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

Nguyen Tran Nguyen; Vo Viet Dai; Nguyen Ngoc Tri; Luc Van Meervelt; Nguyen Tien Trung; Wim Dehaen

doi:10.3762/bjoc.18.118

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

Beilstein J Org Chem. 2022 Aug 31:18:1140-1153. doi: 10.3762/bjoc.18.118. eCollection 2022.

Authors

Nguyen Tran Nguyen¹, Vo Viet Dai¹, Nguyen Ngoc Tri², Luc Van Meervelt³, Nguyen Tien Trung², Wim Dehaen⁴

Affiliations

¹ Department of Chemistry, University of Science and Education, the University of Da Nang, Ton Duc Thang 459, 550000 Da Nang, Viet Nam.
² Laboratory of Computational Chemistry and Modelling, Faculty of Natural Sciences, Quy Nhon University, An Duong Vuong 170, 820000 Quy Nhon, Viet Nam.
³ Biomolecular Architecture, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, B-3001 Leuven, Belgium.
⁴ Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, B-3001 Leuven, Belgium.

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.

Keywords: 1,5-dihydro-2H-pyrrol-2-ones; 2-pyrrolidinone derivative; 3-pyrroline-2-one; 4-acetyl-3-hydroxy-3-pyrroline-2-ones; pyrrolidine-2,3-dione.

Grants and funding

This research was financially supported by Ministry of Education and Training, Vietnam (project grant B2021-DNA-17).