The Advantages of Ethanol-Cyclohexane Mixtures as Organic Reaction Solvent Media

In designing process steps for fine chemical synthesis a bias has existed against multi-component solvent systems. In the past, it was argued that using combinations of solvents meant that money would be lost because it would be necessary to separate these solvents in a recovery step. What was not then properly recognized was that recovery of solvents from mixtures for reuse was rarely undertaken in the fine chemical and pharmaceutical industries mainly because recovering and recycling solvents required extensive expensive analytical work to prove that the specifications were being consistently met.

Here I will look at combinations of cyclohexane and absolute ethanol.

There are contradictory teachings in the literature concerning the miscibility or immiscibility of ethanol and cyclohexane. This confusion may be because the UCST (upper critical solution temperature ) of the combination is reported to be -16℃. In the laboratory, it is difficult to maintain the contents of a separatory funnel at any temperature less than 0℃  but this should be much less a problem in the plant where extractions are conducted in a reactor completely surrounded by a heating/cooling jacket and the entire charge is maintained throughout under inert gas. Therefore, one could predict that two phases might not be seen in the laboratory but would be reasonably easily achieved with the more readily accessible plant peripherals.

Ethanol and cyclohexane do have an azeotrope ( bp 64.9℃ ) that boils significantly below the boiling point of either pure ethanol ( bp 78.5℃ ) or pure cyclohexane ( bp 81.4℃ ). Mixtures in any proportion of these two pure liquids will give a homogeneous reaction medium above -16℃ and fractional distillation of the reaction mixture will remove the azeotropic composition and leave the non-volatile substrates in either ethanol or cyclohexane depending upon what solvent predominated in the starting mix.

Alternatively, the reaction mixture can be cooled to below -16℃ to see whether or not two liquid phases separate and if so how the substrates of interest partition between them. It needs to be noted however that even if two liquid phases separate that separation may be slow since they are expected to have close to the same densities. A small addition of water may cause separation in cases where nothing is apparently happening.

As you can see, this binary solvent mixture provides options in the work-up and isolation.