Preprint Communication Version 1 Preserved in Portico This version is not peer-reviewed

Improved Synthesis of β-Adrenergic Agonist and Related Structures by Microwave-Assisted Metal-Catalysed Reductive Amination

Fabio Bucciol
ORCID logo ,
Mariachiara Colia
,
Erica Canova
,
Giorgio Grillo
ORCID logo ,
Emanuela Calcio Gaudino
* ORCID logo ,
Giancarlo Cravotto
*
Version 1 : Received: 4 August 2023 / Approved: 7 August 2023 / Online: 7 August 2023 (12:20:08 CEST)

A peer-reviewed article of this Preprint also exists.

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. Processes 2023, 11, 2602. 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. Processes 2023, 11, 2602.

Abstract

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, mild reaction con-ditions, and 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) catalysed protocol for the fast and efficient synthesis of ractopamine hydrochloride (-adrenergic drug) under MW-assisted reductive ami-nation protocol starting from raspberry ketone and octapamine. Microwave (MW) successfully accelerated the hydrogenation reaction and reduced the reaction time from 13 hours to only 3 hours 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. The solvent has a significant effect on the reaction outcome. The replacement of methanol with other solvents had a negative impact on the reaction yield. We also replaced the raspberry ketone with other ketone substrates, especially cyclohexanone. These preliminary experiments may be useful for further process improvements in the synthesis of β-adrenergic agonists and related structures.

Keywords

reductive amination; process intensification; microwave-assisted reactions; transition-metal catalysts; ractopamine:HCl; raspberry ketone

Subject

Chemistry and Materials Science, Medicinal Chemistry

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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