ACS Green Chemistry Institute®

Driving Green Solvent Selection

Blog Post created by ACS Green Chemistry Institute® on Jul 5, 2018

By Louis Diorazio, Pharmaceutical Technology and Development, AstraZeneca

 

Solvents are commonplace chemicals across industry and academia.  In many cases, the bulk of the materials that chemists process are solvents with the ‘interesting stuff’ present only as minor components.  From this, it can be seen that the greenness of a chemical process, whether in a lab or a manufacturing plant, will be heavily influenced by the selection of the correct solvent.  Although solvents can offer green credentials in their own right, this only translates into a green process once we recognize that the purpose of a solvent is to effectively support an application such as synthesis, coating or formulation.  A green solvent may not provide for a green process if we don’t properly consider its influence on aspects of the application from the molecular to the macro scale such as:

 

  • Accessible temperature window
  • ‘Molecular’ properties  and interactions e.g. pKa, redox potential, metal binding, solubility
  • Side reactions and impurities
  • Available analytical technologies e.g. refractive index, spectral properties
  • Product isolation and drying

 

Effective solvent selection should progress beyond the current contents of the solvent cupboard or from a limited appraisal of options.  The principles of solvent selection are very simple and start with a straightforward challenge ‘Do I really need a solvent?’  In many applications (e.g. making low cost / high volume materials), solvents bring unnecessary dilution and no benefit but if the need for a solvent can be justified, there are only two additional questions to answer:

 

  1. What properties do I need from a solvent?
  2. What solvents fulfill those requirements?

 

The new Solvent Selection Tool launched publicly by the ACS Green Chemistry Institute Pharmaceutical Roundtable sets out to provide answers to these questions. Users start from a pool of 272 solvents that can be filtered based on a wide range of criteria such as:

 

  • Chemical functionality
  • Physical properties
  • Engineering and plant accommodation
  • Safety Health and Environment
  • ICH classification

 

In this way, the user can address traditional processing concerns such as chemical reactivity or water miscibility alongside environmental considerations. The tool deliberately avoids explicitly identifying solvent identities until the user is happy with the size of their shortlist, all of which fulfills the set criteria. Some unconventional or unexpected options may be encountered, the key is to be open to change – after all, what does a solvent look like? Ultimately this provides for rational solvent selection where results can be explored directly in lab studies or refined using predictive methods.

 

The issue of solvent selection is becoming more critical as legislation places restrictions on some traditional solvents (e.g. glyme, HMPA, benzene, NMP, DME) for reasons of health or environmental impact. This challenge will only increase over time and scientists will need to be more open minded with respect to solvent choice in the future.

 

Our perspective should focus on green solvent selection, i.e. providing end-to-end performance against all criteria rather than force-fitting a green solvent and expecting an optimal result. Take a look at the tool and tell us what you think.

 

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L.J.Diorazio, D.R.J.Hose, N.K.Adlington, Org. Process Res. Dev., 2016, 20, 760-773

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