Scalable and sustainable reductive amidation of nitroarenes, nitroalkenes, and nitroalkyls with acyl saccharins in aqueous media
Abstract Amide bond formation is essential in both organic and medicinal chemistry, however, most existing methods present poor ecological efficiency. Here, we report a scalable and sustainable method for synthesizing N-substituted amides from nitroarenes, nitroalkenes, nitroalkyls, and acyl sacchar...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-025-01464-8 |
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| author | Sunil L. Khamkar Rayala Mohan J. Santhosh Harish M. Shinde Kishor L. Handore S. Venkata Mohan D. Srinivasa Reddy |
| author_facet | Sunil L. Khamkar Rayala Mohan J. Santhosh Harish M. Shinde Kishor L. Handore S. Venkata Mohan D. Srinivasa Reddy |
| author_sort | Sunil L. Khamkar |
| collection | DOAJ |
| description | Abstract Amide bond formation is essential in both organic and medicinal chemistry, however, most existing methods present poor ecological efficiency. Here, we report a scalable and sustainable method for synthesizing N-substituted amides from nitroarenes, nitroalkenes, nitroalkyls, and acyl saccharin in aqueous media. This atom-efficient approach avoids column chromatography, offers high yield, and is compatible with various functional groups. It is applicable to synthesize Dispyrin, a bromopyrrole alkaloid, amide-based drugs, and agrochemicals, including paracetamol, with solvent and saccharin recycling. A comprehensive Life Cycle Assessment (LCA; ISO 14044) was conducted to evaluate the environmental impacts and sustainability of nine Active Pharmaceutical Ingredients (APIs) produced via Amidation Route (AR) and Saccharin Amidation Route (SAR). The study shows SAR methods reduce carbon footprints and environmental impacts compared to AR methods, being carbon-negative and resource-efficient. Additional reductions can be achieved through saccharin recycling and the integration of renewable energy sources, demonstrating saccharin-based processes potential to minimize environmental burdens in pharmaceutical synthesis. |
| format | Article |
| id | doaj-art-6201bedc188f41a9b9213fc00722a85a |
| institution | Kabale University |
| issn | 2399-3669 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj-art-6201bedc188f41a9b9213fc00722a85a2025-08-20T03:45:11ZengNature PortfolioCommunications Chemistry2399-36692025-06-018111510.1038/s42004-025-01464-8Scalable and sustainable reductive amidation of nitroarenes, nitroalkenes, and nitroalkyls with acyl saccharins in aqueous mediaSunil L. Khamkar0Rayala Mohan1J. Santhosh2Harish M. Shinde3Kishor L. Handore4S. Venkata Mohan5D. Srinivasa Reddy6Academy of Scientific and Innovative Research (AcSIR)Bioengineering and Environmental Sciences Lab, Department of Energy and Environmental Engineering (DEEE), CSIR-Indian Institute of Chemical Technology (CSIR-IICT)Academy of Scientific and Innovative Research (AcSIR)BASF Innovation Campus Mumbai, BASF Chemicals India Pvt. Ltd.Academy of Scientific and Innovative Research (AcSIR)Academy of Scientific and Innovative Research (AcSIR)Academy of Scientific and Innovative Research (AcSIR)Abstract Amide bond formation is essential in both organic and medicinal chemistry, however, most existing methods present poor ecological efficiency. Here, we report a scalable and sustainable method for synthesizing N-substituted amides from nitroarenes, nitroalkenes, nitroalkyls, and acyl saccharin in aqueous media. This atom-efficient approach avoids column chromatography, offers high yield, and is compatible with various functional groups. It is applicable to synthesize Dispyrin, a bromopyrrole alkaloid, amide-based drugs, and agrochemicals, including paracetamol, with solvent and saccharin recycling. A comprehensive Life Cycle Assessment (LCA; ISO 14044) was conducted to evaluate the environmental impacts and sustainability of nine Active Pharmaceutical Ingredients (APIs) produced via Amidation Route (AR) and Saccharin Amidation Route (SAR). The study shows SAR methods reduce carbon footprints and environmental impacts compared to AR methods, being carbon-negative and resource-efficient. Additional reductions can be achieved through saccharin recycling and the integration of renewable energy sources, demonstrating saccharin-based processes potential to minimize environmental burdens in pharmaceutical synthesis.https://doi.org/10.1038/s42004-025-01464-8 |
| spellingShingle | Sunil L. Khamkar Rayala Mohan J. Santhosh Harish M. Shinde Kishor L. Handore S. Venkata Mohan D. Srinivasa Reddy Scalable and sustainable reductive amidation of nitroarenes, nitroalkenes, and nitroalkyls with acyl saccharins in aqueous media Communications Chemistry |
| title | Scalable and sustainable reductive amidation of nitroarenes, nitroalkenes, and nitroalkyls with acyl saccharins in aqueous media |
| title_full | Scalable and sustainable reductive amidation of nitroarenes, nitroalkenes, and nitroalkyls with acyl saccharins in aqueous media |
| title_fullStr | Scalable and sustainable reductive amidation of nitroarenes, nitroalkenes, and nitroalkyls with acyl saccharins in aqueous media |
| title_full_unstemmed | Scalable and sustainable reductive amidation of nitroarenes, nitroalkenes, and nitroalkyls with acyl saccharins in aqueous media |
| title_short | Scalable and sustainable reductive amidation of nitroarenes, nitroalkenes, and nitroalkyls with acyl saccharins in aqueous media |
| title_sort | scalable and sustainable reductive amidation of nitroarenes nitroalkenes and nitroalkyls with acyl saccharins in aqueous media |
| url | https://doi.org/10.1038/s42004-025-01464-8 |
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