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Synthesis, regioselectivity, and DFT analysis of new antioxidant pyrazolo[4,3-c]quinoline-3,4-diones

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Abstract

The condensation of hydrazine, N-methylhydrazine, and N-phenylhydrazine with ethyl 4-chloro-2-oxo-1,2-dihydroquinoline-3-carboxylate derivatives has been investigated. As a result, 12 new antioxidant pyrazolo[4,3-c]quinolin-3,4-diones were obtained with good to high yields. When two cross-products could be possible, only one isomer bearing the methyl or the phenyl group at the N1 position is isolated and unequivocally characterized using 1D and 2D NMR techniques, FT-IR, and combustion analyses. DFT analysis of the reaction mechanism was carried out in the Pearson’s hard soft acid base framework, confirming the assigned structure to the observed pyrazolo[4,3-c]quinolin-3,4-diones. These calculations indicate a favored kinetic control for the synthesized pyrazolo[4,3-c]quinolin-3,4-diones compared to its possible regioisomer.

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Acknowledgments

The authors thank the Regional University Hospital of Besançon for support (France). Financial support from Regional Council of Franche-Comté (Besançon, France) is also acknowledged. Computations have been performed on the supercomputer facilities of the Mésocentre de calcul de Franche-Comté (Besançon, France).

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Authors and Affiliations

  1. Neurosciences Intégratives et Cliniques EA 481, Laboratoire de Chimie Organique et Thérapeutique, UFR SMP, Université de Franche-Comté, Université Bourgogne Franche-Comté, 19 Rue Ambroise Paré, 25000, Besançon, France

    Isabelle Tomassoli, Mohamed Benchekroun, Oscar M. Bautista-Aguilera, Vincent Luzet, Bernard Refouvelet & Lhassane Ismaili

  2. NanoMedicine, Imagery and Therapeutics Lab EA 4662, UFR Sciences and Techniques, Université de Franche-Comté, Université Bourgogne Franche-Comté, 16, Route de Gray, 25030, Besançon, France

    Guillaume Herlem, Fabien Picaud & Tijani Gharbi

  3. Laboratorio de RMN, Centro de Química Orgánica «Lora-Tamayo» , CSIC, C/Juan de la Cierva, 3, 28006, Madrid, Spain

    María-Luisa Jimeno

  4. Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15213-2582, USA

    Isabelle Tomassoli

  5. Centre de recherche de Gif-sur-Yvette, Institut de Chimie des Substances Naturelles, UPR 2301, CNRS, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France

    Mohamed Benchekroun

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  1. Isabelle Tomassoli
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  2. Guillaume Herlem
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  3. Fabien Picaud
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  4. Mohamed Benchekroun
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  6. Vincent Luzet
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  7. María-Luisa Jimeno
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  8. Tijani Gharbi
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  9. Bernard Refouvelet
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  10. Lhassane Ismaili
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Correspondence to Lhassane Ismaili.

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Tomassoli, I., Herlem, G., Picaud, F. et al. Synthesis, regioselectivity, and DFT analysis of new antioxidant pyrazolo[4,3-c]quinoline-3,4-diones. Monatsh Chem 147, 1069–1079 (2016). https://doi.org/10.1007/s00706-016-1660-7

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  • DOI: https://doi.org/10.1007/s00706-016-1660-7

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