The synthesis of a series of N-[3-(4-methylphenyl)-3-oxo-1-arylpropyl]acetamides using trifluoroacetic acid (TFA) as the catalyst was reported in this paper. It was achieved by a modified Dakin-West reaction using 4-methylacetophenone, aromatic aldehydes and acetonitrile as starting materials. The highest yield was up to 95% among the twenty eight target compounds synthesized. All the new compounds were characterized by ¹H NMR, ¹³C NMR and HRMS spectra. This one-pot reaction offered several advantages including small catalyst loading (0.3 mol%), moderate reaction temperatures (28～35 ℃) and simple post treatment procedure. A reaction mechanism was for the first time established, in which hydroxybenzaldehyde was first catalytically converted into corresponding acetoxybenzaldehyde prior to be involved in the subsequent Dakin-West reaction that eventually led to hydroxyl acetylated target compounds. The resultant hydroxyl acetylated β-acetamido ketones were selectively deacetylated in LiOH to produce the corresponding hydroxyl products with excellent yields. The current work further demonstrated that TFA was an efficient catalyst for Dakin-West reaction involving arylalkyl ketones, aromatic aldehydes and acetonitrile, which expanded significantly the scope of the substrates and provided a new synthetic route to β-acetamido ketones.

Key words: Dakin-West reaction, multi-component reaction, trifluoroacetic acid, β-acetamido ketone, 4-methylacetophenone, aromatic aldehyde