Issue 48, 2020

Investigating the solid-state assembly of pharmaceutically-relevant N,N-dimethyl-O-thiocarbamates in the absence of labile hydrogen bonds

Abstract

There are many active pharmaceutical ingredients that lack N–H, O–H and S–H hydrogen-bond donor functional groups. N,N-Disubstituted O-thiocarbamates are examples of molecules that display such a feature. Despite the desirable medicinal properties displayed by some N,N-disubstituted O-thiocarbamates, the study of the solid-state properties of these compounds has been relatively unexplored. Herein, we report the synthesis and analysis of the structures and properties of a series of N,N-dimethyl-O-thiocarbamates, and use X-ray diffraction techniques to gain insight into how these molecules self-assemble in the solid-state. As part of our work, we report for the first time the crystal structure of tolnaftate, an active pharmaceutical ingredient that is indicated for the treatment of fungal infections. It was observed that the aryl-thiocarbamate C–O bonds are twisted such that the planar aryl and carbamate moieties are orthogonal. Such a non-planar molecular geometry affects the way the molecules pack and crystal structure analyses revealed four general modes in which the molecules can assemble in the solid-state, with some members of the series displaying isostructural relationships. Computational modelling of the cohesive energy densities in the crystals suggests that there is no single stacking type that is associated with greater stability. However, crystals with a combination of high packing index and π⋯π stacking interactions appear to display large cohesive energy densities. The lack of strong hydrogen bonding interactions in the crystals also leads to relatively low Young's moduli that are within a narrow range of 10–15 GPa for all 14 crystal structures reported.

Graphical abstract: Investigating the solid-state assembly of pharmaceutically-relevant N,N-dimethyl-O-thiocarbamates in the absence of labile hydrogen bonds

Supplementary files

Article information

Article type
Communication
Submitted
13 Sept. 2020
Accepted
29 Okt. 2020
First published
30 Okt. 2020

CrystEngComm, 2020,22, 8290-8298

Investigating the solid-state assembly of pharmaceutically-relevant N,N-dimethyl-O-thiocarbamates in the absence of labile hydrogen bonds

D. Tan, Z. X. Ng, R. Ganguly, Y. Li, H. S. Soo, S. Mohamed and F. García, CrystEngComm, 2020, 22, 8290 DOI: 10.1039/D0CE01336F

To request permission to reproduce material from this article, 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 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