(583a) Towards More Sustainable Pharmaceutical Syntheses: Finding Solvent Replacements | AIChE

(583a) Towards More Sustainable Pharmaceutical Syntheses: Finding Solvent Replacements

Authors 

Jimenez-Gonzalez, C. - Presenter, North Carolina State University
Constable, D. - Presenter, GlaxoSmithKline


Solvents are widely used as reaction media in the chemical, fine chemical and pharmaceutical industries, but they present numerous environmental, health and safety challenges that need to be managed, including increasing regulatory scrutiny. These challenges, amongst others, highlight the need to avoid using organic solvents as much as possible. When organic solvents must be employed, their use must be minimised and optimised to enhance reactivity while minimizing environmental and operational concerns.

A method to select appropriate ?greener' solvents for the promotion of a class of organic reactions has been previously developed. The method employs estimates of thermodynamic properties to generate a knowledge base of reaction and solvent-related properties that directly or indirectly influence the rate and/or conversion of a given reaction. The methodology and main ideas are given in the paper ?Method for Selection of Solvents for Promotion of Organic Reactions? by Gani, Jiménez-González and Constable (Computers & Chemical Engineering, 2005).

This presentation covers the evaluation and application of this methodology and will present results covering two types of applications. The first application is an evaluation of suitable replacements for dichloromethane (DCM) as the solvent in two pharmaceutical reactions. A preliminary list of potential DCM replacement solvents was identified and these solvents would need to undergo further experimental evaluations before final selection of the most appropriate replacement could be made.

The second application looked at solvent selection across a multi-stage reaction system. The overall procedure was to formulate the solvent search parameters and generate the solvent candidates for each reaction stage followed by an evaluation of the candidates list to select a shorter list for further investigation. This multi-stage reaction case study was aimed at the selection of greener solvents from the overall process and process solvent rationalization perspective. A preliminary list of potentially suitable solvents for each reaction step was obtained that resulted in a matrix of solvents (rows) and reaction stages (columns). This matrix was used to identify those solvents that could be used for more than one reaction stage. Further experimental evaluations need to be performed for these solvents to identify the most appropriate set of solvents for the multi-stage reaction system.