Why Use a Miscible Solvent Mixture?

Throughput

A solvent mixture may well dissolve more substrate than pure solvent. In fine chemicals synthesis where solvent is not recycled but sent for destruction there is no cost advantage from a single solvent but getting more substrate dissolved homogeneously in a reactor can improve the economics by increasing throughput, especially in early process steps which need to be run multiple times.

Increasing the Heat Capacity

The preferred solvent for yield optimization may be one that boils well above the best reaction temperature. Adding a co-solvent that boils at the desired reaction temperature can increase the heat capacity of the medium at the reaction temperature because the lower boiler’s vaporization into the condenser and the returning condensate will cool the reactor. Consequently, addition rates of reactants can be higher.

Changing a Phase’s Density

Some solvents are more dense, some less dense than water.  In work-ups with water, sometimes having the product containing liquid phase more and sometimes less dense than water has advantages. The number of large vessels needed to execute a process step may depend upon it. Fewer vessels mean less cleaning and a smaller burden on plant facilities.

Reducing the Solubility of a Product or Co-product

Decreasing the solubility of a product or co-product can cause it to precipitate as the reaction proceeds. This can drive an equilibrium towards completion and raise the overall yield.

Making Telescoping Reactions Easier

Sometimes it is not useful to isolate a process intermediate but the solvents appropriate for the present and subsequent process steps are not the same. A solvent switch is required. Evaporation to dryness is not possible at scale. It would be advantageous if the second step in the telescoped pair was optimized in a solvent mixture consisting of a minor amount of the first solvent and a majority of second solvent. If this were done it would not be required to substantially remove the first solvent. This might save substantial time.

Because the Solvent Mixture Selected is a Constant Boiling Azeotrope

A constant boiling azeotrope has a fixed composition and it boils at a constant boiling point. In these respects, it is the same as a pure single molecular species. It can usually be purified by simple distillation. However, many azeotropes have the advantage that by changing the pressure-usually by reducing the pressure- the azeotrope can be split into its component substances by distillation. This distillation at a different pressure can potentially remove the better solvent and lead to precipitation or crystallization of a solute.  

To Reduce Solvent Viscosity

Solvents that are viscous are often usefully high boiling but their viscosity is a problem for stirring and for heat conduction. Mixing with another solvent can reduce the viscosity of the reaction medium.

To Provide a Distillation Chaser

Adding a higher boiling solvent into a reaction solvent mixture ca provide a chaser for reaction mixtures that are subsequently worked-up by distillation. Sometimes a substantial amount of product is lost in the still pot and the distillation column. Of course, this chaser can also be added after the reaction is over but before the distillation step.

Drying Simplicity 

Drying solvents on scale with inorganic salts followed by filtration of the inorganic salt hydrates uses labour, equipment, and time inefficiently.  It is greatly disfavoured for work at scale. The preferred method for solvent drying selects a solvent that forms an azeotrope with water and distills a portion of the solvent as the azeotrope.

Raising the Freezing Point 

At what temperature does the solvent that is being considered solidify or become highly viscous? The freezing point can limit the range of temperatures that can be used in the optimization.  Lowering the temperature is often the best option for increasing the selectivity of a desired reaction versus competing reactions that produce by-products. If low temperatures create viscous reaction mixtures, these can result in hot-spots during reagent additions, inadequate mixing leading to incorrect stoichiometry, creating in turn by-products, and poor crystallization control. For example, DMSO when diluted with a small amount of toluene is more resistant to freezing and so can be cooled to a lower reaction temperature.