A Ligand-Free Approach towards Coumarin Analogs via Natural Deep Eutectic Solvent-Mediated Suzuki–Miyaura Coupling
A ligand-free approach for the Suzuki-Miyaura cross coupling reaction using Natural Deep Eutectic Solvents (NaDES) towards coumarin analogs is described. A model reaction between the synthetically prepared 3-(4-acetyloxy-phenyl)-6-bromo-4-methyl-coumarin (<b>3b</b>) and phenylboronic aci...
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2024-09-01
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| author | Annita Katopodi Nikolaos Nikolaou Vasiliki Kakokefalou Eleni Alexandratou Manolis Matzapetakis Maria Zervou Anastasia Detsi |
| author_facet | Annita Katopodi Nikolaos Nikolaou Vasiliki Kakokefalou Eleni Alexandratou Manolis Matzapetakis Maria Zervou Anastasia Detsi |
| author_sort | Annita Katopodi |
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| description | A ligand-free approach for the Suzuki-Miyaura cross coupling reaction using Natural Deep Eutectic Solvents (NaDES) towards coumarin analogs is described. A model reaction between the synthetically prepared 3-(4-acetyloxy-phenyl)-6-bromo-4-methyl-coumarin (<b>3b</b>) and phenylboronic acid was performed in five different NaDES as well as in pure glycerol, using two inorganic bases and palladium catalysts. The reaction proceeded smoothly in Choline Chloride/Glycerol (ChCl/Gly) and Betaine/Glycerol (Bet/Gly) NaDES at 90 °C in 24 h, affording the desired product in high yields up to 95%. The combination of K<sub>2</sub>CO<sub>3</sub>, Pd(OAc)<sub>2</sub> and ChCl/Gly NaDES provided optimum yields and high purity of the desired compounds, while the solvent was successfully recycled and reused up to two times. The developed methodology is applicable to boronic acids bearing various substituents. The formation of palladium nanoparticles in the reaction mixture was observed, and the size of the nanoparticles was associated with the reaction yield. In addition, in all the glycerol-based NaDES, an effective removal of the acetyl group of the acetyloxy–coumarin analogs was observed; thus, it is noteworthy that the Suzuki–Miyaura coupling and the deacetylation reaction were achieved in one pot. The ten novel coumarin derivatives synthesized were structurally characterized using 1D and 2D NMR spectroscopy and were tested for their cytotoxicity against the A431 squamous cancer cell line, presenting significant activity. |
| format | Article |
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| publishDate | 2024-09-01 |
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| spelling | doaj-art-7e8a6c9cc264436db50bfe195ae355c32025-08-20T01:55:42ZengMDPI AGMolecules1420-30492024-09-012918439810.3390/molecules29184398A Ligand-Free Approach towards Coumarin Analogs via Natural Deep Eutectic Solvent-Mediated Suzuki–Miyaura CouplingAnnita Katopodi0Nikolaos Nikolaou1Vasiliki Kakokefalou2Eleni Alexandratou3Manolis Matzapetakis4Maria Zervou5Anastasia Detsi6Laboratory of Organic Chemistry, School of Chemical Engineering, National Technical University of Athens, Zografou Campus, 15780 Athens, GreeceLaboratory of Organic Chemistry, School of Chemical Engineering, National Technical University of Athens, Zografou Campus, 15780 Athens, GreeceLaboratory of Organic Chemistry, School of Chemical Engineering, National Technical University of Athens, Zografou Campus, 15780 Athens, GreeceLaboratory of Biomedical Optics and Applied Biophysics, School of Electrical and Computer Engineering, National Technical University of Athens, Zografou Campus, 15780 Athens, GreeceInstitute of Chemical Biology, National Hellenic Research Foundation, 48 Vas. Constantinou Ave., 11635 Athens, GreeceInstitute of Chemical Biology, National Hellenic Research Foundation, 48 Vas. Constantinou Ave., 11635 Athens, GreeceLaboratory of Organic Chemistry, School of Chemical Engineering, National Technical University of Athens, Zografou Campus, 15780 Athens, GreeceA ligand-free approach for the Suzuki-Miyaura cross coupling reaction using Natural Deep Eutectic Solvents (NaDES) towards coumarin analogs is described. A model reaction between the synthetically prepared 3-(4-acetyloxy-phenyl)-6-bromo-4-methyl-coumarin (<b>3b</b>) and phenylboronic acid was performed in five different NaDES as well as in pure glycerol, using two inorganic bases and palladium catalysts. The reaction proceeded smoothly in Choline Chloride/Glycerol (ChCl/Gly) and Betaine/Glycerol (Bet/Gly) NaDES at 90 °C in 24 h, affording the desired product in high yields up to 95%. The combination of K<sub>2</sub>CO<sub>3</sub>, Pd(OAc)<sub>2</sub> and ChCl/Gly NaDES provided optimum yields and high purity of the desired compounds, while the solvent was successfully recycled and reused up to two times. The developed methodology is applicable to boronic acids bearing various substituents. The formation of palladium nanoparticles in the reaction mixture was observed, and the size of the nanoparticles was associated with the reaction yield. In addition, in all the glycerol-based NaDES, an effective removal of the acetyl group of the acetyloxy–coumarin analogs was observed; thus, it is noteworthy that the Suzuki–Miyaura coupling and the deacetylation reaction were achieved in one pot. The ten novel coumarin derivatives synthesized were structurally characterized using 1D and 2D NMR spectroscopy and were tested for their cytotoxicity against the A431 squamous cancer cell line, presenting significant activity.https://www.mdpi.com/1420-3049/29/18/4398Suzuki–Miyaura reactionDeep Eutectic Solventscoumarinspalladium nanoparticles |
| spellingShingle | Annita Katopodi Nikolaos Nikolaou Vasiliki Kakokefalou Eleni Alexandratou Manolis Matzapetakis Maria Zervou Anastasia Detsi A Ligand-Free Approach towards Coumarin Analogs via Natural Deep Eutectic Solvent-Mediated Suzuki–Miyaura Coupling Molecules Suzuki–Miyaura reaction Deep Eutectic Solvents coumarins palladium nanoparticles |
| title | A Ligand-Free Approach towards Coumarin Analogs via Natural Deep Eutectic Solvent-Mediated Suzuki–Miyaura Coupling |
| title_full | A Ligand-Free Approach towards Coumarin Analogs via Natural Deep Eutectic Solvent-Mediated Suzuki–Miyaura Coupling |
| title_fullStr | A Ligand-Free Approach towards Coumarin Analogs via Natural Deep Eutectic Solvent-Mediated Suzuki–Miyaura Coupling |
| title_full_unstemmed | A Ligand-Free Approach towards Coumarin Analogs via Natural Deep Eutectic Solvent-Mediated Suzuki–Miyaura Coupling |
| title_short | A Ligand-Free Approach towards Coumarin Analogs via Natural Deep Eutectic Solvent-Mediated Suzuki–Miyaura Coupling |
| title_sort | ligand free approach towards coumarin analogs via natural deep eutectic solvent mediated suzuki miyaura coupling |
| topic | Suzuki–Miyaura reaction Deep Eutectic Solvents coumarins palladium nanoparticles |
| url | https://www.mdpi.com/1420-3049/29/18/4398 |
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