A Trick for Working Up Reaction Mixtures Comprising Polar, Water-Soluble Organic Solvents

Suppose you have a neutral substrate contained in a polar organic solvent and would like to wash it with water to remove some reagent byproducts, but that solvent is miscible with water? Examples would be DMF, DMSO, THF, Dioxane, Isopropanol. Consider adding the water first to give a single phase, but then, into this mixture of the first two, add methyl acetate or ethyl formate. These lower esters are not particularly soluble in water so what will happen when it goes into this mixture? Most likely, two phases will separate; an organic phase comprising mostly the troublesome polar organic solvent ( ie DMF, DMSO, THF, Dioxane, Isopropanol ) along with the lower ester and a second phase which is predominantly water. Your organic reaction product will be substantially in the combined organic layer. A cut can be made.

This procedure is deemed to have the advantage that the two phases initially form as small droplets ensuring good contact between the phases. In regular extractions wherein the two immiscible liquids are mixed from bulk, in slow mass-transfer systems, high-intensity mixing is required. Such intense mixing can form fine dispersions which reduce the coalescence rate or, in the presence of surface-active impurities, may even cause a “stable emulsion”. This is one of the operating hazards of solvent extraction equipment. This order of mixing: the two miscible solvents first followed by the third which causes the phase separation is taught in US 5,628,905. Quoting from this publication, “The inherent advantage of this method is that it works effectively even in the presence of substances (solid or dispersed) that cause the formation of emulsions or stable dispersions.”

Distillation of this mixture should drive off the low molecular weight ester that was added as a processing chemical leaving the original organic solvent separated and washed clean!

Organic solvents such as ethyl acetate can be freed from small amounts of DMSO by washing with 5% sodium chloride in water. This trick was taught to me in 1997 by Jong Tao, then of Torcan Chemical Ltd..