Gas Chromatographic Separation Of Enantiomers Research Articles

Separating Enantiomers of Haloalkanes and Alcohols on a Stationary Phase Based on the Supramolecular Structure of Melamine with Induced Chirality

A new chiral stationary phase is proposed that is based on the supramolecular structure of melamine self-assembled in the mode of the induction of chirality. Induction is achieved via mechanical stirring in accordance with the Kondepudi effect in order to form a layer of a supramolecular structure with predominantly one type of chiral supramolecular domains on the surface of the sorbent. The resulting inert support with 1% melamine is used for the gas chromatographic separation of enantiomers of 2-butanol, 1‑methoxy-2-propanol, 2-bromobutane, 2-chlorobutane, and 2-bromopentane. The coefficients of selectivity and the separation of enantiomers are calculated. No separation of enantiomers is observed on a column conditioned at 100°C. After conditioning the column at 200°C, a series of successful separations of racemates is obtained in the 60–110°C range of temperatures. The highest coefficient of selectivity for haloalkanes is obtained at 70–75°C, so 2-bromobutane has α = 1.62 at 70°C, 2-chlorobutane has α = 1.23 at 75°C, and 2‑bromopentane has α = 1.68 at 70°C. The coefficients of selectivity for 2-butanol and 1-methoxy-2-propanol are highest at 80 and 100°C (α = 1.45 and 2.24), respectively. It is assumed that the ability of the suprastructure of melamine to exhibit enantioselectivity is associated with the formation of cavities capable of chiral recognition.

Separation of 2-Bromobutane, 2-Chlorobutane, 2-Chloropentane, and 2-Butanol Enantiomers Using a Stationary Phase Based on a Supramolecular Uracil Structure

We proposed a new chiral stationary phase based on a supramolecular uracil structure with induced chirality. According to the Kondepudi effect, mechanical stirring leads to the formation of a supramolecular structure layer on the surface of an adsorbent with a predominance of one of types of chiral supramolecular clusters. The obtained stationary phase was used for the gas-chromatographic separation of enantiomers of 2-bromobutane, 2-chlorobutane, 2-chloropentane, and 2-butanol. The effectiveness of a 1-m column packed with an inert stationary phase modified with uracil is 200–400 theoretical plates. The enantiomers of 2-bromobutane and 2-chlorobutane were completely separated using the proposed stationary phase in 210 and 180 s, respectively, at 45°C. The enantiomers of 2-chloropentane were separated at 60 and 65°C in 170 and 160 s, respectively. The enantiomers of 2-butanol were partially separated at 100°C. The enantioselectivity of the proposed stationary phase is probably associated with the adsorption of one enantiomer outside the cavity of the supramolecular structure and the other enantiomer inside it.

ChemInform Abstract: Gas Chromatographic Enantiomer Separation of Polychlorinated Biphenyls (PCBs): Methods, Metabolisms, Enantiomeric Composition in Environmental Samples and Their Interpretation

AbstractReview: 108 refs.

Effects of the dynamic modification of stationary phases by sorbates in gas chromatography: The possibility of separating enantiomers in achiral systems

It is shown that the gas chromatographic separation of enantiomers on columns with achiral nonpolar stationary phases is principally possible as a result of the dynamic modification of stationary phases by sorbates under analysis. It is found that a number of key characteristic features is intrinsic to such separation: it can be only partial, it does not occur for all chromatographic columns, and it is observed only for some compounds and only within narrow ranges of quantities of sorbates that are close to the limits of mass overload of chromatographic systems. These characteristic features are illustrated by the examples of separating (1R,5R)-(+)- and (1S,5S)-(−)-α-pinenes on a WCOT column with an RTX-5 phase. The main characteristic feature of the separation of enantiomers as a result of the dynamic modification of stationary phases is the nonconformity of peaks in chromatograms with two individual enantiomers, compared to other ways and means for their separation; the first eluting peak belongs to the enantiomer that predominates in a mixture irrespective of its configuration, while the second peak corresponds to the racemic mixture of enantiomers; i.e., the ratio of peak areas in chromatograms does not correspond to the actual ratio of enantiomers in samples under analysis and is strongly distorted as a result of their incomplete separation. It is concluded that the separation of racemic mixtures in achiral systems is fundamentally impossible under any conditions, and this is one of the key criteria of the validity of the considered concept as a whole.

Gas Chromatographic Enantiomer Separation of Polychlorinated Biphenyls (PCBs): Methods, Metabolisms, Enantiomeric Composition in Environmental Samples and their Interpretation

AbstractThe year 2016 not only marks the 50th anniversary of the first successful discovery of gas chromatographic (GC) enantiomer separations in 1966 by Gil‐Av, but also the less appraised 50th anniversary of the discovery of polychlorinated biphenyls (PCBs) in the environment. This article reports on GC enantiomer separations of axially stable, chiral PCBs (PCB atropisomers) with modified cyclodextrins. Nineteen atropisomeric PCBs exist, but most data exists for four PCB atropisomers (PCB 95, PCB 132, PCB 149, and PCB 136), which can be resolved without significant coelutions on three columns coated with modified cyclodextrins. Nonracemic compositions of PCB atropisomers and their hydroxylated metabolites have been documented in various studies. However, the measured enantiomer fractions are currently difficult to interpret und understand. The most plausible reasons for these difficulties are discussed and interpreted with the help of selected examples from the literature.

GC separation of enantiomers of alkyl esters of 2-bromo substituted carboxylic acids enantiomers on 6-TBDMS-2,3-di-alkyl- β- and γ-cyclodextrin stationary phases.

The gas chromatographic separation of enantiomers of 2-Br carboxylic acid derivatives was studied on four different 6-TBDMS-2,3-di-O-alkyl- β- and -γ-CD stationary phases. The differences in thermodynamic data {ΔH and -ΔS} for the 15 structurally related racemates were evaluated. The influence of structure differences in the alkyl substituents covalently attached to the stereogenic carbon atom, as well as in the ester group of the homologous analytes, and the selectivity of modified β- and γ- cyclodextrin derivatives was studied in detail. The cyclodextrin cavity size, as well as elongation of alkyl substituents in positions 2 and 3 of 6-TBDMS-β-CD, also affected their selectivity. The quality of enantiomeric separations is influenced mainly by alkyl chains of the ester group of the molecule and this appears to be independent of the CD stationary phase used. In some cases the separations occur as the result of external adsorption rather than inclusion complexations with the chiral selector. It was found that the temperature dependencies of the selectivity factor were nonlinear.

GC separation of 2‐substituted ethyl propionate enantiomers on permethylated and 2,6‐dimethyl‐3‐pentyl β‐ and γ‐cyclodextrin stationary phases

In this work, the capillary gas chromatographic enantiomer separation of eight congeneric compounds with general formulae CH3-HCX-COOC2H5 (where X = Cl, Br, I, CN, OH, OC2H5, OC6H5 and NHCOCF3) on four different permethyl- and 2,6-di-O-methyl-3-O-pentyl- beta- and gamma-CD stationary phases has been studied. The separation of enantiomers was evaluated in terms of the interactions of the X substituent of studied derivatives, as well as the nature of the 3-O-alkyl group in the 2,6-di-O-methyl-3-O-alkyl-CDs and the CDs cavity size. The differences in thermodynamic data [deltaH and -deltaS] obtained for studied compounds and the selectivity of modified beta- and gamma-cyclodextrin phases in gas chromatographic separation were evaluated. deltaH values were compared with a deltaH value of an achiral standard (ethyl propionate, where X = H) in order to obtain the contribution of a particular substituent to the overall interaction energy. It was shown that the variation in the enantiomeric separation with temperature and the retention order of these compounds on a given cyclodextrin capillary column depends on the nature of the substituents bonded to stereogenic carbon atom. It was found that the temperature dependencies of selectivity factors, In a on 1/T, were both linear as well as non-linear, inter alia depending on the number of glucopyranose units of the CD derivatives. The enantiospecific thermodynamic data [delta21(deltaH)] and [-delta21(deltaS)] which characterize the chiral recognition in the separation system were used to gain more insight into the mechanistic aspects of the enantioseparations on permethylated and 2,6-di-O-methyl-3-O-pentyl-beta- and gamma-cyclodextrins.

2,3-Di- O-methoxymethyl-6- O- tert-butyldimethylsilyl-β-cyclodextrin, a useful stationary phase for gas chromatographic separation of enantiomers

Heptakis(2,3- di- O-methoxymethyl-6- O- tert-butyldimethylsilyl)-β-cyclodextrin (2,3-MOM-6-TBDMS-β-CD), synthesized by using methoxymethylchloride (MOM-Cl) as derivatization reagent, was used for capillary gas chromatographic separation of enantiomers. The new chiral stationary phase proved to be suitable for the enantiodifferentiation of volatiles from various chemical classes. Compared to the corresponding γ-CD derivative (2,3-MOM-6-TBDMS-γ-CD), the spectrum of compounds for which enantiomers could be separated was more limited and the enantioseparation achieved was generally less pronounced. Unusually high separation factors were observed for 2-alkyl esters of short chain acids (C 2–C 6). Phenomena underlying the enantioseparation of 2-pentyl acetate ( α: 4.31; 35 °C) were investigated by determining thermodynamic parameters. Data show that only one enantiomer is retained significantly on the chiral stationary phase whereas the other one behaves like the hydrocarbons used as references.

2,3-Di-O-methoxymethyl-6-O-tert-butyldimethylsilyl-γ-cyclodextrin: a new class of cyclodextrin derivatives for gas chromatographic separation of enantiomers

Octakis(2,3-di-O-methoxymethyl-6-O-tert-butyldimethylsilyl)-gamma-cyclodextrin (2,3-MOM-6-TBDMS-gamma-CD) was employed as stationary phase for capillary gas chromatographic separation of enantiomers. Selective introduction of the acetal function at positions 2 and 3 of the glucose units was achieved by reaction of 6-O-TBDMS-gamma-cyclodextrin with methoxymethyl chloride. 2,3-MOM-6-TBDMS-gamma-CD was shown to be a chiral stationary phase suitable for enantiodifferentiation of a broad spectrum of chiral volatiles from various chemical classes. A total of 125 pairs of enantiomers could be separated. Structural influences of the analytes on the enantioseparation were demonstrated. High alpha values up to 1.8 were observed for the hydroxyketone acetoin and some methyl branched ketones. Pronounced enantioseparations were also determined for cyclic pentenolone and furanone derivatives.

Chromatographic enrichment and enantiomer separation of axially chiral polybrominated biphenyls in a technical mixture

The separation properties of different chromatographic methods regarding the enantioselective separation of axially chiral (atropisomeric) polybrominated biphenyls (PBB) were studied. For this purpose, the technical hexabromobiphenyl product Firemaster BP-6 ® was characterised by gas-chromatography coupled to electron capture detection (GC/ECD) and electron-capture negative ion mass spectrometry (GC/ECNI-MS) as well as by liquid chromatographic fractionating on active carbon and celite. Twelve individual PBBs including potential atropisomeric PBBs were isolated from Firemaster BP-6 by reversed-phase high-performance liquid chromatography (HPLC) on three serially coupled octadecylsilane columns. Six of the 12 isolated PBBs (three tri- ortho and di- ortho substituted PBBs, respectively) were separated into atropisomers on a HPLC column containing permethylated β-cyclodextrin on silica. Moreover, the temperature dependency of the enantiomer separations is discussed. Gas chromatographic enantiomer separation of PBBs is a very demanding task due to high elution temperatures. However, the atropisomers of one tri- ortho substituted PBB congener (PBB 149) could be resolved on a column coated with randomly modified heptakis(6- O- tert.-butyldimethylsilyl-2,3-di- O-methyl)-β-cyclodextrin in OV 1701.

Evaluation of non-polar interactions in chiral recognition by alkylated β- and γ-cyclodextrin chiral stationary phases

The gas chromatographic separation of enantiomers of seven N-TFA-O-alkyl amino acid derivatives was studied on four different permethyl- and 2,6-di-O-methyl-3-O-pentyl-β- and -γ-CD stationary phases.It was shown that the separation of enantiomers N-TFA-O-alkyl amino acid derivatives depends both on the length of the linear alkyl chain attached to the stereogenic carbon (R 1 ) and to the ester part of the amino acid derivative (R 2 ). The cyclodextrin cavity size also affected selectivity. The separation of the amino acid derivatives decreases with increasing length of both the R 1 and R 2 alkyl chains on β-CD stationary phases, but improves on γ-CD stationary phases. The separation of enantiomers of all N-TFA-O-methyl amino acid esters, is better on the larger γ-cyclodextrin CSPs except for enantiomers of N-TFA-O-alkyl esters of alanine which are better separated on β-CD stationary phases.

Gas Chromatographic Enantiomer Separation of Atropisomeric PCBs Using Modified Cyclodextrins as Chiral Phases

Gas chromatography (GC) has been utilized for the study of enantiomer resolution of the atropisomers of PCBs, o,p´-DDD and o,p´-DDT. Different substituents and concentrations of cyclodextrin, capillary dimensions and type of stationary phase films have been investigated to achieve the resolution of as many of the atropisomers on one column as possible. The results indicated that the butyl substitution of 6-hydroxyl and the methyl substitution of 2- and 3-hydroxyl were the most promising for the enantiomeric separation. Using Capillary Electrophoresis (CE), the trimers and monomers of PM-β-CDs were compared for enantiomeric resolution, as well as comparing the cationic PMMA-β-CD with the anionic HS-β-CD. In these studies the trimer did not show an improved resolution for mepivacaine, when compared to the equimolar concentration of the monomer. The cationic CD gave increased resolution values for ibuprofen when compared to the anionic CD. A scheme for reversing enantiomeric elution order of both the basic propranolol and acidic ibuprofen is also presented, with the aim of facilitating the detection of impurities in a high sample loading. The detection of 1% of each enantiomer of propranolol, and 1% of R(-)-ibuprofen, was demonstrated, with elution prior to the tailing peak of the corresponding enantiomer. Dimethylacrylamide-coated capillaries were used in this work, and the stability of this coating was demonstrated, giving a highly reduced electroosmotic flow for up to six months. Enantiomeric baseline separations of omeprazole and 5-hydroxyomeprazole have also been achieved with both CE and Open Tubular Capillary Electrochromatography (OT-CEC) methods. With CE-UV, both a non-aqueous method (using HDMS-β-CD) and an aqueous method (using HS-β-CD) were used for enantiomeric resolution of the two racemates. Resolution of omeprazole was also achieved using CE-Electrospray Ionization-Mass Spectrometry (ESI-MS). In OT-CEC, avidin was immobilized on the inside surface of a fused silica capillary and was employed as chiral selector for the enantiomeric baseline resolution of omeprazole and 5-hydroxyomeprazole.

Gas Chromatographic Enantiomer Separation of Atropisomeric PCBs Using Modified Cyclodextrins as Chiral Phases

Gas Chromatographic Enantiomer Separation of Atropisomeric PCBs Using Modified Cyclodextrins as Chiral Phases

Gas chromatographic enantiomer separation on single and mixed cyclodextrin derivative chiral stationary phases

Capillary gas chromatographic enantiomer separation of some polar compounds, including α-phenylethylamine, styrene oxide, pyrethroid insecticides and other carboxylates, was investigated on modified cyclodextrin (CD) chiral stationary phases. The chiral stationary phases studied included permethylated β-CD (PMBCD), heptakis (2,6-di-O-butyl-3-O-butyryl)-β-CD (DBBBCD), heptakis (2,6-di-O-nonyl-3-O-trifluoroacetyl)-β-CD (DNTBCD), the mixture of PMBCD and DBBBCD, and the mixture of PMBCD and DNTBCD. On the mixed chiral stationary phases containing the mixtures of derivatized cyclodextrins, enantiomer separation was improved significantly for some compounds as compared to the single cyclodextrin derivative chiral stationary phases, and synergistic effects were observed for some compounds on the mixed cyclodextrin derivative chiral stationary phases.

Enantiomer separation of α-ionone using gas chromatography with cyclodextrin derivatives as chiral stationary phases

The gas chromatographic enantiomer separation of α-ionone was studied with three different chiral stationary phases using as chiral selectors: (1) heptakis(2,3,6-tri- O-methyl)-β-cyclodextrin, dissolved in polysiloxane PS-086, (2) octakis(2,6-di- O-pentyl-3- O-trifluoroacetyl)-γ-cyclodextrin and (3) octakis(2,6-di- O-pentyl-3- O-butanoyl)-γ-cyclodextrin, both dissolved in polysiloxane SE-54. The influence of the concentration of the chiral selector in the polysiloxane, coated on Chromosorb P AW-DMCS 80–100 mesh, is described and discussed, as well as the effect of Chromosorb loading. The feasibility of the preparative gas chromatographic separation of the enantiomers of α-ionone is considered; in order to provide a term of comparison, the estimated performances are compared with those achieved in the separation of the enantiomers of the inhalation anaesthetic enflurane.

Gas chromatographic enantiomer separation of C-3 and C-4 synthons: prediction of absolute configuration from elution order and enzymatic resolution

Enantiomers of C-3 secondary alcohols, 3-hydroxybutanoates, and cyclic 1,3-dithioacetals were separated by chiral GLC using CP-Chirasil-Dex CB and Chiraldex G-TA columns. The former was most successful for analysis of n-alkyl esters of secondary alcohols and the separation depended on the chain length of the acyl group and the electronic and steric properties of the other substituents. The Chiraldex G-TA column was efficient for analysis of secondary alcohols, derivatized as their trifluoroacetates. The elution order of the secondary alcohols and the corresponding acetates was always the same with respect to the size of groups connected to the stereocenter. However, when the secondary alcohols were analyzed as their trimethylsilyl derivatives, the elution order was reversed. Elution order on chiral columns and enantiomeric ratios, E-values, obtained in kinetic resolutions catalyzed by lipase B from Candida antarctica (CALB) were evaluated as a method for prediction of absolute configuration. The usefulness of the method was demonstrated using 22 pairs of enantiomers. Copyright 1999 Wiley-Liss, Inc.

Dynamic phenomena involving chiral dimethyl-2,3-pentadienedioate in enantioselective gas chromatography and NMR spectroscopy

The chiral allene dimethyl-2,3-pentadienedioate 1 undergoes enantiomerization during gas-chromatographic enantiomer separation on the two polymeric chiral stationary phases Chirasil-Nickel 2a and Chirasil-Dex 3 at ambient temperatures. The enantiomerization barrier of 1 is determined by dynamic gas chromatography via computer simulation of interconversion elution-profiles and by multidimensional stopped-flow gas chromatography. The previously reported deracemization of 1 in the presence of a chiral paramagnetic lanthanide shift reagent by NMR spectroscopy is confirmed.

Use of the equilibrium-dispersive model of nonlinear gas chromatography for the modelling of the elution band profiles in the preparative-scale gas chromatographic separation of enantiomers

The equilibrium-dispersive model of chromatography is applied to the study of enantioselective separations of methyl 2-chloropropionate in gas chromatography. The single-component and competitive bi-Langmuir isotherm equations that describe the sorption behavior of single enantiomers and racemates, respectively, are utilized by the equilibrium-dispersive model to predict the elution band profiles of single-component and binary mixture samples. The measured and the calculated band profiles are compared both for the analytical open tubular column used to acquire the isotherm data and for the 1 m×22.5 mm I.D. preparative packed column, followed by the comparison of the enantiomeric purity vs. production curves for both the measured and the simulated systems.

Determination of the gas-liquid partition isotherms of the enantiomers of methyl 2-chloropropionate on trichloroacetyl pentyl β-cyclodextrin using the elution by characteristic points method

The gas-liquid partition isotherms of the enantiomers of methyl 2-chloropropionate on a trichloroacetyl pentyl β-cyclodextrin stationary phase were determined at three different temperatures using the elution by characteristic points method. The isotherms were described using the single-component and competitive bi-Langmuir isotherm equations. The measured and calculated isotherms as well as the retention factor and separation selectivity data agree, indicating that these isotherms might be suitable for the modeling of the preparative-scale gas chromatographic separation of the enantiomers.

Chiral interactions of the fluoroether anesthetics desflurane, isoflurane, enflurane, and analogues with modified cyclodextrins studied by capillary gas chromatography and nuclear magnetic resonance spectroscopy: A simple method for column-suitability screening

Eighteen chiral analogues of the chiral fluoroether anesthetics desflurane, isoflurane, and enflurane are synthesized and studied by capillary GC on four cyclodextrin-derived stationary phases. Trends in separability and elution order of enantiomers are related to structure and absolute configuration. In particular, a very large separation factor is found for the commercial anesthetic desflurane using Lipodex® E stationary phase, suggesting that a preparative enantiomer separation is possible. One of the stationary phases, Cyclodex® G-TA, is found to be a chiral shift reagent for several of the fluoroethers. A rough correspondence is found relating the enantiomeric separation factor of a fluoroether and the chemical shift differences between its 1H and 19F nuclei in the NMR spectrum. Based on this data, it is proposed that a simple NMR experiment can screen chiral stationary phases prior to a desired gas chromatographic enantiomer separation of a given chiral compound.