Presentation: 2025 ND EPSCoR Annual conference 

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

Rapid synthesis of N-ethyl-N-[1-(4-pyridyl)ethyl]formamide

ABSTRACT Background: Earlier, we developed a rapid procedure for the Leuckart reaction and successfully applied it for the synthesis of a series of substituted N-ethyl-(1-phenylethyl)formamides. Depending on the type of substituent on the benzene ring of the starting acetophenone, most of the reactions were completed in 30 to 60 minutes, much faster than the traditional Leuckart reaction, typically completed within 3 to 6 hours. Hypothesis: Acetylpyridines are close analogs of acetophenones. The nitrogen atom in the pyridine ring works similarly to an electron-withdrawing substituent in the benzene ring. The electron-withdrawing action should make the adjacent carbonyl more electrophilic, resulting in a faster reaction. Consequently, the reaction time of acetylpyridines should be similar to acetophenones with electron-withdrawing substituents.The hypothesis was tested in the reaction between 4-acetylpyridine and N-ethylformamide. Methods: The reaction was conducted on a 5 mmol scale at 180ºC - 191ºC. Extraction and column chromatography were used for product isolation. NMR-spectroscopy and elemental analysis were used to determine the product's structure. Result: The reaction was completed in 15 minutes. Isolated yield of N-ethyl-N-[1-(4-pyridyl)ethyl]formamide was 64%. Conclusion: The results support the initial hypothesis. The reaction time of 4-acetylpyridine was faster than the fastest reaction among the substituted acetophenones. N-ethyl-N-[1-(4-pyridyl)ethyl]formamide is a new compound. Support: Research presented in this presentation was supported by NIH grant 8 P20 GM103442-12 from the National Institute of General Medical Sciences and by the National Science Foundation under NSF EPSCoR Track-1 Cooperative Agreement OIA #1946202.