Solvents and Process efficiency

Solvent Selection:

Solvents are a key area of focus for organic chemists looking to improve the greenness of their processes as they are usually the largest mass input of a synthetic process or transformation.

A comprehensive tool for evaluating a solvent or potential alternative is the ACS GCIPR interactive solvent guide (depicted below). This tool allows permits interactive solvent selection based upon the Principal Component Analysis (PCA) of the solvent’s physical properties. Solvents which are close to each other in the map have similar physical and chemical properties, whereas distant solvents are significantly different. In addition, other data including the physical poperties, functional groups, and environmental data has been included to aid nthe rational selection of solvents. This tool is further defined in "Toward a More Holistic Framework for Solvent Selection". Diorazio, L. J.; Hose, D. R. J.; Adlington, N. K., Org. Process Res. Dev. 2016, 20, 760-773.


Solvent Literature:


The solvent selection tool screenshot.


Reagent Selection:

Selecting the most sustainable reagent to use for organic chemistry transformations requires the assessment of many factors including atom efficiency, toxicology, safety, waste products, sustainable feedstocks, and more. Industrial multidisciplinary chemists, as members of the ACS GCIPR, have compiled reagent guides to inform and assist organic chemists in the selection of reagents for >19 transformations or procedures.

Each guide, in the collection of guides, is a comprehensive resource composed of:

Referneces:


An abstract ven diagram of attributes of the ideal reagent. An detailed ven diagram of attributes of the ideal reagent.


Biocatalysis guide:

Biocatalysis is a key green technology for modern sustainable organic syntheses. The Biocatalysis Guide is a simple double-sided, single-sheet guide to the currently most used enzyme classes amongst the ACS GCI member companies. It has been produced to be an easy-to-follow guide for chemists who have not had significant exposure to biocatalysis, showing generic transformations that are available so these can be factored into retrosynthetic analysis.

The top row of the biocatalysis guide PDF from the GCIPR.


Med Chem:

All parts of pharmaceutical development can be made more sustainable. A great example of this is the ACS GCIPR Medicinal Chemistry Team’s approaches to greening medicinal chemistry. The team produced this quick guide covering purification, solvent selection, reagents, energy and resources.


Process Mass Intensity:

Process mass intensity (PMI) is the key green mass-based metric for measuring the resource usage impact of a synthetic chemistry process.

$$PMI = \frac{Mass of Raw Materials Input}{Mass of Product}$$
The PMI calculator enables organic chemists to quickly determine the PMI number from the raw material inputs and final product yield. The calculator accommodates multi-step convergent syntheses and includes breakdown of solvent, reagents, and water PMI. These calculations are an invaluable method to drive development of more sustainable processes and to track the mass efficiency for a synthetic procedure.Process mass intensity data has been gathered to provide benchmarking data for the small-molecule, oligonucleotide, peptide, and monoclonal antibody therapeutic classes.

References:

The PMI prediction tool (depicted below) provides a simple and accessible means of predicting the mass efficiency of proposed synthetic routes. The tool is built from a dataset of nearly two thousand multi-kilo reactions provided by pharmaceutical, biotech, and manufacturing ompanies via the ACS GCIPR as well as extracted from the literature. By defining a sequence of reactions and their corresponding reaction type, it is possible to estimate a plausible PMI for ay proposed or unoptimized organic chemistry route. This ability to virtually screen different rspective routes for efficiency allows organic chemists to focus their resources on a few poising synthetic approaches.
This process is elaborated in "The PMI Predictor app to enable green-by-design chemical synthesis". Borovika, A.; Albrecht, J.; Li, J.; Wells, A. S.; Briddell, C.; Dillon, B. R.; Diorazio, L. J.; Gage, J. R.; Gallou, F.; Koenig, S. G.; Kopach, M. E.; Leahy, D. K.; Martinez, I.; Olbrich, M.; Piper, J. L.; Roschangar, F.; Sherer, E. C.; Eastgate, M. D. Nature Sustainability. 2019 , 2, 1034–1040

A representative screenshot of the PMI tool.


Green Chemistry Innovation Scorecard Calculator:

Green Chemistry Innovation Scorecard Calculator is a slightly different approach to accounting for PMI by focusing on waste. A joint effort by the IQ Consortium, ACS GCI Pharmaceutical Roundtable, and academic leaders, this Green Chemistry Innovation Scorecard web calculator illustrates how green chemistry and engineering innovation can reduce waste mass during bulk active pharmaceutical manufacture. The calculator uses a statistical analysis of 64 bulk active pharmaceutical manufacturing processes encompassing 703 steps across 12 companies to provide a relative process greenness score. This score may then be used as a means of making meaningful comparisons between different processes and their associated waste reductions.

References:

Green Chemistry Innovation Scorecard Calculator:

Green Chemistry Innovation Scorecard Calculator is a slightly different approach to accounting for PMI by focusing on waste. A joint effort by the IQ Consortium, ACS GCI Pharmaceutical Roundtable, and academic leaders, this Green Chemistry Innovation Scorecard web calculator illustrates how green chemistry and engineering innovation can reduce waste mass during bulk active pharmaceutical manufacture. The calculator uses a statistical analysis of 64 bulk active pharmaceutical manufacturing processes encompassing 703 steps across 12 companies to provide a relative process greenness score. This score may then be used as a means of making meaningful comparisons between different processes and their associated waste reductions.

References:

General Resources: