Updated methodology and scoring of the sustainability credentials of a total of 154 solvents, including 44 new additions.

No abstract

Solvent use consistently accounts for between 80 and 90% of mass utilization in a typical pharmaceutical/fine chemicals (nonpolymer) 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.

Reagent guides ranking commonly used reagents for 15 transformations have been developed to reduce the environmental impact of drug discovery and development. Reagents have been scored by a combination of health, safety and environmental risk phrases, life cycle analysis (where possible) and an assessment of the chemistry including considerations of atom efficiency, stoichiometry, work-up and other issues. Guides covering alkene reduction, amide formation, C-H bromination, C-H chlorination, deoxychlorination, epoxidation, ester formation, ether formation, fluorination, iodination, ketone reduction, nitro reduction, oxidation of alcohols to aldehydes and ketones, reductive amination and sulfur oxidation are shared, with an explanation of the methodology behind their generation. † Electronic supplementary information (ESI) available. See

Common acids and bases were ranked based on their EHS profile and the impact of their use in typical reactions.