Preparative scale supercritical fluid chromatography

Villeneuve, M.S., and Miller, L.A. (2005) Preparative-scale supercritical fluid chromatography, in Preparative Enantioselective Chromatography, 1st edn (ed. G.B. Cox), Wiley-Blackwell,... 

Hochlowski, J. Searle, P. Gunawardana, G. Sowin, T Pan, J. Olson, J. Trumbull, J. Development and Application of a Preparative Scale Supercritical Fluid Chromatography System for High Throughput Purification, presented at Prep 2001, Washington, DC, May, 2001. 

Hochlowski J, Sauer D, Sowin T. Preparative scale supercritical fluid chromatography in support of HTOS. Presented at High Throughput Organic Synthesis. San Diego, CA, February 2002. 

Hochlowski J, Searle P, Gunawardana G, Sowin T, Pan J, Olson J, Trumbull J. Development and application of a preparative scale supercritical fluid chromatography system for high throughput purification. Presented at Prep 2001. Washington, DC, 2001. 

Preparative chromatography can be practised on two different scales laboratory (recovery of grams of sample) and production (recovery of kilograms of sample). Preparative Scale Supercritical Fluid Chromatography (PS-SFC) has been practised on the laboratory scale from the very beginning of SFC in 1962 [1], More information on these historical experiments has been gathered by Berger et al. [2] and Bevan [3]. 

Packed-column SFC also is suitable for preparative-scale enatioseparations. Compared with preparative LC, sub- or supercritical fluid chromatography results in easier product and solvent recovery, reduced solvent waste and cost, and higher output per unit time. Because of its reduced sample capacity, SFC usually allows the separation of 10-100 mg samples per run. Chromatographers can compensate for these sample amounts by using shorter analysis times and repetitive injections (Wolf and Pirkle, 1997). 

The coated polysaccharide-based phases have mostly been used in normal phase conditions, but an increasing number of preparative applications have been reported in supercritical fluid chromatography [33] or reversed phase mode [34]. The broad applicability of the coated polysaccharide-based CSPs has made them very popular and they are now widely used for preparative separation of enantiomers and large-scale applications up to tonnes per year have been reported [35, 36]. The success of these CSPs is documented in numerous papers and these CSPs are the most used phases for analytical and preparative applications. 

Supercritical fluid chromatography (SFC) uses supercritical gases as a mobile phase [14-17]. The solvent power of supercritical gases is determined by density (see above) which can be easily modified by pressure [18]. Furthermore, separation of the eluted compounds is easily achieved by pressure release. Liquid solvents may be only applied in minor quantities as modiflers. Therefore, SFC has good potential for scale-up to preparative and production scale chromatography [15-17,19,20]. 

The sorption applications include regeneration of porous beds, preparative scale supercritical chromatography, simulated moving beds, thermal swing schemes, and adsorp-tion/desorptions cycles. Although initial applications of supercritical fluids in this domain were on regeneration of porous beds, more recent emphasis on fractionation best reflects... 

SUPERCRITICAL FLUID CHROMATOGRAPHY (SFC) ON A PREPARATIVE AND PRODUCTION SCALE... 

Supercritical fluid chromatography (SFC) has been employed at the analytical scale by a number of workers for several years [1]. Scaling-up the technique for preparative use has been investigated and developed by relatively few and still presents a number of challenges. 

It is beyond the scope of this chapter to review the extensive literature available for the use of analytical supercritical fluid chromatography and extraction. However it is important for the reader to appreciate the problems posed by scaling-up the ana-l)dical technique for preparative and process scale applications. 

In order to overcome this lack of selectivity, photodimerizations have been performed in micelles,16,17 in supercritical fluids,18 in inclusion compounds19 and in the solid state.20 Nevertheless, such reactions are difficult to run on a preparative scale, and better results can be obtained by careful choice of an appropriate solvent. Enantioselcctive gas chromatography combined with GC/MS analysis proved to be a very efficient tool for the direct assignment of constitution and configuration of the photocyclodimers formed.21 In this manner, /ram-1,2-di-vinylcyclobutane has been prepared by sensitized irradiation of buta-1,3-diene.22... 

Analytical systems do equip almost all laboratories. Many different kinds of particle sizes are used from 20 to 2 [tm (from HPLC to UPLC), using liquid or supercritical fluid mobile phases. An intermediate market is to be considered using 10 mm ID columns for small-scale purifications. The term preparative chromatography is dedicated to purification units using column diameters from 50 up to 1600 mm ID. 

This Chapter relates the problems associated with scaling-up the technique for use at the laboratory preparative level and above and pays special attention to the technical demands on materials and apparatus to ensure complete safety in the operation of the chromatograph. The ideas and designs of others will be reviewed and compared with the authors own approach. The advantages and disadvantages offered by the various systems will be explained in sufficient detail for the reader to adopt the system most suited to his/her needs. The non-specialist reader may not be familiar with the use of supercritical fluids as mobile phases in chromatography so the Chapter is introduced with a brief explanation of the nature of the supercritical state. 

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