Presentation: 2025 ND EPSCoR Annual conference 

October 21, 2025, NDSU Memorial Union, Fargo, North Dakota

Rapid synthesis of N-[1-(2-pyrazinyl)ethyl]formamide

Background: Earlier, we developed a rapid procedure for the Leuckart reaction and successfully applied it for the synthesis of a series of substituted N-(1-phenylethyl)formamides. Depending on the type of the substituent on the benzene ring of the starting acetophenone, most of the reactions were completed in 10 to 20 minutes, much faster than the traditional Leuckart reaction that is usually completed within 3 to 6 hours. Recently, we extended our investigation to acetylpyridines and showed that the reaction can be completed even faster, in 5-10 minutes. Hypothesis: Acetylpyrazine is a close analog of acetylpyridines. The second nitrogen atom in the pyrazine ring works similar to an electron-withdrawing substituent. The electron-withdrawing action should make the adjacent carbonyl more electrophilic, resulting in a faster reaction. Consequently, the reaction with acetylpyrazine should proceed faster than the reactions with acetylpyridines. In this work the hypothesis was tested in the reaction between 2-acetylpyrazine and formamide. Methods: The reaction was conducted on a 10 mmol scale at 180°C. Extraction and column chromatography were used for the isolation of the product of the reaction. NMR spectroscopy and elemental analysis were used to determine the structure of the product. Result: The reaction was completed in less than 1 minute. The isolated yield of N-[1-(2-pyrazinyl)ethyl]formamide was 48%. Conclusion: The results of the reaction support the initial hypothesis. The reaction with 2-acetylpyrazine was completed nearly instantly, much faster than the reaction with 2-acetylpyridine that was completed in 5 minutes. Support: Research presented in this presentation was supported by the NSF under NSF EPSCoR Track-1 Cooperative Agreement OIA #1946202.