Crystallization Of Enantiomers Research Articles

Chiral crystallization of glutamic acid on self assembled films of cysteine

In this article, we describe the preparation and use of chiral surfaces derived from enantiomerically pure crystals of amino acids. For this purpose, we chose to employ a self-assembly process to grow nanoscale chiral films of (+)-L or (-)-D cysteine, onto gold surfaces. We utilized those chiral films as resolving auxiliaries in the crystallization of enantiomers from solutions. To demonstrate the chiral discriminating ability of the chiral surfaces in crystallization processes, we investigated the crystallization of rac-glutamic acid onto the chiral films. Our study demonstrates the potential application of chiral films to control chirality throughout crystallization, where one enantiomer crystallizes on the chiral surfaces with relatively high enantiomeric excess. In addition, crystallization of pure glutamic acid enantiomers, and its racemic compound on to chiral films resulted in crystal morphology modification with preferred crystal orientation, which assists in the interpretation of the ability of our chiral surfaces to function as chiral selectors.

Simulated Moving Bed (SMB) Separation of Pharmaceutical Enantiomers and Crystallization

A promising solution for the separation of pharmaceutical enantiomers is the method of SMB liquid chromatography (SMB-LC). An optimised coupling of SMB-LC and crystallization processes can improve the efficiency of enantioseparation. In the first process both enantiomers can be produced in enriched concentrations in extract and raffinate streams of simulated moving bed chromatograph suitable for crystallization. Chromatographic investigations include the experimental determination of adsorption isotherms, bed voidage, NTP, HETP etc. on a suitable chiral stationary phase as well as the simulation and optimization of a the appropriate SMB-LC process. Mathematical models and joined computer programmes were published in our earlier papers had been developed and applied for the calculation of SMB-LC. We assumed isotherm, isochor equilibrium adsorption (competitive multicomponent Langmuir-adsorption equilibrium) in the mathematical model neglecting the effects of axial dispersion. The mathematical model was solved by finite differences, numerical mathematical method using PC. The SMB-LC separations were carried out on a laboratory scale (I.D.=1 cm, L=25 cm) four-column open loop eluent system equipment at 1:1:1:1 column configuration. The process variables of the SMB-LC (product purity, yield, productivity, specific solvent consumption) are favourable. The efficiency of the enantiomer separation can be increased by coupled crystallization of the enriched extract and raffinate fractions resulting >99% (w/w) pure enantiomer crystals. „Mother liquids” recirculation from crystallization to the SMBLC process increases with great benefit the economical parameters of enantiomer separation.

Optimization of the local crystallization processes of preparing chiral drugs in periodic crystallizers

The regularities of periodic processes of local crystallization of enantiomers and the kinetics of nucleation and growth of crystals are considered. The criteria for optimization of technological processes of preparing chiral drugs with the aim of attaining the maximum yield of final products with a required optical purity are formulated on the basis of experimental data.

Formation of racemic compound crystals by mixing of two enantiomeric crystals in the solid state. Liquid transport of molecules from crystal to crystal

Mixing of powdered (-)- and (+)-enantiomer crystals in the solid state gives crystals of the racemic compound. This racemic crystal formation was followed by IR spectral measurement of a 1∶1 mixture of (-)- and (+)-enantiomer crystals as a Nujol mull. As the formation of racemic crystals proceeds, the OH absorptions of the enantiomer disappear gradually and new OH absorptions due to the racemic compound appear. The formation of racemic crystals from enantiomer crystals has been studied for various kinds of chiral compounds: 2,2′-dihydroxy-1,1′-binaphthyl (1) and its derivatives, 10,10′-dihydroxy-9,9′-biphenanthryl (4), 2,2′-dihydroxy-4,4′,6,6′-tetramethylbiphenyl (5) and its derivatives, 4,4′-dihydroxy-2,2′,3,3′,6,6′-hexamethylbiphenyl (8), 1,6-di(o-chlorophenyl)-1,6-diphenylhexa-2,4-diyne-1,6-diol (11) and its derivatives, trans-4,5-bis[hydroxy(diphenyl)methyl]-2,2-dimethyl-1,3- dioxacyclopentane (17) and its derivatives, tartaric acid (20) dimethyl tartrate (21), malic acid (22), mandelic acid (23), and norephedrine (24). These molecular movements and blending occur rapidly in the presence of liquids such as liquid paraffin (Nujol), seed oils such as olive, coconut, rapeseed and soybean oil, artificial oil such as silicone oil and water, although the same movement also occurs in the absence of the liquid. For example, keeping a mixture of powdered (-)-1 (1a) and (+)-1 (1b) at room temperature for 48 h gives racemic crystals (1c). However, molecular aggregation sometimes occurs in solution but not in the solid state. For example, recrystallization of (-)-16 (16a) and (+)-16 (16b) from solvent gives racemic crystals of 16c, although mixing of these two components as powders in the presence of liquid does not give 16c. In order to determine the mechanism of the molecular movement in the solid state, X-ray crystal structures of optically active and racemic compounds and also the molecular movements from optically active crystal to racemic crystal have been studied.

Polymorphism of Compound Existing as Both Racemic Compound Crystals and Mixed Crystals of Enantiomers

Abstract By recrystallization of certain racemic compound (ST), racemic compound crystals, mixed crystals of two enantiomers, or a mixture of these two types of crystals were obtained, depending on the recrystallization conditions employed. Their crystal forms were determined by X-ray diffraction of the single crystals and powdered materials. The space group and lattice parameters of the mixed crystals were identical with those of the enantiomeric crystals. This polymorphism of ST crystals would be ascribed to the small difference in the thermodynamic stability between the enantiomeric and racemic crystals. The physicochemical properties of ST are described, too.

Transition metal mediated asymmetric synthesis. II. Complete resolution of (2R,5S)-(-)-Tricarbonyl[1-5-η-(2-methoxy-5-methylcyclohexadienyl)]iron(1+) hexafluorophosphate(1 -) by selective crystallization of enantiomers

The resolution of tricarbonyl(1-5-η-cylcohexadienyl)iron(1+) salts can be achieved by selective crystallization of enantiomers. The magnitude of the specific rotatory power of the title salt (1) was increased to a limiting value which was shown to correspond to optical purity, by a direct, n.m.r. method, after alkylation with dimethyl malonate. Reduction of the optically active salt defined the absolute configuration of (2R,5S)-(+ )-tricarbonyl[l-4-η-(2-methoxy-5β-methylcyclohexa-1,3-diene)]-iron(0). The chiroptical properties of the products are discussed.