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Issues Around the Use of Solvents

At the screening level, as broad a range of solvents as possible will be utilised to determine ideal conditions such as solubility, reaction temperature (as determined by boiling point), partition coefficient etc.[1]  The use of a full solvent set will indicate which classes of solubilising agents give best results and what solvent properties dominate the solvent effects. 

However, researchers should be aware of solvents that have been categorised as highly hazardous or worse and their use should be avoided even during screening reactions.  The highly hazardous classifications can be due to health, safety or environmental reasons as well as regulatory constraints.  In their editorial policy, the journal Organic Process Research and Development discourages research conducted using ‘strongly undesirable solvents’ such as benzene, carbon tetrachloride, chloroform, HMPA, carbon disulphide.

Solvents that fall into this category include [2]:

  • Carcinogenic solvents e.g. benzene, 1,2-dichloroethane (H350).
  • Ozone depleting solvents e.g. Carbon tetrachloride (H420).
  • Chloroform, due to its toxicity.
  • Diethyl ether, due to the safety risks associated with its low flash point; low boiling point; resistivity; ability to form peroxides and low auto-ignition temperature.
  • Nitromethane, due to its high energy of decomposition.

Dipolar aprotic solvents are another class of solvents that are subject to an increasing amount of scrutiny. N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAc) and 1-Methyl-2-pyrrolidone (NMP) have all been named as substances of very high concern (SVHC) on the REACH Candidate list for Authorisation

As with all chemicals, solvents and their use are subject to legislation; for further study, see Environmental Legislation in the Process Design topic.  

  1. R. C. McElroy, A. Constantinou, L. C. Jones, L. Summerton and J. H. Clark, Towards a holistic approach to metrics for the 21st century pharmaceutical industry, Green Chem., 2015, 17, 3111-3121.
  2. D. Prat, J. Hayler and A. Wells, A survey of solvent selection guides, Green Chem., 2014, 16, 4546-4551.