Environmentally Friendly Green <i>O</i>-Alkylation Reaction for Ethenzamide Synthesis
Ethenzamide (2-ethoxybenzamide), besides acetylsalicylic acid, is one of the mostly used salicylic acid derivatives in pharmaceuticals. It has analgesic and anti-inflammatory effects that originate from the inhibition of cyclooxygenase (COX-1) activity, thus blocking prostaglandin synthesis. In this...
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MDPI AG
2025-01-01
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| author | Paulina Niedziejko-Ćwiertnia Anna Karolina Drabczyk Damian Kułaga Patrycja Podobińska Wojciech Bachowski Kamila Zeńczak-Tomera Piotr Michorczyk Ruilong Sheng Jolanta Jaśkowska |
| author_facet | Paulina Niedziejko-Ćwiertnia Anna Karolina Drabczyk Damian Kułaga Patrycja Podobińska Wojciech Bachowski Kamila Zeńczak-Tomera Piotr Michorczyk Ruilong Sheng Jolanta Jaśkowska |
| author_sort | Paulina Niedziejko-Ćwiertnia |
| collection | DOAJ |
| description | Ethenzamide (2-ethoxybenzamide), besides acetylsalicylic acid, is one of the mostly used salicylic acid derivatives in pharmaceuticals. It has analgesic and anti-inflammatory effects that originate from the inhibition of cyclooxygenase (COX-1) activity, thus blocking prostaglandin synthesis. In this work, efficient and eco-friendly methods were developed for the synthesis of ethenzamide via the <i>O</i>-alkylation reaction of salicylamide. The reactions were carried out under conventional conditions in a solvent-free system using variant solvents and different phase transfer catalysts (PTC) in the presence of microwave radiation or ultrasonic conditions. It was shown that in solvent-free conditions using TBAB as a catalyst, ethenzamide can be obtained within 15 min at 80 °C with 79% yield. Meanwhile, using microwave radiation under the same conditions, the reaction time can be shortened to 90 s with 92% yield. Notably, high yields can be achieved under PTC in water (or organic solvent-free) conditions using microwave radiation (2 min, 94%) or ultrasound (10 min, 95% efficiency). The studies prove that the PTC synthesis process of ethenzamide can be conducted under mild conditions, with a shorter reaction time and remarkably lower energy consumption in comparison to conventional processes, thus actualizing “green chemistry” for practical ethenzamide preparation. |
| format | Article |
| id | doaj-art-b70e6a4cde694a2f93bd0891da99f53c |
| institution | DOAJ |
| issn | 2076-3417 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Applied Sciences |
| spelling | doaj-art-b70e6a4cde694a2f93bd0891da99f53c2025-08-20T02:48:09ZengMDPI AGApplied Sciences2076-34172025-01-01153134210.3390/app15031342Environmentally Friendly Green <i>O</i>-Alkylation Reaction for Ethenzamide SynthesisPaulina Niedziejko-Ćwiertnia0Anna Karolina Drabczyk1Damian Kułaga2Patrycja Podobińska3Wojciech Bachowski4Kamila Zeńczak-Tomera5Piotr Michorczyk6Ruilong Sheng7Jolanta Jaśkowska8Faculty of Chemical Engineering and Technology, Cracow University of Technology, 24 Warszawska Street, 31-155 Cracow, PolandFaculty of Chemical Engineering and Technology, Cracow University of Technology, 24 Warszawska Street, 31-155 Cracow, PolandFaculty of Chemical Engineering and Technology, Cracow University of Technology, 24 Warszawska Street, 31-155 Cracow, PolandFaculty of Chemical Engineering and Technology, Cracow University of Technology, 24 Warszawska Street, 31-155 Cracow, PolandFaculty of Chemical Engineering and Technology, Cracow University of Technology, 24 Warszawska Street, 31-155 Cracow, PolandFaculty of Chemical Engineering and Technology, Cracow University of Technology, 24 Warszawska Street, 31-155 Cracow, PolandFaculty of Chemical Engineering and Technology, Cracow University of Technology, 24 Warszawska Street, 31-155 Cracow, PolandCQM—Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9020-105 Funchal, PortugalCQM—Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9020-105 Funchal, PortugalEthenzamide (2-ethoxybenzamide), besides acetylsalicylic acid, is one of the mostly used salicylic acid derivatives in pharmaceuticals. It has analgesic and anti-inflammatory effects that originate from the inhibition of cyclooxygenase (COX-1) activity, thus blocking prostaglandin synthesis. In this work, efficient and eco-friendly methods were developed for the synthesis of ethenzamide via the <i>O</i>-alkylation reaction of salicylamide. The reactions were carried out under conventional conditions in a solvent-free system using variant solvents and different phase transfer catalysts (PTC) in the presence of microwave radiation or ultrasonic conditions. It was shown that in solvent-free conditions using TBAB as a catalyst, ethenzamide can be obtained within 15 min at 80 °C with 79% yield. Meanwhile, using microwave radiation under the same conditions, the reaction time can be shortened to 90 s with 92% yield. Notably, high yields can be achieved under PTC in water (or organic solvent-free) conditions using microwave radiation (2 min, 94%) or ultrasound (10 min, 95% efficiency). The studies prove that the PTC synthesis process of ethenzamide can be conducted under mild conditions, with a shorter reaction time and remarkably lower energy consumption in comparison to conventional processes, thus actualizing “green chemistry” for practical ethenzamide preparation.https://www.mdpi.com/2076-3417/15/3/1342<i>O</i>-alkylationgreen synthesissalicylamideethenzamidephase transfer catalysts (PTC)solvent-free synthesis |
| spellingShingle | Paulina Niedziejko-Ćwiertnia Anna Karolina Drabczyk Damian Kułaga Patrycja Podobińska Wojciech Bachowski Kamila Zeńczak-Tomera Piotr Michorczyk Ruilong Sheng Jolanta Jaśkowska Environmentally Friendly Green <i>O</i>-Alkylation Reaction for Ethenzamide Synthesis Applied Sciences <i>O</i>-alkylation green synthesis salicylamide ethenzamide phase transfer catalysts (PTC) solvent-free synthesis |
| title | Environmentally Friendly Green <i>O</i>-Alkylation Reaction for Ethenzamide Synthesis |
| title_full | Environmentally Friendly Green <i>O</i>-Alkylation Reaction for Ethenzamide Synthesis |
| title_fullStr | Environmentally Friendly Green <i>O</i>-Alkylation Reaction for Ethenzamide Synthesis |
| title_full_unstemmed | Environmentally Friendly Green <i>O</i>-Alkylation Reaction for Ethenzamide Synthesis |
| title_short | Environmentally Friendly Green <i>O</i>-Alkylation Reaction for Ethenzamide Synthesis |
| title_sort | environmentally friendly green i o i alkylation reaction for ethenzamide synthesis |
| topic | <i>O</i>-alkylation green synthesis salicylamide ethenzamide phase transfer catalysts (PTC) solvent-free synthesis |
| url | https://www.mdpi.com/2076-3417/15/3/1342 |
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