Chiral phases Pirkle

Many types of chiral stationary phase are available. Pirkle columns contain a silica support with bonded aminopropyl groups used to bind a derivative of D-phenyl-glycine. These phases are relatively unstable and the selectivity coefficient is close to one. More recently, chiral separations have been performed on optically active resins or cyclodextrins (oligosaccharides) bonded to silica gel through a small hydrocarbon chain linker (Fig. 3.11). These cyclodextrins possess an internal cavity that is hydro-phobic while the external part is hydrophilic. These molecules allow the selective inclusion of a great variety of compounds that can form diastereoisomers at the surface of the chiral phase leading to reversible complexes. 

The separation of enantiomers can be effected either by transforming them into diastereoisomers using a chiral reagent and separating them on conventional phases or by separating the enantiomers on chiral phases. The utilization of chiral phases has not yet become routine, but studies of enantiomeric dipeptides have been carried out (115,116). Pirkle et al. (117) and Hyun et al. (118) separated enantiomeric di- and tripeptides (methyl esters of /V-3-5-dinitrobenzoyl derivatives) on chiral stationary phases (CSPs) derived from (R)-a-arylalkylamines, (S)-N-(2-naphthyl) valine, or (S)-1 -(6,7-dimethyl-1 -naphthyl) isobutylamine. These workers were able to separate four peaks for each dipeptide derivative, corresponding to the two enantiomeric pairs (R,R)/(S,S) and (R,S)/(S,R). Cyclodextrin-bonded stationary phases and chiral stationary immobilized a-chymotrypsin phases were used to separate enantiomeric peptides (118a,b). 

Few chiral phases are used in TLC one of the main reasons for this is that stationary phases with a very high ultraviolet (UV) background can be used only with fluorescent or colored solutes. For example, amino-modified ready-to-use layers bonded or coated with Pirkle-type selectors [3], such as A-(3,5-dini-trobenzoyl)-L-leucine or i (—)-a-phenylglydne, are pale yellow and strongly adsorb UV radiation. 

Figure 10.3 Representative bonded chiral phases for HPLC. (I) Pirkle phase (II) N-(3, 5-dinitrobenzoyl) phenylglycine ionically bonded to 3-asinopropylsilanized silica (III) N-n-valeryl-L-valyl-3-aminopropylsilanized silica (IV) R-(-)-2-(2-4-5-7-tetranitro-9-fluorenylideneaminooxy) propionamidepropyl silanized silica.

Huvalinate Fluvahnate has two enantiomer pairs and four isomers (2 = 4). Gao et al. (1998) separated the enantiomer pairs (I, A + D II, B + C) on a Pirkle-type chiral phase HPLC column (Table C9, Appendix C). Yang et al. (2004) used a CHIRALCEL... 

A two-phase Pirkle modified amino-bonded phase for enantiomer separation was prepared by partially immersing a commercial HPTLC NH2 F-plate (Merck) in a solution of the chiral selector Af-(3,5-dinitrobenzoyl)-L-leucine. The portion of the plate modified with chiral selector was used to separate the enantiomers of the model compounds 2,2,2-trifluoro-(9-anthryl)ethanol and l,l -binaphthol with the mobile phase hexane/isopropanol (80 20). The separated enantiomers were then eluted using continuous development onto the unmodified portion of the plate. The absence of the selector on this segment of the layer allowed the detection of the separated compounds by fluorescence quenching [20]. 

Witherow, L., Sprurway, T.D., Ruane, R.J. and Wilson, I.D., Problems and solutions in chiral thin-layer chromatography a two-phase Pirkle modihed amino-bonded plate, J. Chromatogr., 553, 497-501, 1991. 

Nonpolar organic mobile phases, such as hexane with ethanol or 2-propanol as typical polar modifiers, are most commonly used with these types of phases. Under these conditions, retention seems to foUow normal phase-type behavior (eg, increased mobile phase polarity produces decreased retention). The normal mobile-phase components only weakly interact with the stationary phase and are easily displaced by the chiral analytes thereby promoting enantiospecific interactions. Some of the Pirkle-types of phases have also been used, to a lesser extent, in the reversed phase mode. 

W. H. Pirkle and B. C. Hamper, The direct preparative resolution of enantiomers by liquid chromatography on chiral stationary phases in Preparative Liquid Chromatography, B. A. Bidling-meyer (Ed.), Journal Chromatography Library Vol. 38, 3 Edition, Elsevier Science Publishers B. V, Amsterdam (1991) Chapter 7. 

Small chiral molecules. These CSPs were introduced by Pirkle about two decades ago [31, 32]. The original brush -phases included selectors that contained a chiral amino acid moiety carrying aromatic 7t-electron acceptor or tt-electron donor functionality attached to porous silica beads. In addition to the amino acids, a large variety of other chiral scaffolds such as 1,2-disubstituted cyclohexanes [33] and cinchona alkaloids [34] have also been used for the preparation of various brush CSPs. 

The brush-type (Pirkle-type) CSPs have been used predominantly under normal phase conditions in LC. The chiral selector typically incorporates tt-acidic and/or n-basic functionality, and the chiral interactions between the analyte and the CSP include dipole-dipole interactions, n-n interactions, hydrogen bonding, and steric hindrance. The concept of reciprocity has been used to facilitate the rational design of chiral selectors having the desired selectivity [45]. 

Popova and colleagues47 carried out TLC of oxidation products of 4,4 -dinitrodiphenyl sulphide (the sulphoxide and sulphone) on silica gel + a fluorescent indicator, using hexane-acetone-benzene-methanol(60 36 10 l) as solvent mixture. Morris130 performed GLC and TLC of dimethyl sulphoxide. For the latter, he applied a 6% solution of the sample in methanol to silica gel and developed with methanol-ammonia solution(200 3), visualizing with 2% aqueous Co11 thiocyanate-methanol(2 1). HPLC separations of chiral mixtures of sulphoxides have been carried out. Thus Pirkle and coworkers131-132 reported separations of alkyl 2,4-dinitrophenyl sulphoxides and some others on a silica-gel (Porosil)-bonded chiral fluoroalcoholic stationary phase, with the structure ... 

There is a wide variety of commercially available chiral stationary phases and mobile phase additives.32 34 Preparative scale separations have been performed on the gram scale.32 Many stationary phases are based on chiral polymers such as cellulose or methacrylate, proteins such as human serum albumin or acid glycoprotein, Pirkle-type phases (often based on amino acids), or cyclodextrins. A typical application of a Pirkle phase column was the use of a N-(3,5-dinitrobenzyl)-a-amino phosphonate to synthesize several functionalized chiral stationary phases to separate enantiomers of... 

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