Journal Article

Structural Characterization of 4-(4-Nitrophenyl)thiomorpholine, a Precursor in Medicinal Chemistry

Goddard, Richard, Imming, Peter, Seidel, Rüdiger W., Palme, Paul R.

2024

Overview

4-(4-nitrophenyl)thiomorpholine, the title compound, has been used as a precursor for the corresponding 4-thiomorpholinoaniline, which is a useful building block in medicinal chemistry. The crystal and molecular structures of the title compound, however, have not been described thus far. We synthesized the title compound by means of a nucleophilic aromatic substitution reaction of 4-fluoronitrobenzene and thiomorpholine and structurally characterized it by X-ray crystallography, DFT calculations, and Hirshfeld surface analysis. In the crystal, the molecule exhibits an approximately CS-symmetric structure, with the nitrogen-bound 4-nitrophenyl group in a quasi axial position on the six-membered thiomorpholine ring in a low-energy chair conformation. The solid-state structure of the title compound is markedly different from that of its morpholine analogue. This can be ascribed to the formation of centrosymmetric dimers through intermolecular C–H···O weak hydrogen bonds involving the methylene groups adjacent to the sulfur atom and face-to-face aromatic stacking.

• Publisher: MDPI AG
• Subject: Bonding strength / Crystal structure / Crystallography / Density functionals / DFT calculation / Heterocyclic compounds / Hirshfeld surface analysis / hydrogen bonding / Hydrogen bonds / Identification and classification / Molecular structure / Nitro compounds / nucleophilic aromatic substitution / Pharmaceutical sciences / Precursors / Software / Solvents / Structural analysis / Structure / Substitution reactions / Surface analysis (chemical) / Symmetry / thiomorpholine / X-ray crystallography