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Efficient One-Pot Microwave-Assisted Synthesis, Crystallographic, and Spectroscopic Characterization of Novel Antitumor and Antimicrobial (3E)-5-Hydroxy-1Isopropyl-3-[(5-Methyl-2-Thienyl)Methylene]-5-Phenylpyrrolidin-2-One
Abstract
A microwave-assisted, chemoselective synthesis of novel antitumor and antimicrobial (3E)-5-hydroxy-1-isopropyl-3-[(5-methyl-2-thienyl)methylene]-5-phenylpyrrolidin-2-one has been achieved via the solvent-free one-pot reaction of (3E)-3-[(5-methyl-2-thienyl)methylene]-5-phenylfuran-2(3H)-one with isopropylamine. The product is obtained in significant purity and yield under ecofriendly reaction conditions. The microwave technique surpasses conventional thermal heating approaches by accelerating the reaction in a clean, ecofriendly manner that avoids the use of organic or toxic solvents. The structural formula of the product is confirmed by crystallographic and spectroscopic characterization. X-ray single crystal diffraction reveals that the compound crystallizes in an orthorhombic centrosymmetric crystal form, with unambiguous assignment of the E-configuration for the C3-Cthienyl bond. The synthesized molecules have two centers of chirality in the hydroxypyrrolidin-2-one ring: 1) the carbon atom attached to nitrogen, the hydroxyl group, and the phenyl ring; 2) the nitrogen atom attached to the carbonyl carbon R3 group, the chiral carbon in the ring, and the covalent bond bearing the lone pair of electrons. The molecular geometry is also optimized using density functional theory calculations, and the results obtained are in good agreement with the experimental data. Evaluation of the biological and medicinal activity of the compound affords similar results to the reference data in antitumor treatment of human colon and breast cells, which can be attributed to the presence of the hydroxyl group, the heterocyclic motifs, and sulfur. Calculation of the molecular electrostatic potential locates the most electrophilic site near the hydroxyl group attached to the heterocyclic ring, which is consistent with the bioactivity results. The frontier molecular orbitals are also determined, finding that the energy difference between highest occupied molecular orbital and lowest unoccupied molecular orbital is -0.15228 eV. A mechanism is proposed in which an intramolecular nucleophilic attack occurs on the carbonyl carbon by the lone pair of electrons on the nitrogen atom, leading to ring closure with proton transfer to oxygen and final formation of the hydroxyl group.
Keywords
microwave,
chemoselective,
hydroxypyrrolidin-2-one,
catalyst- and solvent-free,
ecofriendly,
crystallographic characterization
Supporting agencies: We thank Dr. El Sayed Shalaby (Elettra-Sincrotrone Trieste, Italy & Crystallography Lab., NRC, Egypt) for the great help during X-ray diffraction data collection and crystal structure refinement. We thank Dr. Shadia M. Abdallah, Associate professor of Organic Chemistry, Department of Chemistry, Faculty of Women for Arts, Science, and Education, Ain Shams University, Cairo, Egypt, for her great help during this work
About the Authors
E. M. Azmy
Department of Chemistry at Ain Shams University
Egypt
Egypt
Heliopolis, Cairo
B. M. Awad
Department of Chemistry at Ain Shams University
Egypt
Egypt
Heliopolis, Cairo
H. A. Hefni
Department of Chemistry at Ain Shams University
Egypt
Egypt
Heliopolis, Cairo
H. A. Saad
Department of Chemistry at Ain Shams University
Egypt
Egypt
Heliopolis, Cairo
A. M. Eltoukhya
Department of Chemistry at Ain Shams University
Egypt
Egypt
Heliopolis, Cairo
А. F. Mabied
X-Ray Crystallography Lab., Solid State Physics Department, National Research Center; Department of Basic Sciences, October High Institute of Engineering & Technology-OHI
Egypt
Egypt
Dokki, Giza
M. S. M. A. El-Kareem
Molecular and Atomic Physics unit., Experimental Nuclear Physics Department, Nuclear Research Center, Egyptian Atomic Energy Authority
Egypt
Egypt
Inshas, Cairo
N. Demitri
Elettra Sincrotrone Trieste
Italy
Italy
34149 Basovizza-Trieste
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Review
For citations:
Azmy E.M., Awad B.M., Hefni H.A., Saad H.A., Eltoukhya A.M., Mabied А.F., El-Kareem M., Demitri N. Efficient One-Pot Microwave-Assisted Synthesis, Crystallographic, and Spectroscopic Characterization of Novel Antitumor and Antimicrobial (3E)-5-Hydroxy-1Isopropyl-3-[(5-Methyl-2-Thienyl)Methylene]-5-Phenylpyrrolidin-2-One. Zhurnal Prikladnoii Spektroskopii. 2021;88(2):334(1)-334(10).
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