LAPSE:2023.36924
Published Article
LAPSE:2023.36924
Microwave-Assisted Reductive Amination under Heterogeneous Catalysis for the Synthesis of β-Adrenergic Agonist and Related Structures
November 30, 2023
Reductive amination is a powerful tool in sustainable organic synthesis that allows chemists to access a wide range of valuable amine products using renewable feedstocks and mild reaction conditions, with minimal waste generation. Practical applications can be found in various fields, including pharmaceuticals, contributing to greener and more sustainable chemical processes. In this work, we present a heterogeneous (Rh and Pt) catalyzed protocol for the fast and efficient synthesis of ractopamine hydrochloride (β-adrenergic drug) under microwave-assisted reductive amination protocol starting from raspberry ketone and octopamine. Microwave (MW) successfully accelerated the hydrogenation reaction and reduced the reaction time from 13 h to only 3 h under mild conditions (50 °C at 10 bar). The best catalysts were Pt/C and Rh/C, which led to high conversion and selectivity towards ractopamine:HCl. Different solvents and ketone substrates were also experimented. Acetophenone, cyclohexanone, and 2-butanone reacted at lower H2 pressure (5 bar), and highest selectivity was observed with cyclohexanone (99%). These preliminary experiments may be useful for further process improvements in the synthesis of β-adrenergic agonists and related structures and underline the positive synergy between MW and heterogeneous catalysis.
Keywords
microwave-assisted reactions, Process Intensification, ractopamine:HCl, raspberry ketone, reductive amination, transition-metal catalysts
Suggested Citation
Bucciol F, Colia M, Canova E, Grillo G, Calcio Gaudino E, Cravotto G. Microwave-Assisted Reductive Amination under Heterogeneous Catalysis for the Synthesis of β-Adrenergic Agonist and Related Structures. (2023). LAPSE:2023.36924
Author Affiliations
Bucciol F: Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, 10125 Turin, Italy [ORCID]
Colia M: Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, 10125 Turin, Italy; Huvepharma Italy Srl, Via Roberto Lepetit, 142, 12075 Garessio, Italy
Canova E: Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, 10125 Turin, Italy; Huvepharma Italy Srl, Via Roberto Lepetit, 142, 12075 Garessio, Italy
Grillo G: Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, 10125 Turin, Italy [ORCID]
Calcio Gaudino E: Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, 10125 Turin, Italy [ORCID]
Cravotto G: Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, 10125 Turin, Italy [ORCID]
Journal Name
Processes
Volume
11
Issue
9
First Page
2602
Year
2023
Publication Date
2023-08-31
Published Version
ISSN
2227-9717
Version Comments
Original Submission
Other Meta
PII: pr11092602, Publication Type: Journal Article
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LAPSE:2023.36924
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doi:10.3390/pr11092602
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Nov 30, 2023
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Nov 30, 2023
 
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Nov 30, 2023
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Original Submitter
Calvin Tsay
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