Chiral polysiloxane

A number of ketones, pharmaceutical compounds, alcohols and hydroxy acids have also been resolved on this phase [724,765-767]. A chiral polysiloxane phase with tartramide substituents has been used for the separation of enantiomers capable of hydrogen bonding interactions with the stationary phase, such as enantiomers containing carboxylic, hydroxyl and amine functional groups [768]. 

The same is true for the chiral polysiloxanes described here. Their use as stationary phases in gas chromatography allows the calculation of the differences in enthalpy and entropy for the formation of the diaste-reomeric association complexes between chiral receptor and two enantiomers from relative retention time over a wide temperature range. Only the minute amounts of the polysiloxanes required for coating of a glas capillary are necessary for such determinations. From these numbers further conclusions are drawn on the stereochemical and environmental properties required for designing systems of high enantio-selectivity in condensed liquid systems. 

Figure 4. IR spectrum of a chiral polysiloxane prepared without spacing di-...

The applications of chiral polysiloxanes in enantiomer analysis in various fields of chemistry have been extensively reviewed6,124,128. Noteworthy is the use of Chirasil-Val (in both enantiomeric forms) for trace enantiomer analysis in the realm of EPC and enzymatic transformations31109. Enantiomeric impurities down to levels as low as <0,005% have been determined31185 (Figures 24a and 24b). 

From our own experience, it should be emphasised that the enantioselectivity of modified cyclodextrin phases is considerably influenced by the polarity of the (non-chiral) polysiloxane solvents used. 

Using a chiral column, coated with a definite modified cyclodextrin as the chiral stationary phase, the elution orders of furanoid and pyranoid linalool oxides are not comparable [11, 12]. Consistently, the chromatographic behaviour of diastereomers and/or enantiomers on modified cyclodextrins is not predictable (Fig. 17.1, Table 17.1). Even by changing the non-chiral polysiloxane part of the chiral stationary phase used, the order of elution may significantly be changed [13]. The reliable assignment of the elution order in enantio-cGC implies the coinjection of structurally well defined references [11-13]. 

B. Koppenhoefer and E. Bayer, Chiral recognition in gas cgromatographic analysis of enantiomers on chiral polysiloxanes./. Chromatogr. Library 32 (1985), 1. 

Y. Dobashi, K. Nakamura, T. Saeki, M. Matsuo, S. Hara, and A. Dobashi, New chiral polysiloxane derived from (R,R)-tartramide for enantiomer resolution by capillary gas chromatography,/. Org. Chem. 56 (1991), 3299. 

The major breakthrough in the GC enantiomer separation has been the work of Bayer and associates [23,76], who synthesized a silicone-based chiral phase, stable up to 240°C. As shown in Fig. 3.14, a racemic mixture of 19 protein amino acids can be separated [23] on a glass capillary column coated with Chirasil-Val, a chiral polysiloxane phase. The phase was synthesized through coupling L-valine-tert-butylamide to a copolymer of dimethylsiloxane and carboxyalkylmethylsiloxane. 

The unambiguous regioselective synthesis of chiral polysiloxane-containing CyDs as chiral stationary phases, with the mono-octamethylene spacer in either the 02, 03, or 06 position was performed and the products applied to enantio-selective GC separations [99]. Subtle differences in the chemistry of the hydroxyl groups at the 2-, 3-, and 6-positions of CyDs can be exploited to direct an electrophilic reagent to the desired site. Selective monoalkylation at the primary side of a-CyDs involves the reaction of a-CyD with 4-methylamino-3-nitrobenzyl chloride in 2,6-lutidine. Monoalkylation at the 2-position of j8-CyD is accomplished by the reaction of yS-CyD with l -bromo-4-methylamino-3-nitroacetophenone [100]. 

It is seen that the separation is completed in about 30 min., a much faster analysis than that of Gil-Av. It was found that the minimal operating temperature was 90°C, but the column could be programmed up to 175°C without column deterioration. As a result of the introduction of the chiral polysiloxane stationary phases by Frank et al, the development of chiral GC gained momentum. 

Chiral Stationary Phases for Gas Chromatography Small Molecule Stationary Phases Chiral Polysiloxane Stationary Phases Chiral Metal Chelating Stationary Phases Cyclodextrin Chiral Stationary Phases... 

Under reducing conditions with zine/HCl - -iminodipro-pionic acid (IDP) was isolated. IDP was already described in the literature by Karrer and Appenzeller (ref. 8), and occurs as RR and SS enantiomer and meso form. All forms were synthesized, and compared with the IDP obtained by degradation of amavadin. Since the amount of material was restricted a micromethod had to be devised for this purpose. Therefore capillary gas chromatography on Chirasil-Val (ref. 9, 10), a chiral polysiloxane peptide stationary phase was chosen. Very well resolved are the chiral forms of IDP as derivatization products with isopropyl isocyanate on Chirasil-L-Val, as is shown in Fig. 3. The IDP degradation product of amavadin is identical with SS-IDP. 

H. Frank. G. Nicholson and E. Bayer, Chiral polysiloxanes for resolution of optical antipodes, Angew.Chem.Int. 

The first effective chiral stationary phases for GC were the derivatized amino acids,which, however, had very limited temperature stability. The first reliable GC stationary phase was introduced by Bayer and coworkers,who synthesized a thermally stable, low-volatility polymer by attaching 1-valine-tbutylamide to the carboxyl group of dimethylsiloxane or (2-carboxypropyl)-methylsiloxane with an amide linkage. This stationary phase was eventually made available commercially as Chirasil-Val and could be used over the temperature range of 30°C to 230°C. OV-225 (a well-established polar GC stationary phase) has also been used for the synthesis of chiral polysiloxanes, which, in this case, possess more polar characteristics than the (2-carboxypropyl)-methylsiloxane derivatives. 

Another elegant example of the imitation of the properties of biopolymers by synthetic polymers comes from the school of E. Bayer of Tubingen (172). They have prepared chiral polysiloxane polymers for resolution of optical antipodes. The prochiral polymeric backbone was a copolymer of poly [(2-carboxypropyl)methylsiloxane], octamethylcyclotetrasiloxane, and hexa-methyldisiloxane. Amino acids or small peptides were covalently linked to this polymer in order to introduce a chiral surface. For this, the free carboxyl function of the polymer was reacted with the L-amino acid in the presence of DCC (see Chapter 2). The individual chiral centers (amino acids) on the polymer surface were separated by siloxane chains of specified length in order to achieve optimum interaction with the substrate and polymer viscosity. An example of great value for optical resolution is the polymer designated chirasil-Val, containing 0.86 mmole of iV-tert-butyl-L-valin-amide per gram of polymer (Fig. 5.14). 

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