New insights into the synthesis and characterization of 2‐methoxy‐3‐alkylpyrazines and their deuterated isotopologues

A previously described synthetic route for preparation of 2‐methoxy‐3‐alkylprazines (MPs) based on condensation of glyoxal with an α ‐amino acid amide, followed by methylation with iodomethane yields 3‐alkyl‐1‐methyl‐1H‐pyrazin‐2‐ones ( N ‐methyl derivatives), rather than the designated 2‐methoxy‐3‐alkylpyrazines ( O ‐methyl derivatives). Despite similar nuclear magnetic resonance and mass spectral properties, gas chromatographic (GC) retention indices differ significantly, indicating chemical difference. With the example of 3‐sec‐butyl‐1‐methyl‐1H‐pyrazin‐2‐one and its 3‐sec‐butyl‐1‐[ 2 H 3 ]methyl‐1H‐pyrazin‐2‐one isotopologue, the position of the methyl group introduced could be assigned unambiguously, using heteronuclear multiple bond correlation (HMBC) NMR experiments. For future characterization, the spectroscopic (NMR, EI + MS) as well as GC retention index data on two stationary phases of the most aroma relevant MPs and their deuterated isotopologues are summarized. Copyright © 2011 John Wiley & Sons, Ltd.