Deuterium Exchange in Ethyl Acetoacetate: An Undergraduate GC–MS Experiment

Abstract

A simple experiment involving deuterium exchange of the enolizable protons in ethyl acetoacetate followed by GC–MS has been developed. The principles demonstrated are the use of stable isotopes, keto–enol tautomerism, base catalysis, and the use of specific reagents to minimize or nullify side reactions. The changes in mass of specific fragment ions, as well as that of the molecular ions are indicative of the course of the reaction and illustrative of the fragmentation pathways. The acidity of the methylene hydrogens of the acetoacetate moiety is exploited in the acetoacetic ester synthesis of alkyl-substituted acetones. These readily exchange under very mild conditions. More challenging is to exchange all five enolizable hydrogens. Use of increasingly severe reaction conditions leads to side reactions, such as deuterolysis of the ester portion if D2O is used. The solution was to use ethanol O–d as the source of deuterium and KOD for the base for the exchange reaction and moderate heat. The role of ethanol O–d in nullifying the deuterolysis is demonstrated by determining that trans-esterification of methyl acetoacetate to the ethyl ester occurs as well as deuterium exchange of the five acetoacetate hydrogens.