Trifluoroacetic Acid–Catalyzed Synthesis of N-(1-(3-Chlorophenyl)-3-aryl-3-oxopropyl)-2-(4-nitrophenyl)acetamides via Dakin–West Reaction

Abstract

A series of novel N-(1-(3-chlorophenyl)-3-aryl-3-oxopropyl)-2-(4-nitrophenyl) acetamides were synthesized using p-nitrophenylacetonitrile, m-chlorobenzaldehyde, and aryl methyl ketones as starting materials and trifluoroacetic acid (TFA) as catalyst. This realized an improved Dakin–West reaction in which p-nitrophenylacetonitrile was involved. The chemical structures of up to 15 target molecules were characterized by ¹H NMR, ¹³C NMR, and high-resolution mass spectrometry. This method provides a facile synthetic protocol under more moderate reaction conditions, smaller dosage (0.40 mol%) and hence lower cost of catalyst, and simpler posttreatment in comparison to other known methods. A reaction mechanism is proposed in which hydroxyacetophenone is first catalytically converted into the corresponding acetoxyacetophenone prior to be involved in the subsequent Dakin–West reaction that eventually leads to hydroxyl-acetylated target compounds.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]

GRAPHICAL ABSTRACT

Keywords:

• β-Arylacetamido ketone
• Dakin–West reaction
• multicomponent reaction
• p-nitrophenyl acetonitrile
• trifluoroacetic acid

ACKNOWLEDGMENTS

This project is supported by the National Natural Science Foundation of China (No. 21172181) and The Chongqing Science and Technology Research Project (2011AB5001, 2011AC1053). The authors are also grateful to Qunli Luo, Chengbin Gong, and Ning Wang for their assistance in measuring ¹H and ¹³C NMR spectra.

Notes

^a The reactions were performed in CH₂Cl₂ at 35 °C for 24 h, aided by AcCl (0.4 mL), and in the following amounts: p-nitrophenylacetonitrile, 0.5 mmol; m-chlorobenzaldehyde, 0.6 mmol, and acetophenone, 0.6 mmol.

^b Isolated yield based on p-nitrophenylacetonitrile.

^a The reactions were performed with the following amounts: p-nitrophenylacetonitrile, 1.0 mmol, m-chlorobenzaldehyde, 1.2 mmol; and aryl methyl ketones, 1.2 mmol.

^b At 45 °C.

^c At 35 °C.