Preparation of labelled 2‐methoxy‐3‐alkylpyrazines: synthesis and characterization of deuterated 2‐methoxy‐3‐isopropylyrazine and 2‐methoxy‐3‐isobutylpyrazine

Abstract

SummaryEfficient synthetic routes for a number of deuterated analogues of 2-methoxy-3-isopropylpyrazines and 2-methoxy-3-isobutylpyrazines have been developed involving the condensation of glyoxal with an a-amino acid amide followed by methylation with iodomethane. In this way [

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

“…However, the products obtained showed different gas chromatographic (GC) properties compared with reference MPs 4a-c. This paper clarifies some of the previously published results and summarizes the chromatographic and spectroscopic characterization of compounds obtained by the method described by Gerritsma et al 16 and MPs, respectively their deuterated isotopologues.…”

“…In our hands, the deuterated derivatives obtained after the approach of Gerritsma et al 16 ( Figure 1, route C) were not the designated MPs d 3 -4a-c, as they showed considerably higher retention indices after GC analysis, than those for the commercial non-deuterated MP reference substances. We obtained substances, which could later be assigned to the structures of d 3 -3a-c. Incorporation of deuterium into an organic molecule leads to a somewhat lowered retention index in gas liquid chromatography, despite its higher absolute molecular mass.…”

“…To verify synthesis procedures, deuterated sec-butyl pyrazine derivative was synthesized according to the originally described pathway ( Figure 1, route A; d 3 -4b) as well as the non-deuterated compound (later assigned as 3b) according to Gerritsma et al 16 ( Figure 1, route C). GC and GC-MS data of the compound obtained from route A are consistent with those of the reference compound SBMP 4b from Sigma-Aldrich (Table S-1).…”

“…The reason for this result was supposed to be that hydroxypyrazines 1 exist largely in the pyrazinone 1 Ã form in neutral solution, which could be confirmed by IR 14 or NMR 15 experiments. In a more recent publication, Gerritsma et al 16 described a method using sodium hydride and iodomethane to convert the originally formed hydroxypyrazines 1 to the targeted 2-methoxy-3-alkylpyrazines 4 ( Figure 1, route C; later ascertained as a misconception, since this route leads to compounds 3 as outlined below). These authors also described the synthesis of the deuterated isotopologues (using [ following the approach of stable isotope dilution analysis (SIDA) for quantification.…”

“…17 In the work described here, we synthesized the desired deuterated 2-[ 2 H 3 ]methoxy-3-alkylpyrazines d 3 -4a-c for wine aroma analysis. Considering the published methods described for MP synthesis, we first followed the method described by Gerritsma et al 16 ( Figure 1, route C) as it seemed to be the most convenient approach. However, the products obtained showed different gas chromatographic (GC) properties compared with reference MPs 4a-c.…”