Presentation: 2025 ND EPSCoR Annual conference 

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

Rapid synthesis of N-methyl-N-[1-(4-pyrimidinyl)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-methyl-(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 30 to 50 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 2-acetylpyrazine, which showed that the reaction can be completed even faster, in 15 and 9 minutes, respectively. Hypothesis: 4-acetylpyrimidine and 2-acetylpyrazine are close analogs. The 1,3-position of nitrogen atoms in the pyrimidine ring may provide even stronger electron-withdrawing action compared to the 1,4-position in the pyrazine ring. The stronger electron-withdrawing action should make the adjacent carbonyl more electrophilic, resulting in a faster reaction. Consequently, the reaction with 4-acetylpyrimidine should proceed faster than the reactions with 2-acetylpyrazine. Methods: The reaction was conducted on a 10 mmol scale at 180°C - 186°C. Extraction and column chromatography were used for the isolation of the product. NMR-spectroscopy and elemental analysis were used to determine the structure of the product. Result: The reaction was completed in 5 minutes. Conclusion: The results of the reaction support the initial hypothesis. The reaction time of 4-acetylpyrimidine was faster than the reaction time of 2-acetylpyrazine. N-methyl-N-[1-(4-pyrimidinyl)ethyl]-formamide is a new compound. Support: Research presented in this presentation was supported by the National Science Foundation under NSF EPSCoR Track-1 Cooperative Agreement OIA #1946202.