aAve Maria University, Department of Chemistry and Physics, 5050 Ave Maria Blvd, Ave Maria, Florida 34142, USA, bDepartment of Chemistry and Physics, Florida Gulf Coast University, 10501 FGCU Blvd. South, Fort Myers, Florida 33965, USA, cPurdue University, Department of Chemistry, 560 Oval Drive, West Lafayette, Indiana 47907, USA, and dDepartment of Chemistry, State University of New York at Oswego, Oswego, New York 13126, USA
*Correspondence e-mail: Patrick.Hillesheim@avemaria.edu
The title salt, C4H6N3O2+·Cl−, exhibits multiple hydrogen-bonding interactions involving the nitroimidazolium cation and the chloride anion. Strong hydrogen bonds between the amine hydrogen atom and the chloride anion link the ionic moieties. Of note, with respect to H⋯Cl interactions, the central aromatic hydrogen atom displays a shorter interaction than the other aromatic hydrogen atom. Finally, interactions are observed between the nitro moiety and methyl H atoms. While no π–π stacking is observed, anion-π interactions are present. The crystal was refined as a two-component twin.
Keywords: crystal structure; imidazolium; π-hole; hydrogen bonding.
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-nitroimidazole-based pharmaceuticals (Bowden & Izadi, 1998). Furthermore, Miyamoto and coworkers reported the synthesis of a new class of nitroimidazole derivatives to combat drug-resistant strains of infections (Miyamoto et al., 2013). Hence, with the renewed interest in 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 & Trzybiński, 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., π-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 π-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 anti-solvent. Colorless crystals of the hydrolyzed byproduct reported herein were observed within one week.
For full experimental details including crystal data, data collection and structure refinement details, refer to Table 2.
The structure emulates a double the volume orthorhombic C-centered cell and is twinned by this symmetry (180° rotation around the real space a axis or around the reciprocal direction ). Refinement with the transformation matrix 1 0 0, 0 −1 0, −1 0 −1 yielded a 0.555 (1) to 0.445 (1) twinning ratio.
Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314622008781/tk4083sup1.cif
Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314622008781/tk4083Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2414314622008781/tk4083Isup3.cml
Data collection: APEX3 (Bruker, 2019); cell refinement: SAINT (Bruker, 2019); data reduction: SAINT (Bruker, 2019); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015) ShelXle (Hübschle et al., 2011); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009), publCIF (Westrip, 2010), CSD (Groom et al., 2016), enCIFer (Allen et al., 2004).
|C4H6N3O2+·Cl−||F(000) = 336|
|Mr = 163.57||Dx = 1.549 Mg m−3|
|Monoclinic, P21/c||Mo Kα radiation, λ = 0.71073 Å|
|a = 6.3498 (5) Å||Cell parameters from 9893 reflections|
|b = 9.8991 (9) Å||θ = 2.8–33.2°|
|c = 11.5969 (10) Å||µ = 0.49 mm−1|
|β = 105.817 (3)°||T = 150 K|
|V = 701.35 (10) Å3||Rod, colourless|
|Z = 4||0.35 × 0.15 × 0.12 mm|
|Bruker AXS D8 Quest |
diffractometer with PhotonII charge-integrating pixel array detector (CPAD)
|2556 reflections with I > 2σ(I)|
|Detector resolution: 7.4074 pixels mm-1||Rint = 0.037|
|ω and phi scans||θmax = 33.3°, θmin = 2.8°|
|Absorption correction: multi-scan |
(SADABS; Krause et al., 2015)
|h = −8→9|
|Tmin = 0.659, Tmax = 0.747||k = −15→14|
|12789 measured reflections||l = −16→17|
|2681 independent reflections|
|Refinement on F2||Primary atom site location: structure-invariant direct methods|
|Least-squares matrix: full||Secondary atom site location: difference Fourier map|
|R[F2 > 2σ(F2)] = 0.026||Hydrogen site location: mixed|
|wR(F2) = 0.072||H atoms treated by a mixture of independent and constrained refinement|
|S = 1.08|| w = 1/[σ2(Fo2) + (0.039P)2 + 0.1001P] |
where P = (Fo2 + 2Fc2)/3
|2681 reflections||(Δ/σ)max = 0.001|
|97 parameters||Δρmax = 0.35 e Å−3|
|0 restraints||Δρmin = −0.24 e Å−3|
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.
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 Uiso(H) = 1.2 × Ueq(C), and to 0.98 Å for CH3 moieties with Uiso(H) = 1.5 × Ueq(C). The N—H proton on N3 was located as residual electron density and allowed to refine freely.
|Cl1||0.75167 (5)||0.72586 (3)||0.07499 (2)||0.02027 (7)|
|O1||−0.1250 (2)||0.37864 (11)||0.13424 (9)||0.0313 (2)|
|O2||−0.14844 (16)||0.45993 (11)||0.30478 (8)||0.02609 (19)|
|N3||0.42357 (17)||0.61303 (11)||0.19454 (9)||0.02019 (19)|
|H3||0.512 (3)||0.6439 (18)||0.1567 (14)||0.019 (4)*|
|N1||0.25774 (17)||0.58619 (10)||0.33532 (8)||0.01734 (17)|
|N4||−0.05494 (18)||0.44564 (10)||0.22517 (8)||0.01998 (18)|
|C5||0.14730 (19)||0.51334 (11)||0.23575 (9)||0.01723 (18)|
|C4||0.2514 (2)||0.53027 (13)||0.14779 (10)||0.0202 (2)|
|C2||0.4252 (2)||0.64545 (12)||0.30717 (10)||0.0202 (2)|
|C6||0.2176 (2)||0.59302 (13)||0.45524 (10)||0.0224 (2)|
|Cl1||0.02085 (12)||0.01942 (11)||0.02158 (11)||−0.00029 (9)||0.00752 (10)||0.00269 (9)|
|O1||0.0386 (6)||0.0293 (5)||0.0243 (4)||−0.0130 (4)||0.0060 (4)||−0.0054 (3)|
|O2||0.0224 (4)||0.0351 (5)||0.0225 (4)||−0.0009 (4)||0.0090 (3)||0.0033 (3)|
|N3||0.0207 (4)||0.0232 (5)||0.0186 (4)||0.0012 (4)||0.0086 (4)||0.0026 (3)|
|N1||0.0206 (4)||0.0166 (4)||0.0161 (4)||−0.0004 (3)||0.0071 (3)||−0.0011 (3)|
|N4||0.0217 (4)||0.0195 (4)||0.0182 (4)||−0.0011 (4)||0.0045 (3)||0.0033 (3)|
|C5||0.0194 (5)||0.0169 (4)||0.0152 (4)||0.0010 (4)||0.0044 (4)||0.0010 (3)|
|C4||0.0223 (5)||0.0229 (5)||0.0160 (4)||0.0016 (4)||0.0060 (4)||0.0014 (4)|
|C2||0.0214 (5)||0.0200 (5)||0.0199 (5)||−0.0011 (4)||0.0068 (4)||−0.0001 (4)|
|C6||0.0306 (6)||0.0232 (5)||0.0162 (4)||−0.0047 (4)||0.0110 (4)||−0.0038 (4)|
|O1—N4||1.2223 (14)||N4—C5||1.4239 (16)|
|O2—N4||1.2343 (13)||C5—C4||1.3687 (16)|
|C4—N3—H3||125.4 (11)||N3—C4—C5||106.06 (10)|
|C2—N1—C5||106.44 (10)||N1—C2—N3||109.79 (11)|
|O1—N4—C5—N1||−175.66 (11)||C4—N3—C2—N1||−0.17 (14)|
|O1—N4—C5—C4||11.97 (18)||C2—N3—C4—C5||0.12 (14)|
|O2—N4—C5—N1||5.77 (16)||C2—N1—C5—N4||−173.64 (11)|
|O2—N4—C5—C4||−166.59 (12)||C2—N1—C5—C4||−0.08 (13)|
|N1—C5—C4—N3||−0.02 (13)||C6—N1—C5—N4||10.81 (18)|
|N4—C5—C4—N3||173.29 (11)||C6—N1—C5—C4||−175.63 (11)|
|C5—N1—C2—N3||0.15 (13)||C6—N1—C2—N3||175.98 (10)|
|N3—H3···Cl1||0.856 (19)||2.160 (19)||3.0141 (11)||175.4 (15)|
|Symmetry codes: (i) −x+1, −y+1, −z; (ii) x, −y+3/2, z+1/2; (iii) −x+1, y−1/2, −z+1/2.|
AM thanks the National Institute of Health for the financial support (grant No. 1R21GM142011–01 A1). PCH would like to thank Florida Gulf Coast University Department of Chemistry and Physics for the use of their instruments in supporting this work. SB and PCH would like to thank Michael & Lisa Schwartz for their generous financial support of undergraduate research at AMU.
Funding for this research was provided by: National Institutes of Health (grant No. 1R21GM142011-01A1); National Science Foundation (grant No. CHE-1625543; grant No. CHE–1952846); Ave Maria University Department of Chemistry and Physics.
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