2-Propylpyrazine

14508-49-7

2234-82-4

18138-03-9

The general procedure for the synthesis of 2-propylpyrazine from 2-chloropyrazine and propylmagnesium chloride was as follows: first, 8.0 mL of 2-chloropyrazine, 1.58 g of iron acetylacetonate (Fe(acac)3), and 100 mL of tetrahydrofuran (THF) were added to a stirred round-bottomed flask. The mixture was stirred under nitrogen protection to form a red solution. The flask was cooled in an ice water bath for 10 minutes. Subsequently, 49 mL of n-propylmagnesium chloride was slowly added and the solution turned dark purple. After 1.5 hours of reaction, an additional 10 mL of n-propylmagnesium chloride was added over 10 minutes. after 20 minutes, 5 mL of n-propylmagnesium chloride continued to be added. After stirring for about 30 minutes, 22 mL of saturated aqueous ammonium chloride (NH4Cl) was added over 7 minutes. After an additional 7 mL of NH4Cl was added, stirring was stopped and the mixture was allowed to stand at room temperature under nitrogen protection overnight. After addition of 125 mL of ethyl acetate (EtOAc) and 450 mL of water, the mixture was filtered through a polypropylene filter and transferred to a partition funnel. The organic and aqueous phases were separated and the aqueous phase was extracted twice with 125 mL of EtOAc. The organic phase was combined and filtered through Celite. Subsequently, it was concentrated using a rotary evaporator at 200 mbar and 40 °C. The fractions were purified by short-range distillation and Vigreux column distillation (200 mbar, 90-110 °C) to give 9.0 g (82.4% yield) of 2-n-propylpyrazine. The purity of the final product was confirmed by HPLC analysis using an Elipse XDB-C8 column (4.6 × 150 mm, 5 μm) with a mobile phase of 60:40 acetonitrile/water (containing 1% trifluoroacetic acid) at a flow rate of 1 mL/min, a column temperature of 35 °C, and a retention time of 3.0 minutes.