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Understanding the Solid-State Assembly of Pharmaceutically-Relevant N,N-Dimethyl-O-Thiocarbamates in the Absence of Labile Hydrogen Bonds

submitted on 13.09.2020, 09:08 and posted on 14.09.2020, 10:53 by Davin Tan, Zi xuan Ng, Rakesh Ganguly, yongxin Li, Han Sen Soo, Felipe Garcia
There are many pharmaceutical compounds that do not contain N-H, O-H, and S-H hydrogen-bond donor functional groups. Some of these compounds are N,N-disubstituted O-thiocarbamates which exhibit desirable medicinal properties, yet the study of these important molecules in the solid-state has been relatively unexplored. Herein, we report the synthesis and analysis 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 and discern certain packing patterns. 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 associate in the solid-state, with some members of the series displaying isostructural relationships. The crystal structure of a well-known yet unreported O-thiocarbamate drug, Tolnaftate, is also reported. Additionally, Hirshfeld surface analysis was also performed on these compounds as well as several related O-thiocarbamates in the literature.


A*STAR AME IRG (A1783c0003)

NTU start-up grant (M4080552)

MOE Tier 1 grant RG 111/18

MOE Tier 1 grant RT 05/19.

AME IRG grant A1783c0003

AME IRG grant A1783c0002

AME IRG grant A1783c0007


Email Address of Submitting Author


Nanyang Technological University



ORCID For Submitting Author


Declaration of Conflict of Interest

The authors declare no conflict of interest