The formation of carbonyl compounds in electronic cigarette (e-cigarette) aerosols from thermal decomposition processes has been well established in the literature. These thermal decomposition products are thought to originate from the primary e-liquid components: propylene glycol (PG) and glycerin (GLY). The presence of specific α-dicarbonyl compounds has also been reported in e-cigarette aerosols. The α-dicarbonyl compounds of interest include glyoxal, methylglyoxal, 2,3-butanedione (diacetyl) , and 2,3-pentanedione (acetyl propionyl). The formation of these compounds is not readily explainable through typical dehydration and auto-oxidation pathways. The objective of this work is to develop an understanding of the potential reaction pathways for the formation of these compounds. A derivatization method using o-phenylenediamine was used to study the formation of the α-dicarbonyl compounds in e-liquids. To this end, a model reaction system that simulates a potential reaction environment of an e-cigarette atomizer was developed using a microwave reaction system. The effect of the e-liquid components (PG, GLY, nicotine, water, and flavors), reaction temperature, and time on α-dicarbonyl formation were determined. The implication of these results on potential reaction pathways for the formation of α-dicarbonyl compounds in the e-cigarette aerosolization process will be discussed.