Direct aminolysis of methyl esters with ammonia in continuous flow through Bayesian optimization
- Author
- Bavo Vandekerckhove (UGent) , Stefan Desimpel (UGent) , Bart Ruttens, Massimo Bocus (UGent) , Wim Temmerman (UGent) , Bert Metten, Veronique Van Speybroeck (UGent) , Thomas Heugebaert (UGent) and Christian Stevens (UGent)
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- Abstract
- Amides play a crucial role in the pharmaceutical, animal health and agrochemical industry. Despite the availability of various catalytic systems and coupling reagents, many methods suffered from long reaction times and poor atom economy. The direct synthesis of primary amides remained particularly challenging due to the limited availability of suitable nitrogen sources. In this study, continuous flow technology was explored as a process-intensification approach for the direct amidation of methyl esters to produce primary amides. Methanolic ammonia was employed as a nitrogen source to enhance process efficiency while circumventing the limitations of aqueous ammonia and the hazards of gaseous ammonia. Seventeen substrates were screened to assess their aminolysis reactivity under these conditions. As a proof of concept, methyl picolinate was selected for continuous flow optimization using Bayesian optimization. Therefore, a custom-designed high-pressure, high-temperature continuous flow reactor was utilized to achieve efficient, safe and scalable synthesis (200 degrees C, 50 bar).
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- CHEMISTRY
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Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01JW5VY6HEZ50XFKMQ8VMV70CR
- MLA
- Vandekerckhove, Bavo, et al. “Direct Aminolysis of Methyl Esters with Ammonia in Continuous Flow through Bayesian Optimization.” REACTION CHEMISTRY & ENGINEERING, 2025, doi:10.1039/d5re00163c.
- APA
- Vandekerckhove, B., Desimpel, S., Ruttens, B., Bocus, M., Temmerman, W., Metten, B., … Stevens, C. (2025). Direct aminolysis of methyl esters with ammonia in continuous flow through Bayesian optimization. REACTION CHEMISTRY & ENGINEERING. https://doi.org/10.1039/d5re00163c
- Chicago author-date
- Vandekerckhove, Bavo, Stefan Desimpel, Bart Ruttens, Massimo Bocus, Wim Temmerman, Bert Metten, Veronique Van Speybroeck, Thomas Heugebaert, and Christian Stevens. 2025. “Direct Aminolysis of Methyl Esters with Ammonia in Continuous Flow through Bayesian Optimization.” REACTION CHEMISTRY & ENGINEERING. https://doi.org/10.1039/d5re00163c.
- Chicago author-date (all authors)
- Vandekerckhove, Bavo, Stefan Desimpel, Bart Ruttens, Massimo Bocus, Wim Temmerman, Bert Metten, Veronique Van Speybroeck, Thomas Heugebaert, and Christian Stevens. 2025. “Direct Aminolysis of Methyl Esters with Ammonia in Continuous Flow through Bayesian Optimization.” REACTION CHEMISTRY & ENGINEERING. doi:10.1039/d5re00163c.
- Vancouver
- 1.Vandekerckhove B, Desimpel S, Ruttens B, Bocus M, Temmerman W, Metten B, et al. Direct aminolysis of methyl esters with ammonia in continuous flow through Bayesian optimization. REACTION CHEMISTRY & ENGINEERING. 2025;
- IEEE
- [1]B. Vandekerckhove et al., “Direct aminolysis of methyl esters with ammonia in continuous flow through Bayesian optimization,” REACTION CHEMISTRY & ENGINEERING, 2025.
@article{01JW5VY6HEZ50XFKMQ8VMV70CR,
abstract = {{Amides play a crucial role in the pharmaceutical, animal health and agrochemical industry. Despite the availability of various catalytic systems and coupling reagents, many methods suffered from long reaction times and poor atom economy. The direct synthesis of primary amides remained particularly challenging due to the limited availability of suitable nitrogen sources. In this study, continuous flow technology was explored as a process-intensification approach for the direct amidation of methyl esters to produce primary amides. Methanolic ammonia was employed as a nitrogen source to enhance process efficiency while circumventing the limitations of aqueous ammonia and the hazards of gaseous ammonia. Seventeen substrates were screened to assess their aminolysis reactivity under these conditions. As a proof of concept, methyl picolinate was selected for continuous flow optimization using Bayesian optimization. Therefore, a custom-designed high-pressure, high-temperature continuous flow reactor was utilized to achieve efficient, safe and scalable synthesis (200 degrees C, 50 bar).}},
author = {{Vandekerckhove, Bavo and Desimpel, Stefan and Ruttens, Bart and Bocus, Massimo and Temmerman, Wim and Metten, Bert and Van Speybroeck, Veronique and Heugebaert, Thomas and Stevens, Christian}},
issn = {{2058-9883}},
journal = {{REACTION CHEMISTRY & ENGINEERING}},
keywords = {{CHEMISTRY}},
language = {{eng}},
pages = {{10}},
title = {{Direct aminolysis of methyl esters with ammonia in continuous flow through Bayesian optimization}},
url = {{http://doi.org/10.1039/d5re00163c}},
year = {{2025}},
}
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