Solvent Selection Methodology Department Editor: Rita L. D’Aquino Chemical Engineering®

Organic solvents have been used in many industries for centuries, but the methods and tools to select optimal solvents while minimizing their adverse environmental, health, safety and operational concerns are still evolving. The appropriate selection of solvents depends to a large extent on the application, more specifically on what needs to be dissolved, and under what conditions. This article presents a four-step approach to solvent selection based upon Ref. 1^* , where the reader will find a list of additional resources on this topic.

Identify the challenge and solvent characteristics
The first two steps are:
1) identifying the actual problem and technology or unit operation required to solve it; and
2) defining the requirements that must be met by the solvent, using criteria related to its physical and chemical properties (e.g., pure-solvent properties, such as normal boiling point, the Hildebrand solubility parameter at 300 K, the Hansen solubility parameters; solventsolute properties, such as the solubility of the solute as a function of the composition of the mixture; and functional constraints, such as solute loss in solute).

Obtain reliable values of solvent properties and narrow down selection
There are several alternatives for this third step. For example, one can measure the required properties, use a database of properties of chemicals (or solvents), or, use property models to estimate them. For solvent-selection problems not involving chemical reactions, the pattern of the desired solvent is established through analysis of the solute, application type, and other constraints.

Once this is established, a database of known solvents can be used to identify the solvents that match the necessary pattern (Table 1). On the other hand, when chemical reactions are
involved, the approach is based on transition-state theory and requires consideration of the solvation energies of the reactants, products and transition states, and thus, knowledge of the reaction mechanism.

When the crucial values have been found, the solvent search
could be such that first, solvent-pure properties are used, followed by solvent-EHS, then solvent-solute, and finally solvent-function.

Narrow down the list by removing the compounds that do not match desired properties. A protocol derived by Britest Ltd. (www.britest.co.uk) seeks to use mechanistic principles to guide solvent selection (Figure). The objective is to follow the arrows according to the problem definition and a search criterion until an end-point is reached, thereby obtaining the characteristics of the candidate solvents. These characteristics are used to identify the group to which the solvents belong using solvents database (see Table 2). The corresponding
group-types are evaluated and a final selection is made.

Verify selection
The fourth step is to verify that the solvent works as expected by performing a computational validation by simulation. Experimental validation of a solvent candidate is required at all stages of process development.