Β-Keto Aldehyde Sodium Salt: A Useful but Unstable Solid

KiloMentor has stressed the selection of chemical routes of synthesis that pass through intermediates that are filterable solids, or even better, crystallizable salts. The most preferred salts are quite stable and can be both isolated and stored. Still, there are intermediates that are easy to isolate and are thus useful for separation and/or purification but are not sufficiently stable to store. That is, their separation is a phase switch useful for purification, but the product is not something that can be drummed off or otherwise accumulated but must be converted to another substance soon after formation. β-keto aldehyde sodium salts are of this type. They are usually prepared by reaction of a standard ketone with ethyl formate using sodium ethoxide or sodium hydride as base. The sodium salts sometimes fall out of the solvent or more often can be precipitated by the addition of a low polarity solvent such as diethyl ether. An example is provided in Organic Synthesis Coll. Vol. V pg. 187 where 2-methyl cyclohexanone is treated with ethyl formate and sodium ethoxide in diethyl ether. After 12 hours stirring the solid was filtered while protecting from oxygen and moisture in the atmosphere. It would seem possible to produce such a salt more quickly in an insoluble form if the reaction between the ketone and ethyl formate were conducted in a solvent less-polar than ethanol using sodium hydride as both the source of sodium ions and the reservoir of base, with just a catalytic amount of ethanol providing the sodium ethoxide that attacks the ketone to generate enolate. 

There are likely other general classes of solid intermediates that can be precipitated, for phase switching purposes, but that are not sufficiently stable to store as intermediates.