Gas chromatographic enantioseparation of unfunctionalized chiral alkanes: A challenge in separation science (overview, state of the art, and perspectives)

Abstract

The chromatographic enantioseparation of small unfunctionalized chiral alkanes C*HR(1)R(2)R(3) (R = alkyl) represents a challenge in separation science. Because of the lack of any functional groups, enantiorecognition in the presence of a chiral selector is solely based upon weak enantioselective Van der Waals forces. Racemic alkanes containing seven and eight carbon atoms, i.e. 3-methylhexane (C7), 2,3-dimethylpentane (C7), 3-methylheptane (C8), 3,4-dimethylhexane (C8), 2,4-dimethylhexane (C8), 2,3-dimethylhexane (C8), and 2,2,3-trimethylpentane (C8) have been gas chromatographically enantioseparated on different modified cyclodextrins. The substitution pattern and cavity size of the cyclodextrin selectors have a pronounced effect on the degree of enantiorecognition observed. Thermodynamic parameters of enantiorecognition between four chiral alkanes and octakis(6-O-methyl-2,3-di-O-pentyl)-gamma-cyclodextrin (Lipodex G) have been determined. The possible role of molecular inclusion is indicated by the complete loss of enantioselectivity when the cyclodextrins are replaced by the corresponding linear dextrins ("acyclodextrins"). The enantioseparations of all seven chiral C7-C8 alkanes, six of them simultaneously, has been achieved on mixed binary selector systems whereby two different modified cyclodextrins are present in one gas chromatographic column. The smallest chiral (nonisotopically labeled) allene, i.e., 2,3-pentadiene, has been resolved gas chromatographically on a cyclodextrin selector.

Salient Features of Enantioselective Gas Chromatography: The Enantiomeric Differentiation of Chiral Inhalation Anesthetics as a Representative Methodological Case in Point

“…However, in the case of cyclodextrin selectors, minor molecular association with n-alkanes has been detected [24]. This is also corroborated by the observation that chiral branched alkanes, devoid of any functionality, can be enantioseparated on modified cyclodextrins by GC [137,138]. A theoretical treatment of the retention-increment R 0 approach has been put forward for n-alkane reference standards which undergo a definite, albeit negligible, interaction with modified cyclodextrins [24].…”

Online coupling of enantioselective capillary gas chromatography with proton nuclear magnetic resonance spectroscopy

“…The thermodynamic Gibbs-Helmholtz parameters of enantiorecognition of 2,4-dimethylhexane by Lipodex G have been reported previously. 3 The enantioseparation factor increases from a 5 1.16 at 658C to a 5 1.53 at 258C. The published enantioselectivity factor of a 5 1.5 at 308C on octakis(6-O-methyl-2,3-di-O-pentyl)-g-cyclodextrin for the single GC experiment 3 could not be achieved for this GC-NMR setup.…”

“…3 The enantioseparation factor increases from a 5 1.16 at 658C to a 5 1.53 at 258C. The published enantioselectivity factor of a 5 1.5 at 308C on octakis(6-O-methyl-2,3-di-O-pentyl)-g-cyclodextrin for the single GC experiment 3 could not be achieved for this GC-NMR setup. The reduction of the enantioselectivity is due the higher oven temperature of 608C, which reduces the enantioselectivity of the stationary phase in the enthalpy-controlled region (below the enantioselective temperature).…”

“…1 Unfunctionalized saturated hydrocarbons, i.e., alkanes, consist of a wide range of constitutional and configurational isomers (including enantiomers), which are difficult to distinguish by mass spectrometry. The number of constitutional and configurational isomers is dependent on the total number of carbon atoms and is increased from 24 isomers for C8 to 3395.964 for C20, 2 which requires high separation performances 3 and powerful detection systems to achieve a correct structural assignment. Due to the nonexistent functionality, the gas chromatographic enantioseparation of simple chiral alkanes cannot be achieved by hydrogenbonding chiral selectors (e.g.…”

Enantiomer self‐disproportionation and chiral stationary phase based selective chiral separation of organic compounds

“…Therefore, purification, analysis, and application of chiral isomers have been the most active subject of investigation in chemical industry as well as in academic research, as its enantiomeric purity is a major concern. 4,5 Conventionally, different methods such as chiral pool, enzymatic separation, separation through resolving agent, asymmetric catalysis, chiral chromatography, fractional sublimation of non-racemic compounds, [6][7][8] and ESD have been used to acquire enantiomerically pure compounds. Still it is necessary to improve a few economical and environmental aspects such as (a) chiral pool is based on natural resources only; (b) enzymatic separation provides one form of isomer; (c) resolving agent is required in huge amount to attain the desired yield; (d) separation of product from catalyst is difficult in asymmetric catalysis, and it leads to the degradation of an expensive catalyst.…”