Title:A Mild and Eco-friendly, One-pot Synthesis of 2-hydroxy-Narylacetamides
from 2-chloro-N-arylacetamides
Volume: 21
Issue: 5
Author(s): Vamshikrishna Y. Radhakrishna, Gopal L. Khatik, Bhuvaneshwari S. Vijaya and Vipin A. Nair*
Affiliation:
- Department of Chemistry, REVA University, Yelahanka, Bangalore, 560064, Karnataka, India
Keywords:
2-Hydroxy-N-arylacetamides, diisopropyl ethylamine, copper (II) acetate, nucleophilic substitution, 2-chloro-narylacetamides, potassium hydroxide.
Abstract: A mild and eco-friendly one-pot, two-step procedure has been developed for the synthesis
of 2-hydroxy-N-arylacetamides from 2-chloro-N-arylacetamides. The procedure overcomes the
cleavage of the amide linkage in 2-chloroacetamides, which is usually observed under reflux conditions
with the hydroxide when the nucleophilic substitution of the halide is attempted. The reactions
were performed by refluxing 2-chloro-N-arylacetamides with Cu(OAc)2 and DIPEA in the ethanol
medium to facilitate an acetate exchange with the halogen. Subsequently, by the addition of ethanolic
KOH solution to the same reaction flask, the ester linkage was selectively cleaved in the presence of
the amide, taking advantage of the difference in electrophilicity. The procedure afforded good yields
of the desired products, which are valuable intermediates for several biologically active molecules, in
a short reaction time with ease of isolation. The experimental conditions employed are simple and offer
the possibility of scaling up to higher quantities.
