Preferred Solvent for Synthesizing a Compound that can be Reversibly Extracted into Water.

 

Suppose I were presented with the problem of synthesising an organic compound that can be reversibly extracted into water at some pH (ie, an acid or base). Further, suppose that there is no powerful reason to use a particular solvent for the transformation, but I do know the plant reactor in which the reaction will likely be run in. What would my dream solvent be?

I know the minimum storable volume of the proposed reactor and the maximum volume of the reactor. So I would use a two-component solvent made up of o-dichlorobenzene and hexane. The ratio of hexane to o-dichlorobenzene would be (1/2 maximum volume - minimum stirrable volume) ÷ Minimum stirrable volume. 

Why o-dichlorobenzene? I want to be able to use enough o-dischlorobenzene to fully occupy the minimum storable volume in case it is necessary at some point to distil away all the hexane. Also, o-dichlorobenzene has a density of 1.31, so it will constitute the lower phase if I need to do a liquid-liquid extraction after distilling away hexane. Also, o-dichlorobenzene has a boiling point of 180 C, so it can serve as a chaser if I need to distil away any other solvents with significantly lower boiling points.

Why hexane? Hexane will ensure that the reaction temperature cannot, without resistance, go above 68.7 °C, the boiling point of hexane. I do not know what the optimal reaction temperature will be. A hydrocarbon cosolvent gives me the greatest number of very similar alternatives with different boiling points, which can serve as alternate stable reaction temperatures. Why the particular hexane: o-dichlorobenzene ratio? When I scale up, I want the o-dichlorobenzene to fill the minimum storable volume, while the reactor itself will be only half-filled in case I need to add more volume or perhaps an aqueous layer.

Hexane would be no more than my first choice for the second component of the solvent mixture, however, because any, preferably but not mandatory, water-immiscible solvent that can be distilled away from o-dichlorobenzene might function. I use a mixture of cosolvents because that makes the solvent composition adjustable during optimisation, knowing that waste solvents in the pharmaceutical and fine chemicals businesses are rarely recovered. 

The essential elements of this methodology for making a water-extractable product are (i) to use one cosolvent with a density greater than water and a boiling point distinctly different from that of the second solvent, and in a volume sufficient to occupy the minimum stirrable volume of the planned full-scale reactor and (ii) a final solvent that is immiscible with water.

The plan would be to conduct the chemical conversion at the best time-temperature combination studied. Then, optionally distil away the hexane, and add a water phase at the preferred pH to extract the desired product. Then drain away the lower chlorobenzene layer that contains any organically neutral & soluble co-products, byproducts, reagents or starting materials through the reactor’s bottom valve. Subsequently, any lighter than water organic solvent immiscible with water can be added into the reactor, and after adjusting the pH appropriately, the product will switch back into this upper organic layer, and the water can be drained off to waste. The product will remain partially worked-up, potentially in a solvent from which it can be crystallised or precipitated!