Nem lineáris összefüggések a királis vegyületek szelektív kölcsönhatásaiban = Non-linear relationships in selective interactions between chiral compounds.

Módszeresen vizsgáltuk a rokon molekulaszerkezetű racém vegyületek, illetve reszolválóágensek viselkedését a diasztereomerek elválasztásai során. Az enantiomer keverékek elválasztásainál a kapott nem lineáris lefutású ee0-ee görbék és az olvadási biner fázisdiagramjaik közötti hasonlóságot, (pl. az eutektikus összetételek egyezését) tapasztaltunk. Megállapítottuk, hogy a diasztereomer sók olvadási biner fázisdiagramjainak a nem lineáris lefutása a racém vegyület enantiomer keverékeinek a viselkedésének a függvénye. A rokon molekulaszerkezetű vegyületeink körében számos aminosav (N-acil-, vagy észter-) származékát vizsgáltuk. Megállapítottuk, hogy önmagukban, vagy szabad állapotban is felhasználhatóak enantiomerek elválasztására racém vegyület, vagy reszolválóágensként. Megállapítottuk, hogy az alfa- és gamma-aminosavak enantiomerjei, például „királis bázisként” jó enantiomer elválasztást eredményeznek. Ugyanakkor a diasztereomerek kristályosodásánál a kinetikus kontroll fellépését is megfigyeltük. A végzett elválasztások során a kristályos fázis kialakulásainak az azonosságai azt bizonyítják, hogy az enantiomer keverékek viselkedése meghatározza a diasztereomer keverékek viselkedését is. A végzett enantiomer és diasztereomer keverékek elválasztásai során szinte kivétel nélkül környezetbarát eljárásokat dolgoztunk ki, melyeknél oldószerként vizet alkalmaztunk. További P-kiralitáscentrumot tartalmazó heterociklusos racém vegyületek enantiomer elválasztásait oldottuk meg. | We have systematically studied the behaviour of structurally related racemic compounds and resolving agents during the separation of diastereoisomers. As it was assumed earlier, correlation between the non-linear ee0-ee curves and melting point phase diagrams was found during these separations, as similarities of eutectical compositions on the two diagrams were observed. Among the investigated compounds with related molecular structure, several (N-acylated, or ester-) derivatives of amino acids were examined. We established, that they can be applied for separation of enantiomers both as a racemic compound or resolving agent, in free state or as a derivative. We established that alpha- and gamma-amino acids, for example as „chiral base”, result in good enantiomeric enrichment. At the same time the kinetic control at the crystallisation of diastereomers was observed. On the basis of our own experimental results we can declare that the similarities of the crystalline phases prove that the behaviour of enantiomeric mixture also determines the behaviour of diastereomeric mixtures. Almost without exception, during the separation of all the enantiomeric and diastereomeric mixtures we worked out environmentally friendly methods, applying water as solvent. We successfully extended our resolution methods to the separation of further cyclic racemic compounds containing P-chiral centre unknown in literature in enantiopure form

New Opportunities to Improve the Enantiomeric and Diastereomeric Separations

The preparation of single enantiomers (ee ~100%) is one of the most important demands both for industrial practice and research. Actually, the resolution of the racemic compounds still remains the most common method for producing pure enantiomers on a large scale. To obtain the pure enantiomers, it is necessary to find the appropriate conditions and resolving agents. During the separation of diastereomeric mixtures, similar trends can be observed as in course of the distribution of enantiomeric mixtures between phases, because just the presence of one-third chiral compound (namely the resolving agent) is the difference. This chapter presents new observations and establishments about the new opportunities to optimize the separation of chiral mixtures, especially the diastereomeric mixtures

Separation of Chiral Compounds: Enantiomeric and Diastereomeric Mixtures

Despite the dramatic development of enantioselective synthesis and chromatographic separation methods, optical resolution still remains the cheapest and operationally simplest method for producing pure enantiomers on a larger scale. No extreme conditions or expensive reagents are required, and the eventually expensive resolving agents can be recovered. This chapter is based mainly on the authors’ long experience in the resolution of industrially important molecules, and it presents new observations and establishments as well. Several methods for separation of chiral mixtures, enantiomeric and diastereomeric mixtures, are shown, and possibilities for predicting the efficiency of resolution based on the analysis of physico-chemical properties of the reactants are also described

Prediction of the efficiency of diastereoisomer separation on the basis of the behaviour of enantiomeric mixtures

The composition of a crystalline diastereoisomer (eeDIA) is determined either by the eutectic composition of the racemic compound (eeEuRac) or that of resolving agent (eeEuRes) and the higher ee value has the more dominant effect.</p

Crystalline Forms of 4,4'-Methylenediantipyrine: Crystallographic Unit Cell for the Anhydrous Form, from Laboratory Powder XRD Pattern by DASH Program Package

Crystalline unit cell structure of anhydrous title compound, diantipyrinylmethane (CAS Registry No. 1251-85-0), a substance usually obtained as a by-product in Mannich type reactions of antipyrine, has been modelled by the help of powder X-ray diffraction, applying the DASH software package and crystal coordinates coming from former single crystal X-ray structure determinations (CSD codes FADDIY and FADDIY01) of its monohydrate. The unit cell of the anhydrate compound belongs to the monoclinic space group P21/a, with unit cell parameters of a = 14.604, b = 9.858, c = 14.509 Å, β = 95.56 °, V = 2078.9 Å3, Z = 4, Z ' = 1. Comparisons of FT-IR spectrum and thermal behavior of the anhydrous and monohydrated forms confirm differences in degree of hydration and solid state structure, while those of 1H- and 13C NMR-spectra show their molecular identity