A Facile and Efficient One-Pot Procedure for the Synthesis of Novel 2-Substituted 3-Thioxoisoindolin-1-one Derivatives
Fatemeh Gholami, Ali Moazzam, Saeed Bahadorikhalili, Mehdi Adib*, Samanesadat Hosseini, Bagher Larijani, Mohammad Mahdavi*
*School of Chemistry, College of Science, University of Tehran, Tehran; Tehran University of Medical Sciences, Tehran 11174, Iran
Email: madibkhayam.ut.ac.ir, momahdavi
sina.tums.ac.ir
F. Gholami, A. Moazzam, S. Bahadorikhalili, M. Adib, S. Hosseini, B. Larijani, M. Mahdavi, Synlett, 2022, 33, 1729-1732.
DOI: 10.1055/a-1912-2293
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Abstract
An efficient synthesis of 2-substituted 3-thioxoisoindolin-1-one derivatives is based on the solvent-free reaction of 2-carboxybenzaldehyde with aliphatic amines and sulfur at 100°C. This reaction enables a facile synthesis of asymmetric thioxoisoindolin-1-one derivatives with phthalimide backbones.
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Details
This paper presents a novel and efficient one-pot method for synthesizing 2-substituted 3-thioxoisoindolin-1-one derivatives. The method involves a solvent-free reaction of 2-carboxy-benzaldehyde with aliphatic amines and sulfur at 100°C. This synthesis is significant for pharmaceutical applications due to the facile production of asymmetric thioxoisoindolin-1-one derivatives with phthalimide backbones, which are known for their broad pharmaceutical activities, including antimicrobial, anticonvulsant, antihistaminic, anti-inflammatory, and hypolipidemic properties. The study highlights the limitations of traditional reagents like Lawesson’s reagent, which cannot selectively react with one carbonyl group in compounds containing multiple carbonyl groups. The optimized reaction conditions involve using neat conditions at 100°C for 3 hours, yielding the desired products in good yields. The scope of the reaction was tested with various aliphatic amines, resulting in moderate to good yields of the novel derivatives. The proposed mechanism involves the formation of intermediates through condensation, proton transfer, and nucleophilic attack steps. This method opens new avenues for synthesizing asymmetrically substituted phthalimide derivatives, potentially enhancing their biological activities. The research was supported by the University of Tehran, and the authors declare no conflict of interest.
Key Words
benzo-fused N-heterocycles, phthalimides, multicomponent reactions
ID: J72-Y2022