Continuous Flow Photochemical Synthesis of 3-Methyl-4-arylmethylene Isoxazole-5(4H)-ones through Organic Photoredox Catalysis and Investigation of Their Larvicidal Activity
Isoxazole-5(4H)-ones are heteropentacycle compounds found in several bioactive molecules with pharmaceutical and agrochemical properties. A well-known multicomponent reaction between β-ketoester, hydroxylamine, and aromatic aldehydes leads to 3-methyl-4-arylmethylene isoxazole-5(4H)-ones, in mild co...
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MDPI AG
2023-03-01
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| Series: | Catalysts |
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| Online Access: | https://www.mdpi.com/2073-4344/13/3/518 |
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| author | Ana Beatriz S. Sampaio Mônica Shigemi S. Mori Lorena C. Albernaz Laila S. Espindola Carlos Eduardo M. Salvador Carlos Kleber Z. Andrade |
| author_facet | Ana Beatriz S. Sampaio Mônica Shigemi S. Mori Lorena C. Albernaz Laila S. Espindola Carlos Eduardo M. Salvador Carlos Kleber Z. Andrade |
| author_sort | Ana Beatriz S. Sampaio |
| collection | DOAJ |
| description | Isoxazole-5(4H)-ones are heteropentacycle compounds found in several bioactive molecules with pharmaceutical and agrochemical properties. A well-known multicomponent reaction between β-ketoester, hydroxylamine, and aromatic aldehydes leads to 3-methyl-4-arylmethylene isoxazole-5(4H)-ones, in mild conditions. The initial purpose of this work was to investigate whether the reaction might be induced by light, as described in previous works. Remarkable results were obtained using a high-power lamp, reducing reaction times compared to methodologies that used heating or catalysis. Since there are many examples of successful continuous flow heterocycle synthesis, including photochemical reactions, the study evolved to run the reaction in flow conditions and scale up the synthesis of isoxazolones using a photochemical reactor set-up. Eight different compounds were obtained, and among them, three showed larvicidal activity on immature forms of <i>Aedes aegypti</i> in tests that investigated its growth inhibitory character. Mechanistic investigations indicate that the reactions occur through organic photoredox catalysis. |
| first_indexed | 2024-03-11T06:47:55Z |
| format | Article |
| id | doaj.art-b47b605e823c47fe82c1cc43a2e489db |
| institution | Directory Open Access Journal |
| issn | 2073-4344 |
| language | English |
| last_indexed | 2024-03-11T06:47:55Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Catalysts |
| spelling | doaj.art-b47b605e823c47fe82c1cc43a2e489db2023-11-17T10:10:33ZengMDPI AGCatalysts2073-43442023-03-0113351810.3390/catal13030518Continuous Flow Photochemical Synthesis of 3-Methyl-4-arylmethylene Isoxazole-5(4H)-ones through Organic Photoredox Catalysis and Investigation of Their Larvicidal ActivityAna Beatriz S. Sampaio0Mônica Shigemi S. Mori1Lorena C. Albernaz2Laila S. Espindola3Carlos Eduardo M. Salvador4Carlos Kleber Z. Andrade5Laboratório de Química Metodológica e Orgânica Sintética (LaQMOS), Instituto de Química, Universidade de Brasília, Campus Universitário Asa Norte, Brasilia 70904-970, BrazilFaculdade de Ciências da Saúde, Universidade de Brasília, Campus Universitário Asa Norte, Brasilia 70904-970, BrazilFaculdade de Ciências da Saúde, Universidade de Brasília, Campus Universitário Asa Norte, Brasilia 70904-970, BrazilFaculdade de Ciências da Saúde, Universidade de Brasília, Campus Universitário Asa Norte, Brasilia 70904-970, BrazilLaboratório de Química Metodológica e Orgânica Sintética (LaQMOS), Instituto de Química, Universidade de Brasília, Campus Universitário Asa Norte, Brasilia 70904-970, BrazilLaboratório de Química Metodológica e Orgânica Sintética (LaQMOS), Instituto de Química, Universidade de Brasília, Campus Universitário Asa Norte, Brasilia 70904-970, BrazilIsoxazole-5(4H)-ones are heteropentacycle compounds found in several bioactive molecules with pharmaceutical and agrochemical properties. A well-known multicomponent reaction between β-ketoester, hydroxylamine, and aromatic aldehydes leads to 3-methyl-4-arylmethylene isoxazole-5(4H)-ones, in mild conditions. The initial purpose of this work was to investigate whether the reaction might be induced by light, as described in previous works. Remarkable results were obtained using a high-power lamp, reducing reaction times compared to methodologies that used heating or catalysis. Since there are many examples of successful continuous flow heterocycle synthesis, including photochemical reactions, the study evolved to run the reaction in flow conditions and scale up the synthesis of isoxazolones using a photochemical reactor set-up. Eight different compounds were obtained, and among them, three showed larvicidal activity on immature forms of <i>Aedes aegypti</i> in tests that investigated its growth inhibitory character. Mechanistic investigations indicate that the reactions occur through organic photoredox catalysis.https://www.mdpi.com/2073-4344/13/3/518isoxazolonephotochemistrycontinuous flowlarvicidal activity |
| spellingShingle | Ana Beatriz S. Sampaio Mônica Shigemi S. Mori Lorena C. Albernaz Laila S. Espindola Carlos Eduardo M. Salvador Carlos Kleber Z. Andrade Continuous Flow Photochemical Synthesis of 3-Methyl-4-arylmethylene Isoxazole-5(4H)-ones through Organic Photoredox Catalysis and Investigation of Their Larvicidal Activity Catalysts isoxazolone photochemistry continuous flow larvicidal activity |
| title | Continuous Flow Photochemical Synthesis of 3-Methyl-4-arylmethylene Isoxazole-5(4H)-ones through Organic Photoredox Catalysis and Investigation of Their Larvicidal Activity |
| title_full | Continuous Flow Photochemical Synthesis of 3-Methyl-4-arylmethylene Isoxazole-5(4H)-ones through Organic Photoredox Catalysis and Investigation of Their Larvicidal Activity |
| title_fullStr | Continuous Flow Photochemical Synthesis of 3-Methyl-4-arylmethylene Isoxazole-5(4H)-ones through Organic Photoredox Catalysis and Investigation of Their Larvicidal Activity |
| title_full_unstemmed | Continuous Flow Photochemical Synthesis of 3-Methyl-4-arylmethylene Isoxazole-5(4H)-ones through Organic Photoredox Catalysis and Investigation of Their Larvicidal Activity |
| title_short | Continuous Flow Photochemical Synthesis of 3-Methyl-4-arylmethylene Isoxazole-5(4H)-ones through Organic Photoredox Catalysis and Investigation of Their Larvicidal Activity |
| title_sort | continuous flow photochemical synthesis of 3 methyl 4 arylmethylene isoxazole 5 4h ones through organic photoredox catalysis and investigation of their larvicidal activity |
| topic | isoxazolone photochemistry continuous flow larvicidal activity |
| url | https://www.mdpi.com/2073-4344/13/3/518 |
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