Synthesis of 3-alkyl oxazolidines, derived from 2-hydroxymethyl piperidine, as analytical standards for the analysis of volatile aldehydes in the workplace

Hexahydro-3-alkyl-3H-oxazolo[3,4-a]pyridines 4-15 for the quantitative analysis of various aldehydes were obtained in good yield via the condensation reaction of 2-hydroxymethylpiperidine (2-HMP) with aldehydes under mild conditions. When acrolein is used, the bicyclic 17 was obtained. This novel compound has suitable physical characteristic for an analytical standard. The hexahydro-3-vinyl-3H-oxazolo[3,4-a]pyridine 16 can be achieve at higher temperature. Using specific conditions, a diastereomeric mixture of 18/19 and pure 18, which are both bisadducts of 2-HMP with acrolein, can be obtained. Mechanistically, a thorough 1H-NMR study did not show any evidence that the condensation reaction proceeded via an enamine. The reaction probably proceeds through an elusive hemiaminal and fleeting iminium ion, which underwent subsequent cyclisation to gave hexahydro-3-alkyl-3H-oxazolo[3,4-a]pyridines 4-16. The reaction pathways for the preparation of 4-18 are described.