Presentation: 2025 ND EPSCoR Annual conference 

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

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

Background: Recently, 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 substituent on the benzene ring of the starting acetophenone, most of the reactions were completed in 10 to 20 minutes, which is much faster than the traditional Leuckart reaction that is usually 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 on the benzene ring; this electron-withdrawing action should make the adjacent carbonyl more electrophilic, resulting in a faster reaction. Thus, the reaction time of acetylpyridines should be close to that of acetophenones with electron-withdrawing substituents. In this work, the hypothesis was tested in the reaction between 4-acetylpyridine and formamide. Methods: The reaction was conducted on a 10 mmol scale at 180-189°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 2 minutes. The isolated yield N-[1-(4-pyridyl)ethyl]formamide was 67%. Conclusion: The results of the reaction support the initial hypothesis. The reaction time of 4-acetylpyridene was faster than to the reaction time of 4-nitroacetophenone, the fastest reaction among the substituted acetophenones. 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 NIGMS and by the NSF under NSF EPSCoR Track-1 Cooperative Agreement OIA #1946202.