Issue 3, 2024

The role of the milling environment on the copper-catalysed mechanochemical synthesis of tolbutamide

Abstract

We provide a systematic investigation of the role of atmospheric oxygen and choice of milling assembly (i.e., the milling jar and ball materials) on a prototypical medicinal mechanochemistry reaction: the copper-catalysed coupling of isocyanate and sulfonamide to form the sulfonylurea tolbutamide. Using in-house developed equipment for work under controlled-atmosphere milling conditions, we reveal that the reaction is in fact catalysed by Cu(II) species, with the conventionally used CuCl acting as a pre-catalyst, which becomes activated via aerobic oxidation during milling. Unexpectedly, the choice of milling jar material was found to have a profound effect on the coupling, with aluminium jars effectively “shutting down” reactivity, most likely by preventing CuCl oxidation. Hence, opposite to direct mechanocatalysis, a term used to describe reactions promoted by the milling jar or ball material, this observation reveals the possibility of direct mechanoinhibition – i.e., the inhibition of a mechanochemical reaction by the jar. These results highlight the importance of systematic investigations of both the milling assembly, as well as atmosphere, in understanding and controlling organic mechanochemical transformations.

Graphical abstract: The role of the milling environment on the copper-catalysed mechanochemical synthesis of tolbutamide

Supplementary files

Article information

Article type
Paper
Submitted
02 Apr 2024
Accepted
06 May 2024
First published
06 May 2024
This article is Open Access
Creative Commons BY-NC license

RSC Mechanochem., 2024,1, 289-295

The role of the milling environment on the copper-catalysed mechanochemical synthesis of tolbutamide

K. Floyd, L. Gonnet, T. Friščić and J. Batteas, RSC Mechanochem., 2024, 1, 289 DOI: 10.1039/D4MR00031E

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements