Chiral Selectivities of Permethylated α-, ß-, and γ-Cyclodextrins Containing Gas Chromatographic Stationary Phases towards Ibuprofen and Its Derivatives.

Ibuprofen is a well-known and broadly used, nonsteroidal anti-inflammatory and painkiller medicine. Ibuprofen is a chiral compound, and its two isomers have different biological effects, therefore, their chiral separation is necessary. Ibuprofen and its derivatives were used as model compounds to establish transportable structure chiral selectivity relationships. Chiral selectors were permethylated α-, ß-, and γ-cyclodextrins containing gas chromatographic stationary phases. The chiral selectivity of ibuprofen as a free acid and its various alkyl esters (methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and isoamyl esters) derivatives were tested at different temperatures. Every tested stationary phase was capable of the chiral separations of ibuprofen in its free acid form. The less strong included S optical isomers eluted before R optical isomers in every separate case. The results offer to draw transportable guidelines for the chiral selectivity vs. analyte structures. It was recognized that the S isomers of free ibuprofen acid showed an overloading phenomenon, but the R isomer did not. The results were supported by molecular modeling studies.

Structure-Chiral Selectivity Relationships of Various Mandelic Acid Derivatives on Octakis 2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl-gamma-cyclodextrin Containing Gas Chromatographic Stationary.

Frequently, a good chiral separation is the result of long trial and error processes. The three-point interaction mechanisms require the fair geometrical fitting and functional group compatibility of the interacting groups. Structure-chiral selectivity correlations are guidelines that can be established via trough systematic studies using model compounds. The enantiorecognition of the test compounds was studied on an octakis 2,3-Di-O-acetyl-6-O-tert-butyldimethylsilyl-gamma-cyclodextrin (TBDMSDAGCD) chiral selector. In our work, mandelic acid and its variously substituted compounds were used as model compounds to establish adaptable rules for other enantiomeric pairs. The mandelic acid and its modified compounds were altered at both their carboxyl and hydroxyl positions to test the key interaction forces of the chiral recognition processes. Ring- and alkyl-substituted mandelic acid derivatives were also used in our experiments. The chiral selectivity values of 20 test compounds were measured and extrapolated to 100 °C. The hydrogen donor abilities of test compounds improved their chiral selectivities. The inclusion phenomenon also played a role in chiral recognition processes in several cases. Enantiomer elution reversals were observed for different derivatives of hydroxyl groups, providing evidence for the multimodal character of the selector. The results of our research can serve as guidelines to achieve appropriate chiral separation for other enantiomeric pairs.

Novel Ring Systems: Spiro[Cycloalkane] Derivatives of Triazolo- and Tetrazolo-Pyridazines.

In orderto synthesize new pyridazine derivatives anellated with different nitrogen heterocyclic moieties, spiro[cycloalkane]pyridazinones were transformed into the corresponding thioxo derivatives via a reaction with phosphorus pentasulfide. The reaction of the formed 2,3-diazaspiro[5.5] undec-3-ene-1-thiones with hydrazine provided the corresponding 1-hydrazono-2,3-diazaspiro[5.5] undec-3-ene, whose diazotization led to the desired spiro[cyclohexane-1,8'-tetrazolo[1,5-b]pyridazines. The reaction of dihydropyridazinethiones with benzhydrazide afforded the corresponding 7H-spiro[[1,2,4]triazolo[4,3-b]pyridazin-8,1'-cyclohexanes]. As a result of our work, seven new pyridazinethione intermediates were prepared, which served as starting materials for the synthesis of two kinds of new ring systems: tetrazolo-pyridazines and triazolo-pyridazines. The six new annulated derivatives were characterized by physicochemical parameters. The new N-heterocycles are valuable members of the large family of pyridazines.