Background: Earlier, we developed a rapid procedure for the Leuckart reaction and successfully applied it for the synthesis of substituted N-ethyl-(1-phenylethyl)formamides. Specifically, the reaction between 2,4-dichloroacetophenone and N-ethylformamide was completed in 120 minutes. Recently, we extended our investigation to acetylpyridines and showed that the reaction between 2-acetylpyridine and N-ethylformamide can be completed even faster, in 20 minutes. Hypothesis: Chlorine is a moderately electron-withdrawing group. It reduces the electron density on the carbonyl and makes it more reactive towards N-ethylformamide. Consequently, the combined electron withdrawing action of two chlorine atoms and the nitrogen atom in 2-acetyl-3,5-dichloropyridine should result in a faster reaction with N-ethylformamide compared to the reaction of 2-acetylpyridine. Methods: The reaction was conducted on a 10 mmol scale at 180 - 199°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 30 minutes. The isolated yield of N-[1-(3,5-dichloropyridin-2-yl)ethyl]-N-ethylformamide was 92%. Conclusion: The results of the reaction contradict the initial hypothesis. The results could be explained by suggesting that the electron-withdrawing action of the nitrogen atom in 2-acetylpyridine is enhanced by protonation. Chlorine reduces the protonation by reducing the electron density on the nitrogen, thus making the reaction slower. 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.