation experiments, the thermodynamic activities of water and guest were varied independently, which makes explicit the role of water in this process. Hydration of bCD reduces its inclusion threshold for hydrophobic guests by their activity (relative vapor pressure), giving favorable hydration effect for their inclusion. Besides, water competes with hydrophilic guests for binding sites in bCD at high water activities. Together with bCD dehydration by excess of hydrophilic guests, these observations give a complete thermodynamic picture, which may be fruitful for elaboration of guest encapsulation techniques by cyclodextrins

Crystallization Features of the Chiral Drug Timolol Precursor: The Rare Case of Conglomerate with Partial Solid Solutions

A synthetic precursor of the chiral drug timolol, 4-[4-(oxiran-2-ylmethoxy)-1,2,5-thiadiazol-3-yl]-morpholine (<b>2</b>) represents a rare case of conglomerate with partial solid solution. This fact was established by inspection of an original solubility test, by the originally developed IR spectra analysis, and by construction of a binary phase diagram which is totally based on thermochemical measurements. The special procedure was developed for quantitative analysis of complex differential scanning calorimetry traces for incongruently melting samples of intermediate enantiomeric composition. The X-ray analyses were performed on a single crystal of <b>2</b> grown from the enantiopure feed material and on a single crystal picked out from the racemic polycrystalline sample. The structure of the enantiopure crystal was solved and refined in the <i>P</i>2₁2₁2₁ space group with the only symmetry independent molecule in the unit cell. The structure of the crystal picked out from the racemic <b>2</b> sample was solved and refined in the <i>P</i>1 space group with four symmetry independent molecules in the unit cell. The epoxy moieties of the independent molecules in this crystal were found to be disordered over two positions with almost equal relative occupancies of opposite enantiomers for all the molecules. The quantitative characteristics of the disorder, 0.78(0.02):0.22(0.02), are close to those found by an independent method of the Tammann diagram

Spontaneous Resolution of Chiral 3‑(2,3-Dimethylphenoxy)propane-1,2-diol under the Circumstances of an Unusual Diversity of Racemic Crystalline Modifications

Depending on the conditions of crystallization from solutions, racemic 3-(2,3-dimethylphenoxy)­propane-1,2-diol <b>1</b> forms three relatively stable crystalline modifications. Each of the crystalline forms, namely, two polymorphic racemic compounds and a racemic conglomerate, has been characterized by single-crystal X-ray diffraction. Two more metastable racemic compounds crystallized from the racemic melt have been found by differential scanning calorimetry method. Additional thermochemical investigations allowed to plot the dependence of the free Gibbs energy on temperature for all the phases found. With the help of slurrying experiments, the nature of the transitions between solid phases has been specified. It has been found that even a slight predominance of one of the enantiomers in almost racemic <b>1</b> samples ensures the crystallization of the conglomerate. The revealed features of <i>rac</i>-<b>1</b> crystallization have been taken into account during the realization of its resolution into individual enantiomers by the entrainment procedure

The interaction of 2-(5-methyl-2-phenyl-2h-1,2,3-diazaphosphol-4-yl)-4h-benzo[<i>e</i>]-1,3,2-dioxaphosphinin-4-one with activated carbonyl compounds. Synthesis of bis-heterocyclic systems containing di- and tetracoordinated phosphorus

<p>The interaction of 2-(5-methyl-2-phenyl-2<i>H</i>-1,2,3-diazaphosphol-4-yl)-4<i>H</i>-benzo[<i>e</i>]-1,3,2-dioxaphosphinin-4-one with mesoxalic and trifluoropyruvic acids ethyl and diethyl esters, hexafluoroacetone and chloral proceeds with an exclusive participation of P(III) atom and allows to obtain 2-(5-methyl-2-phenyl-2<i>H</i>-1,2,3-diazaphosphol-4-yl)-derivatives of 1,4,2- and 1,3,2-dioxaphosphepines as well as dichlorovinylphosphonate, being the product of Perkow reaction in the case of chloral.</p

Intricate Phase Behavior and Crystal Structure Features of Chiral <i>para</i>-Methoxyphenyl Glycerol Ether Forming Continuous and Partial Solid Solutions

Heterogeneous equilibria, crystallization, and polymorphism of chiral <i>para</i>-methoxyphenyl glycerol ether <b>1</b> have been inspected, and, as a result, the binary phase diagram and the Gibbs free energy vs temperature plot were constructed and analyzed. This enantiomeric system forms a stable racemic compound, which turns into an almost ideal continuous solution of the enantiomers in the crystalline phase at elevated temperatures. At room temperature the system represents a stoichiometric racemic compound and two symmetrical eutectoid invariants with partial solid solutions based on the enantiomers. Crystal structures of the true racemate, the pseudoracemate, and the pure enantiomer were investigated by single crystal X-ray diffraction. The true racemate crystallizes in the <i>Pc</i> space group with <i>Z</i>′ = 2. The pseudoracemate was solved in the <i>Pbcn</i> group with the only independent molecule equally disordered into two mirror-related positions. The enantiomeric crystals belong to the <i>P</i>2₁2₁2 group and are characterized by six symmetry independent molecules (<i>Z</i>′ = 6), two of which undergo disordering. We also discussed possible connection between the phase behavior features and the details of the crystal structure, in particular, bilayer supramolecular organization, pseudosymmetry, high <i>Z</i>′, and disordered packing. General considerations about the crystalline nature of solid solutions of enantiomers were also made

A Supramolecular Amphiphile Based on Calix[4]resorcinarene and Cationic Surfactant for Controlled Self-Assembly

A novel supramolecular system based on calix[4]­resorcinarene sulfonatoalkylated at the lower rim and piperidine-methylated at the upper rim and the cationic surfactant hexadecyl-1-azonia-4-azobicyclo[2.2.2]­octane bromide was investigated by methods of NMR, tensiometry, conductometry, potentiometry, dynamic light scattering, X-ray powder diffraction, and spectral probe techniques. Both types of molecules were found to self-associate in aqueous solution, with aggregates of different morphology formed. Importantly, a supramolecular amphiphilic binary system with controlled structure and binding behavior could be fabricated. At high surfactant concentration, the formation of its own aggregates takes place. In the systems with the excess of cyclophane the supramolecular amphiphiles are formed, which, in turn, self-assemble in particles with a large hydrophobic core. Thereby the structure of supramolecular species is determined by relative fractions of components and, hence, could be selectively controlled. The found properties can be used for the design of nanocontainers with the controlled cavity size