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.

Propylene Carbonate as a Useful Solvent for Organic Synthesis Processes

The density of propylene carbonate is 1.189 g/cc and the dielectric constant and dipole moment respectively are 64.94 and 16.5.  It is a solvent that can be expected to provide good solubility for a wide range of organic reaction substrates.

Propylene carbonate may be the only solvent that is (a) usefully immiscible with water, (b) does not contain a halogen in its formula, yet (c) has a density greater than water. At 25°C the solubility of propylene carbonate in water is 8.3% and the solubility of water in propylene carbonate is 17.5%. Excess water forms a second phase on top of the water-saturated propylene carbonate. When the mixture of liquids is cooled to near 0° C the separation of phases is even greater. Thus, propylene carbonate can provide two phases that can be used for liquid-liquid extractions. Moreover, the more predominantly organic layer is the lower phase and in a reactor can be simply cut through the bottom valve. Thus, when the product can be taken into the aqueous phase by acid or base, the organic phase can be removed leaving the product in the reactor. This can save a vessel in a chemical process work-up.

 In fact, propylene carbonate is thermotropic with appropriate water mixtures. As the temperature is varied between 0 and 61°C, the two phases that derive from a particular weight fraction of propylene carbonate and water, change compositions. It would therefore be expected that the partitioning of a mixture of substrates, such as might be the products from a reaction step,  could be optimized between the two phases both by varying the propylene carbonate/water weight fraction and by changing the temperature of the two-phase mixture. The UCST for propylene carbonate and water is about 72 C. At this temperature, only a single distinct clear phase remains. 

Propylene carbonate can be hydrolyzed by both aqueous acid and aqueous base. There is both a good and a bad aspect to this. The bad is that the stability of the solvent in contact with water is 

somewhat limited. This, however, is also true of ethyl acetate where it is not regarded as a severe limitation. The good part is that small amounts of the solvent mixed with a hydrolytically stable cosolvent can be removed by hydrolysis since the products, carbon dioxide and propylene glycol are both water-soluble.