Catalyst-Free Gas-Phase Aldol Condensation in a GC–MS Inlet: In Situ Formation of Pyrones, Spirotriones, and β-Diketones

Gas chromatography–mass spectrometry (GC–MS) is traditionally employed for the detection and analysis of volatile compounds, yet it also offers a unique opportunity to probe gas-phase chemical reactivity. In this study, we report the in situ formation of three carbonyl-containing frameworks—6-acetyl-7-hydroxy-4H-chromen-5-one, 8-methyl-7-oxaspiro[4.5]dec-8-ene-1,6,10-trione, and 1-(2-oxocyclopentyl)-1,3-butanedione—via uncatalyzed aldol condensation reactions occurring at 360 °C within the GC–MS inlet. These products represent structurally diverse classes including pyrone derivatives, spirocyclic triones, and β-diketones, which are of broad interest due to their applications as fluorophores, pharmacophores, fragrance molecules, metal chelators, and synthetic intermediates. The GC–MS platform enabled not only compound separation and molecular ion identification but also real-time observation of condensation intermediates. Beyond their synthetic relevance, pyrones and related compounds are integral to natural product chemistry, pharmaceutical development, and environmental processes. This work underscores the dual functionality of GC–MS as both an analytical and discovery tool, offering new insights into catalyst-free condensation mechanisms in the gas phase.