Reactive Distillation using Enamine Formation for Separating Different Ketones also useful for Separating Ketones from non-Ketones

Two ketones with different steric surroundings, when caused to react with an insufficient quantity of an appropriately selected cyclic secondary amine, will have different rates of formation and different equilibrium concentrations of enamines.

For example, according to Peter W. Hickmott in Tetrahedron 38, 1975 (1982), a mixture of non-, mono-, and di-methylated 4-t-butyl-cyclohexanone was separated by first allowing the mixture of ketones in refluxing benzene to react with gradually increasing amounts of morpholine until gas chromatographic analysis indicated that all of the non-methylated fraction had disappeared owing to the formation of its examine. Then the unreacted ketones were removed and treated with increasing amounts of the more reactive amine pyrrolidine until gas chromatography show all of the monomethylated compounds had disappeared by forming enamines. The dimethylated ketone could then be distilled off and separation was complete!

A small steric or molecular weight difference is magnified into something that allows simple separation.

It should be obvious that the same methodology in a simpler form could be applied to separating a mixture of ketones and non-ketones. The ketone fraction would be derivatized with an appropriately reactive cyclic secondary amine, the catalyst neutralized and the fraction (not changed in properties) separated. The ketone fraction could be converted back from enamine by acid-catalyzed hydrolysis and the secondary amine taken into acidic water.