ABSTRACT
Substituted 4-acetyl-3-hydroxy-3-pyrroline-2-ones have been prepared via three-component reactions and the tautomerism of these 3-pyrroline-2-ones is due to the slight difference of energy, and the significantly large rate constant of transformation between two tautomers. 1,4,5-Trisubstituted pyrrolidine-2,3-dione derivatives were prepared from the above mentioned 2-pyrrolidinone derivatives and aliphatic amines, which exist in enamine form and are stabilized by an intramolecular hydrogen bond. A possible reaction mechanism between 3-pyrroline-2-one and aliphatic amine (CH3NH2) was proposed based on computational results and the main product is formed favorably following the PES via the lowest ΔG # pathway in both the gas-phase and an ethanol solvent model. DFT calculations showed that kinetic selectivity is more significant than thermodynamic selectivity for forming main products.
ABSTRACT
The heterocyclic γ-lactam ring 2-pyrrolidinone has four carbon atoms and one nitrogen atom. Among the group of derivatives of 2-pyrrolidinones, 1,5-dihydro-2H-pyrrol-2-ones, also known as 3-pyrroline-2-ones, play a significant structural role in a variety of bioactive natural compounds. In this study, three-component reactions were used to successfully synthesize six polysubstituted 3-hydroxy-3-pyrroline-2-one derivatives. The antioxidant activity of the compounds was tested by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, identifying 4-ethoxycarbonyl-3-hydroxy-5-(4-methylphenyl)-1-phenyl-3-pyrroline-2-one (4b) as the most promising radical scavenger. Quantum chemistry calculations of the thermodynamics and kinetics of the radical scavenging activity also suggest that 4b is an effective HOË radical scavenger, with k overall values of 2.05 × 109 and 1.54 × 1010 M-1 s-1 in pentyl ethanoate and water, respectively. On the other hand, 4b could not scavenge hydroperoxyl radicals in either media. The ability of 4b to scavenge hydroxyl radicals in polar and non-polar environments is comparable to that of conventional antioxidants such as melatonin, gallic acid, indole-3-carbinol, ramalin, or Trolox. Thus 4b may be classed as a promising HOË radical scavenger in the physiological environment.