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Solvent use consistently accounts for between 80 and 90% of mass utilization in a typical pharmaceutical/fine chemicals (non-polymer) batch chemical operation. Moreover, within these operations, solvents play a dominant role in the overall toxicity profile of any given process; i.e. on a mass basis, solvents account for the largest proportion of chemicals of concern used in the process. However, for the typical synthetic organic chemist, solvents are just a medium in which a reaction takes place; the interest is in the reactivity and building of a molecule, not in the means by which this is carried out. So, in a typical retrosynthetic analysis, solvent and solvent-reactant interactions, separability, and particle engineering are generally not included. The best means in which this reaction can take place is also not considered; i.e., the reaction space, configuration, order of addition, heat/mass transfer, etc., is generally not considered. This publication presents a case for greater awareness of solvent issues in batch chemical operations typically found in the pharmaceutical industry.
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Organic Process Research & Development
GlaxoSmithKline (United Kingdom)
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Constable et al. (Thu,) studied this question.