Synthesis of N-[1-(4-bromophenyl)ethyl]-N-ethylformamide

Background: Earlier, we developed a rapid procedure for the Leuckart reaction and successfully applied it for synthesis of substituted N-(1-phenylethyl)formamides. Specifically, the reaction between 4-bromoacetophenone and formamide was completed in 15 minutes, producing N-[1-(4-bromophenyl)ethyl]formamide with isolated yield of 75%. The new procedure appeared to be much faster than the traditional Leuckart reaction, usually completed within 3-6 hours. Later, we conducted the reaction between 4-bromoacetophenone and N-methylformamide. The reaction appeared to be slower, completed in 75 minutes. This indicated that the size of the substituent attached to the nitrogen atom of formamide plays the major role in determining the rate of the reaction. Hypothesis: Since the ethyl group in N-ethylformamide is larger than the methyl in N-methylformamide, the reaction between 4-bromoacetophenone and N-ethylformamide will proceed slower than the reaction between 4-bromoacetophenone and N-methylformamide. Methods: The reaction was conducted on a 5mmol scale at 180-209℃. Extraction and column chromatography were used for isolation of the product. NMR-spectroscopy and elemental analysis were used to determine the structure. Result: The reaction was completed in 100 minutes and produced N-[1-(4-bromophenyl)ethyl]-N-ethylformamide. Conclusion: The results of the reaction support the initial hypothesis. The reaction provides a new method for the synthesis of N-[1-(4-bromophenyl)ethyl]-N-ethylformamide. N-[1-(4-bromophenyl)ethyl]-N-ethylformamide is a new compound. Support: This research 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.