Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

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.

Synthesis and structural determination of some 1,5-disubstituted-4-ethoxycarbonyl-3-hydroxy-3-pyrroline-2-one derivatives containing nitro group

“…The initial step in MCRs to synthesize 1,5-disubstituted-4-ethoxycarbonyl-3-hydroxy-3-pyrroline-2-ones (4a-c) takes place via the reaction between substituted benzaldehyde (1a-c) and 4-nitroaniline (2a) to yield imine (5) [27] (Figure 4). Therefore, the presence of substituent groups attached to the benzene ring in the structure of starting materials will affect both the rate and the yield of imine formation reaction [10].…”

“…Nitro group (NO2), an electron-withdrawing group, in 4-nitroaniline (2a) results in the decrease in the nucleophilicity of the amino group (-NH2) [28]. Therefore, the imine formation reaction rate between benzaldehyde (1a) and 4-nitroaniline (2a) is slower than that between benzaldehyde (1a) and aniline [27], [29]. Consequently, there was a dramatic decrease in the yield of 1-(4-nitrophenyl)-5-phenyl-4-ethoxycarbonyl-3-hydroxy-3-pyrroline-2-one (4a), 38% (Table 1), as compared to the synthesis of 1,5-diphenyl-4-ethoxycarbonyl-3-hydroxy-3pyrroline-2-one, 86% [10].…”

“…The formation of the imine between 1b and 2a is slower than that between 1a and 2a, and consequently, the yield of 4b is lower than that of 4a. In contrast, the presence of nitro group (NO2) in reactant 1c leads to the increase in the electrophilicity of the carbonyl carbon atom [27], [28], [29]. As a consequence, the yield of 4c is higher than that of 4a and 4b (Table 1).…”