1-Methyl-5-nitroimidazolium chloride

A combination of hydrogen-bonding and anion-π interactions help form the extended structure of the title salt.


Structure description
The study of nitroimidazole-based compounds remains of interest due to their appearance on the World Health Organization's list of essential drugs (Purgato & Barbui, 2012). Among the numerous functionalized derivatives of imidazoles, 5-nitroimidazoles have long been known to be effective antibiotics (Leiros et al., 2004). Recently, however, 5-nitroimidazole-based compounds have received renewed attention for the potential treatment of a slew of infectious diseases such as leishmaniasis and tuberculosis (Ang et al., 2017). A previous report by Bowden & Izadi (1998) analyzed the antibacterial activities of various derivatives of metronidazole, a compound bearing a 5-nitroimidazole core. In their work, several derivatives of metronidazole were chemically modified and studied with the intent of overcoming some of the disadvantages of 5-nitroimidazolebased pharmaceuticals (Bowden & Izadi, 1998). Furthermore, Miyamoto and coworkers reported the synthesis of a new class of nitroimidazole derivatives to combat drugresistant strains of infections (Miyamoto et al., 2013). Hence, with the renewed interest in data reports these compounds, fundamental structural analysis of nitroimidazoles is of importance to the advancement of drug development.
Herein we report the crystal structure of 1-methyl-5-nitroimidazolium chloride (Fig. 1). While the overall crystalline forces are dominated by the Coulombic interactions between ion pairs, non-covalent interactions will still play a role in the formation of the crystal (Gavezzotti, 2010). The amine hydrogen atom, H3, exhibits the shortest hydrogen bond with the chloride anion with a distance of 2.160 (19) Å (Table 1). The 2-position of imidazolium cations is known to be relatively acidic (Noack et al., 2010). As such, the central aromatic hydrogen (H2) tends to form shorter interactions with anions when compared with the other aromatic H atoms on the heterocyclic cores (Dupont, 2004). This trend is observed within this structure as well with H2 displaying a shorter interaction with the anion (2.62 Å ) than the other aromatic hydrogen H4 (2.78 Å ). As has been observed in related systems, the halide anions surround the cation in distinctive locations facilitating interactions with nearly all atoms of the heterocyclic core (Hunt et al., 2006;Sanchora et al., 2019;Matthews et al., 2015). For example, the chloride anion interacts with the methyl H atoms (H6A, H6B, and H6C) at distances of 3.14, 2.85, and 2.84 Å , respectively.
Nitro moieties are capable of exhibiting a diverse set of non-covalent interactions (Bauzá et al., 2019;Sikorski & Trzybiń ski, 2013). Within the title structure, both nitro O atoms (O1 and O2) participate in interactions with methyl H atoms H6A and H6B at distances of 2.56 and 2.90 Å , respectively. No short interactions with the aromatic H atoms are observed with the nitro group. The nitro moiety is nearly coplanar to the imidazole ring, with an N4-C5-C4-N3 torsion angle of 6.71 (10) o . As demonstrated by Bauzá et al.,holes are present in nitroaromatics, forming an important set of potential interactions (Bauzá et al., 2015). For the title compound, the chloride anion is interacting with both faces of the -hole of the nitro moiety at distances of 3.33 (10) and 3.37 (10) Å . The packing is shown in Fig. 2.

Synthesis and crystallization
The title compound is a hydrolysis product from the synthetic procedure described below, analogous to our previously reported synthesis of 2,3-dimethyl-1H-imidazol-3-ium chloride (Anderson et al., 2020).
In brief, 5-nitroimidazole and trityl chloride were dissolved in separate 50 ml beakers with toluene. The reactants were then combined in a single-necked 100 ml round-bottom flask equipped with a magnetic stir bar and left to stir for 2 days at room temperature. The solvent was removed under vacuum leaving a white solid residue. This solid was washed twice with tetrahydrofuran and recovered via vacuum filtration. Crystals were grown at room temperature by vapor diffusion with acetonitrile as the solvent and tetrahydrofuran as the antisolvent. Colorless crystals of the hydrolyzed byproduct reported herein were observed within one week.

Refinement
For full experimental details including crystal data, data collection and structure refinement details, refer to Table 2.

Figure 1
Constituents of the title salt showing the atom-labeling scheme and 50% probability ellipsoids.

Figure 2
Packing diagram of the title salt.   Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

data-2
IUCrData (2022). 7, x220878 Refinement. Refined as a two-component twin. H atoms attached to carbon atoms were positioned geometrically and constrained to ride on their parent atoms. C-H bond distances were constrained to 0.95 Å for aromatic C-H moieties with U iso (H) = 1.2 × U eq (C), and to 0.98 Å for CH 3 moieties with U iso (H) = 1.5 × U eq (C). The N-H proton on N3 was located as residual electron density and allowed to refine freely.