Catalyst-Free Gas-Phase Synthesis of Pyrones via Thermally Induced Aldol Condensation of Acetoacetate Derivatives Using GC–MS

Traditional pyrone syntheses typically require catalysts, solvents, or high pressures, limiting their sustainability. Here, we report the first catalyst-free, solvent-free gas-phase synthesis of substituted pyrones using gas chromatography–mass spectrometry (GC–MS) as both a reaction platform and analytical tool. Direct injection of methyl, ethyl, propyl, isopropyl, and tert-butyl acetoacetates into the heated GC inlet under optimized thermal conditions produced 3-acetyl-4-hydroxy-6-methyl-2H-pyran-2-one as the dominant product, along with a homologous series of alkyl 4,6-dimethyl-2-oxo-2H-pyran-5-carboxylates. Electron-impact ionization mass spectrometry (EI–MS) confirmed product structures based on characteristic fragment ions and incremental mass shifts (m/z 182–224) consistent with alkyl chain extension. The consistent formation of 2,4,6-heptanetrione supports a parallel cleavage pathway. Temperature-dependent studies revealed that pyrone formation is a thermally activated, self-condensation process that proceeds entirely in the gas phase. Mechanistic analysis suggests the formation of reactive acylium and ketene intermediates that undergo aldol condensation followed by cyclization or transesterification. This work provides the first experimental evidence of gas-phase aldol condensation of β-keto esters, demonstrating a simplified and greener synthetic route to oxygen heterocycles and establishing GC–MS as a powerful microscale platform for probing thermal organic transformations.