Interesting Solvent Possibilities: Ternary Thermomorphic Azeotropes that Break upon Cooling into Two Similar Volumes of Liquids

Warning: 

The author is unaware of any examples of reactions running in either of the proposed thermomorphic solvent systems. Neither is he aware of any work-ups, purifications, or product isolations performed using the two phases into which these azeotropic compositions separate on cooling. 

Testing these ideas would make an excellent undergraduate research project for a college student majoring in organic chemistry. Furthermore, the result if positive would be publishable!

Introduction

Using thermomorphic phases to try, by liquid-liquid extraction, to separate a mixture of very similar compounds may have advantages compared with trying the same technique using more typical pairs of poorly miscible liquids because the thermomorphic phases would likely be more similar to each other than two ordinary immiscible solvents and so offer a better chance to display significantly different partition ratios even for quite small differences between solute components.

Thermomorphic solvent systems provide two distinct liquid phases within a first temperature range and a single homogeneous liquid phase within a second different range. 

Using the upper and lower phases from a thermomorphic azeotropic composition, first as a reaction solvent and subsequently, as the two immiscible liquids of a counter-current extractive separation might be simple and convenient. It would seem that the ratio of volumes of the two phases needs to be conserved in all the liquid-liquid extractions that are attempted. Otherwise, the two phases will cease being immiscible. Also, the proportion of solvents to substrates must be kept relatively large so that the substrates do not disturb the proportions of solvents distributed between the two thermomorphic phases. 

 There is reason to believe that a complex organic substrate with both hydrophilic and hydrophobic segments will be more soluble in a mixed solvent made up of more and less hydrophilic constituents. This would suggest that a thermomorphic liquid would be a better reaction solvent for such a substrate than most pure solvents. Thus the thermomorphic mixture could be a good choice for the initial chemical reaction part of a process step.

In the work-up part, the reactor contents would be cooled down to the temperature range where two liquid phases appear; the layers would be physically moved into different vessels and each liquid reextracted with the correct volume of the other immiscible thermomorphic phase. The separation would proceed in exactly the same fashion as a standard counter-current extraction with the added proviso that the correct ratio of volumes of the two immiscible phases be maintained in every extraction

Finally, the composition in the separate portions from the counter-current process is analyzed and the pure fractions are combined and concentrated.

In the laboratory version of this technique, each separate phase can be vacuum evaporated to dryness and redissolved in hot thermomorphic single-phase and cooled down to separate.

 Two inexpensive thermomorphic solvent systems that separate into comparable volumes of two immiscible phases are provided below.

  Ethanol/Toluene/Water Ternary Azeotrope

One such composition is an azeotropic mixture of ethanol, toluene, and water boiling at 74.4 C, which has a composition of 37.0% ethanol, 51.0% toluene, and 12.0% water. 

The distillate from it separates into two immiscible liquids with the upper layer composition having a 15.6% ethanol, 81.3% toluene, and 3.1% water composition and a specific gravity of 0.849.  This upper phase constitutes 46.5% by volume of the distillate. 

The lower phase of specific gravity 0.855, consists of 53.5% of the total volume and is 54.8% ethanol, 24.5 % toluene, and 20.7% water. The low difference in specific gravities between the two immiscible phases suggests that the phase separation may be slow.

Whether this will be a difficulty will need to be investigated.

Ethanol/Heptane/Water Ternary Azeotrope

A mixture of ethanol, heptane, and water forms a ternary azeotrope boiling at 68.8 C which has a composition of 33.0% ethanol, 60.9% heptane, and 6.1% water. The distillate separates into two immiscible liquids with the upper layer composition being 5.0% ethanol, 94.8% heptane, and 0.2% water. The specific gravity of the upper phase is 0.686.  The upper phase constitutes 64.6% by volume of the distillate. The lower phase of density 0.801 constituting 35.4% of the total volume, is 75.9% ethanol, 9.1% heptane, and 15.0% water.

Another ternary thermomorphic combination is isopropanol/toluene/water.