Methyl Ethyl Ketone (2-Butanone) as a Uniquely Useful Solvent

Anhydrous Hydrochloride and Hydrobromide Salts

The reason that I write the blog KiloMentor is to pass along whatever ‘tricks of the trade’ I have picked up in my career doing organic synthesis. While I was Research Director and President at QuébéPharma Recherche Inc. in Montreal Canada, a consultant, Lars Svendsen, said in an aside to our discussions that methylethylketone (MEK, 2-butanone) was a particularly good solvent for making a hydrochloride or hydrobromide salt because the water could be removed by heating to distill the water azeotrope. 

The azeotrope between MEK and water boils at 73.4℃ and has 12% water in the distillate. Since MEK itself boils at 79.6℃ the temperature gap between it and the azeotrope will be sufficient that a distillation column will not be required to take off fairly uncontaminated azeotrope.

It is not clear whether this process of making the solution anhydrous is performed before or after adding the basic group that is to be formed into a salt. It would logically be more likely that the heating to distill the azeotropic composition would be done after the neutralization. Distilling first would likely drive off some of the volatile hydrogen chloride gas and could cause some degradation of the ketone solvent.

MEK/Water Liquid-Liquid Extractions

KiloMentor is always on the lookout for mixtures of two liquids that are not completely miscible but could partition similar solutes usefully between the two layers. This would make liquid-liquid partitioning a practicable separation method.  A mixture of methyl ethyl ketone and water might do that. I calculate that at 25℃, water will dissolve 18.2% of its weight of MEK while a MEK phase will dissolve 12.5% of its weight of water.

Other Useful Methyl Ethyl Ketone Azeotropes

Besides its behavior with water, MEK  forms lower boiling azeotropes with ethyl acetate (77℃/18% in distillate) and cyclohexane (71.8℃/40.0% in distillate).