Pyridine-Water Selective Precipitation with Pyridine Recovery

 

Dissolution of a solute in a water-miscible solvent followed by crystallization or precipitation of the solute by gradual or portion-wise addition of water is an established method of separation and purification.  It is frequently applied to the separation of mixtures of different polymers.

 Solvents commonly used are methanol or ethanol. When lower alcohols are used with small molecule substrates it amounts to the same thing or at least strongly resembles crystallization from mixed alcohol-water solvent. When more expensive organic liquids are used as solvents to be practical at scale there must exist a cheap straightforward method to recover that solvent.

Pyridine is miscible with water in all proportions. It can be used to purify solutes or separate mixtures of solutes by the gradual addition of water so as to cause fractional precipitation. Typically one starts with something like a mixture of 5 parts pyridine and 1 part solute which can be warmed to dissolve what may be a solid or oily mixture; then, one gradually adds water with vigorous stirring until faint turbidity persists. At this point, optionally, a small amount of pyridine (a drop or two at the laboratory scale) can be added to just clear the haziness. Crystallization may begin after some time. In Aleksandra Smoczkiewiczowa and Jan Bielawny's paper in  P. Zakresu Towarozn. Chem.,Wysza Szk. Ekon. Poznaniu, Zesz. Nauk., Ser. 1 1970 No. 36, 149-62, it says that their cholesterol oxidation mixture was dissolved in a 5-fold amount of pyridine and by addition of water fractionally precipitated about 15% androstenolone acetate.

 Pyridine is somewhat expensive as solvents go. No obvious simple means to recover the pyridine when the precipitation is complete makes this an infrequently used methodology  Pure pyridine cannot be recovered by distillation because pyridine/water forms an azeotrope. Fortunately, there is a technical trick that does achieve this separation. Pyridine is not particularly soluble when sodium hydroxide is dissolved into the aqueous pyridine so the addition of enough caustic causes pyridine-water to separate into two phases. The pyridine layer can be separated and the mostly- layer discarded.