Reaction of Ethyl 3-Aryl-2-cyanoacrylates with N,N-Disubstituted Malonamides: Synthesis and Properties of Stable Michael Adducts

Abstract

The reaction of ethyl 3-aryl-2-cyanoacrylates (arylmethylene cyanoacetates) with N1,N3-disubstituted malonamides in the presence of Et3N under mild conditions (absolute EtOH, 25°C) produces new stable Michael adducts, ethyl 3-aryl-2-cyano-5-oxo-5-(N-R-amino)-4-(N-R-carbamoyl)pentanoates, in 57–95% yields. The structure of the obtained compounds was confirmed by IR, 1H, 13C NMR spectroscopy, high-resolution mass spectrometry, and X-ray crystallography. The stereochemical features of the obtained Michael adducts have been studied. Calculations using the semi-empirical GFN2-xTB method showed that the cyclization of the obtained adducts is a thermodynamically favorable process but has a high energy barrier (~206 kJ/mol) and cannot occur under the reaction conditions. The antibacterial activity of a series of the obtained Michael adducts was studied.