Solvents in organic synthesis: Replacement and multi-step reaction systems
Section snippets
Introduction and background
Solvents are widely used as reaction media in chemical, fine chemical and pharmaceutical industries, but they present numerous environmental, health and safety (EHS) challenges that need to be managed and are subject to increasing regulatory scrutiny. The above issues, amongst others, highlight the need to minimize and optimize the use of organic solvents as much as possible, as stated in the green chemistry principles (Anastas & Warner, 1998).
There is increasing and ongoing research into
Solvent selection methodology
The solvent selection methodology developed earlier by Gani et al. (2005) has been extended to handle multi-step chemical syntheses as well as solvent substitution for specific reaction steps in existing processes. The latter option has been receiving increased attention as more and more solvents in current use are being identified as having a series of environmental, health and safety challenges and therefore, “greener” substitutes are required. The new extended methodology consists of a
Computer-aided tools
A number of computer-aided methods and tools are needed. All the calculations discussed above can be performed through the integrated computer-aided system, ICAS (ICAS Documentation, 2003). A list of feasible solvent candidates satisfying all the desired property constraints can be generated through the search engine of the CAPEC database and/or through ICAS-ProCAMD, which is a toolbox for computer-aided molecular design. ICAS has been used because all the necessary methods and tools are
Case studies
The solvent selection methodology described above is evaluated through the application to three case studies. The first involves a problem reported earlier by Damstrup et al. (2005) involving the selection of solvents for efficient enzymatic monoacylglycerol production based on a glycerolysis reaction. This case study serves as a comparative assessment of the published results and the results obtained using the solvent selection methodology. The other two case studies involve the selection of
Conclusions
In this paper it has been shown that the methodology of Gani et al. (2005) can be successfully applied to single reactions, multi-stage reaction systems and problems of solvent replacement in order to obtain a preliminary list of potential solvent candidates.
For a single reaction case study, the results obtained are in accord with the results previously reported in the literature (Damstrup et al., 2005).
It was also possible to use this methodology to generate a list of potential solvents for
Acknowledgements
The authors wish to acknowledge Alan Curzons and Richard Henderson for their insights in the reactivity and chemistry and GSK R&D for providing some of the reactions for the case study. Financial support to Dr. Folić through the EU PRISM Project (MRTN-CT-2004-512233) is gratefully acknowledged.
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