Elsevier

Computers & Chemical Engineering

Volume 32, Issue 10, 17 October 2008, Pages 2420-2444
Computers & Chemical Engineering

Solvents in organic synthesis: Replacement and multi-step reaction systems

https://doi.org/10.1016/j.compchemeng.2008.01.006Get rights and content

Abstract

The solvent selection methodology developed earlier by Gani et al. [Gani, R., Jiménez-González, C., & Constable, D. J. C. (2005). Method for selection of solvents for promotion of organic reactions. Computers and Chemical Engineering, 29, 1661–1676] has been extended to handle multi-step reaction systems as well as solvent substitution for specific reaction steps for existing processing systems. The problems were formulated based on the methodology guidelines, and solved using ICAS software tool [ICAS Documentation. (2003). Internal report. CAPEC, Department of Chemical Engineering, Technical University of Denmark]. Highly promising results were obtained, either in accordance with results previously published in the literature, or with industrial process data. This shows that the methodology has potential for application to complex reaction schemes as well as on the problems of solvent replacement.

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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