264-275 LCE May05ready

Recently, the subject of “green chemistry” has received considerable attention from academic and industrial researchers alike.1 While the central tenets of waste reduction, process economy and elimination of risks and hazards have long been embraced by industrial process chemists, the current focus on green chemistry concerns has led to renewed appreciation for the importance of these topics. The analysis of the “greenness” of any given process, operation or methodology is a useful exercise that can lead to process improvement and refinements. This exercise can be particularly valuable for new technologies that might not yet have a long track record of practical utilization. Preparative chromatographic resolution of enantiomers is one such emerging technology that has recently become widely used for providing rapid access to enantiopure materials to support pharmaceutical development. Here we provide an overview of green chemistry issues relating to preparative chromatography, concentrating especially on the green advantages of preparative supercritical fluid chromatography (SFC), in which carbon dioxide replaces the flammable and toxic petrochemical-derived hydrocarbon solvents typically used in preparative liquid chromatography. Can Preparative Chromatography Be Green? First impressions might suggest that preparative chromatography, with its intensive use of solvent, is decidedly “un-green.” However, economic factors usually dictate that industrial-scale chromatographic processes employ solvent recycling.2 In addition, the smaller scale preparative chromatography performed in support of developmental research can sometimes eliminate the need for developing and performing more traditional chemical syntheses, thereby saving considerable labour and time,3 and sometimes even resulting in a net decrease in waste generation. Thus, the use of preparative chromatography can sometimes be a “greener” approach to conventional development. Furthermore, newer forms of preparative chromatography, such as SFC, can be viewed as an even greener alternative to classic preparative chromatography. (Please see the sidebar that follows.)