organic compounds
Ethyl 2-(2-methyl-4-nitro-1H-imidazol-1-yl)acetate
aLaboratoire de Chimie Organique et Analytique, Université Sultan Moulay Slimane, Faculté des Sciences et Techniques, Béni-Mellal, BP 523, Morocco, and bLaboratoire de Chimie du Solide Appliquée, Faculty of Sciences, Mohammed V University in Rabat, Avenue Ibn Battouta, BP 1014, Rabat, Morocco
*Correspondence e-mail: yhakmaoui1@gmail.com
In the title compound, C8H11N3O4, the imidazole ring and the nitro group are nearly coplanar, with the largest deviation from the mean plane being 0.119 (2) Å. The mean plane through the acetate group is approximately perpendicular to the imidazole ring, subtending a dihedral angle of 75.71 (13)°. In the crystal, molecules are linked by weak C—H⋯O and very weak C—H⋯N hydrogen bonds, forming a three-dimensional network. There is also a weak C—H⋯π(imidazole) interaction, which contributes to the stability of the crystal packing arrangement.
Keywords: crystals structure; nitro-1H-imidazole; acetate; hydrogen bonds.
CCDC reference: 1473028
Structure description
Imidazoles are an important class of et al., 2014; Adamovich et al., 2014). Some nitroimidazole derivatives have been identified as notable radiosensitizers, antiprotozoal, antifungal and antibacterial or anti-epileptic agents (Olender et al., 2009; Duan et al., 2014; Sutherland et al., 2010).
that are abundant in the structures of many natural and synthetic pharmacologically active substances (NeildéThe molecule of the title compound is build up from a nitro- and methyl-substituted imidazole ring (C1–C3/N2/N3) linked to an ethylacetate moiety, as shown in Fig. 1. The nitro group and the imidazole ring are coplanar with a maximum deviation from the mean plane of 0.119 (2) Å for O1. The imidazole ring makes a dihedral angle of 75.71 (13)° with the plane through the acetate group. The title compound is achiral, although it crystallizes in a chiral space group.
The ). There is also a weak C5—H5A⋯π interaction, which contributes to the stability of the crystal packing arrangement, as shown in Fig. 2.
cohesion is ensured by C—H⋯O and C—H⋯N hydrogen-bonding interactions (Table 1Synthesis and crystallization
To a solution of 2-methyl-5-nitro-1H-imidazole (7.87 mmol) in DMSO was added potassium hydroxide (8.7 mmol). After 15 min of stirring at 298 K, ethyl bromoacetate (15.74 mmol) was added dropwise. Upon disappearance of the starting material as indicated by TLC, the mixture was added to ice–water and extracted with ethyl acetate. The organic phase was washed with brine and dried over magnesium sulfate. The solvent was evaporated in vacuo. The resulting residue was purified by (EtOAc/hexane 09/01). The title compound was recrystallized from ethanol at room temperature giving colourless crystals (m.p. 351 K, yield 68%).
Refinement
Crystal data, data collection and structure .
details are summarized in Table 2Structural data
CCDC reference: 1473028
10.1107/S2414314616005885/zp4004sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S2414314616005885/zp4004Isup2.hkl
Supporting information file. DOI: 10.1107/S2414314616005885/zp4004Isup3.cml
To a solution of 2-methyl-5-nitro-1H-imidazole (7.87 mmol) in DMSO was added potassium hydroxide (8.7 mmol). After 15 min of stirring at 298 K, ethyl bromoacetate (15.74 mmol) was added dropwise. Upon disappearance of the starting material as indicated by TLC, the mixture was added to ice–water and extracted with ethyl acetate. The organic phase was washed with brine and dried over magnesium sulfate. The solvent was evaporated in vacuo. The resulting residue was purified by
(EtOAc/hexane 09/01). The title compound was recrystallized from ethanol at room temperature giving colourless crystals (m.p. 351 K, yield 68%).Imidazoles are an important class of
that are abundant in the structures of many natural and synthetic pharmacologically active substances (Neildé et al., 2014; Adamovich et al., 2014). Some nitroimidazole derivatives have been identified as notable radiosensitizers, antiprotozoal, antifungal and antibacterial or anti-epileptic agents (Olender et al., 2009; Duan et al., 2014; Sutherland et al., 2010).The molecule of the title compound is build up from anitro- and methyl-substituted imidazole ring (C1–C3/N2/N3) linked to an ethylacetate moiety, as shown in Fig.1. The nitro group and the imidazole ring are coplanar with a maximum deviation from the mean plane of 0.119 (2) Å for O1. The imidazole ring makes a dihedral angle of 75.71 (13)° with the plane through the acetate group. The title compound is achiral, although it crystallizes in a chiral space group.
The π interaction, which contributes to the stability of the crystal packing arrangement, as shown in Fig. 2.
cohesion is ensured by C—H···O and C—H···N hydrogen-bonding interactions (Table 1). There is also a weak C5—H5A···Data collection: APEX2 (Bruker, 2009); cell
SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXS2014 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: ORTEPIII (Burnett & Johnson, 1996) and ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: publCIF (Westrip, 2010).Fig. 1. Plot of the molecule of the title compound, showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are represented as small circles. | |
Fig. 2. The crystal packing for the title compound, showing hydrogen bonds as dashed lines. |
C8H11N3O4 | Dx = 1.415 Mg m−3 |
Mr = 213.20 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, P212121 | Cell parameters from 2802 reflections |
a = 4.4793 (2) Å | θ = 2.2–29.6° |
b = 10.3596 (5) Å | µ = 0.12 mm−1 |
c = 21.5724 (11) Å | T = 296 K |
V = 1001.04 (8) Å3 | Block, colourless |
Z = 4 | 0.13 × 0.12 × 0.10 mm |
F(000) = 448 |
Bruker X8 APEX diffractometer | 2802 independent reflections |
Radiation source: fine-focus sealed tube | 2488 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.040 |
φ and ω scans | θmax = 29.6°, θmin = 2.2° |
Absorption correction: multi-scan (SADABS; Bruker, 2009) | h = −6→6 |
Tmin = 0.635, Tmax = 0.746 | k = −11→14 |
23416 measured reflections | l = −29→29 |
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)] = 0.037 | Hydrogen site location: difference Fourier map |
wR(F2) = 0.100 | H-atom parameters constrained |
S = 1.06 | w = 1/[σ2(Fo2) + (0.0574P)2 + 0.0658P] where P = (Fo2 + 2Fc2)/3 |
2802 reflections | (Δ/σ)max < 0.001 |
137 parameters | Δρmax = 0.18 e Å−3 |
0 restraints | Δρmin = −0.15 e Å−3 |
C8H11N3O4 | V = 1001.04 (8) Å3 |
Mr = 213.20 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 4.4793 (2) Å | µ = 0.12 mm−1 |
b = 10.3596 (5) Å | T = 296 K |
c = 21.5724 (11) Å | 0.13 × 0.12 × 0.10 mm |
Bruker X8 APEX diffractometer | 2802 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2009) | 2488 reflections with I > 2σ(I) |
Tmin = 0.635, Tmax = 0.746 | Rint = 0.040 |
23416 measured reflections |
R[F2 > 2σ(F2)] = 0.037 | 0 restraints |
wR(F2) = 0.100 | H-atom parameters constrained |
S = 1.06 | Δρmax = 0.18 e Å−3 |
2802 reflections | Δρmin = −0.15 e Å−3 |
137 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.6714 (4) | 0.89444 (15) | 0.23607 (7) | 0.0340 (3) | |
C2 | 0.8179 (4) | 0.78660 (15) | 0.25496 (7) | 0.0357 (4) | |
H2 | 0.8107 | 0.7045 | 0.2376 | 0.043* | |
C3 | 0.9159 (4) | 0.95500 (14) | 0.31441 (8) | 0.0351 (4) | |
C4 | 1.0510 (5) | 1.03126 (19) | 0.36538 (9) | 0.0512 (5) | |
H4A | 1.0123 | 0.9894 | 0.4043 | 0.077* | |
H4B | 0.9655 | 1.1162 | 0.3658 | 0.077* | |
H4C | 1.2626 | 1.0375 | 0.3590 | 0.077* | |
C5 | 1.1594 (4) | 0.74202 (18) | 0.34365 (8) | 0.0395 (4) | |
H5A | 1.3374 | 0.7879 | 0.3567 | 0.047* | |
H5B | 1.2214 | 0.6676 | 0.3196 | 0.047* | |
C6 | 0.9893 (4) | 0.69707 (15) | 0.40023 (8) | 0.0346 (3) | |
C8 | 0.9589 (6) | 0.53412 (19) | 0.47602 (9) | 0.0541 (5) | |
H8A | 0.7444 | 0.5356 | 0.4698 | 0.065* | |
H8B | 1.0053 | 0.5821 | 0.5134 | 0.065* | |
C9 | 1.0674 (7) | 0.3982 (2) | 0.48146 (12) | 0.0703 (7) | |
H9A | 0.9722 | 0.3572 | 0.5161 | 0.105* | |
H9B | 1.0201 | 0.3519 | 0.4442 | 0.105* | |
H9C | 1.2797 | 0.3982 | 0.4876 | 0.105* | |
N1 | 0.4717 (4) | 0.90250 (14) | 0.18451 (7) | 0.0422 (3) | |
N2 | 0.7284 (4) | 0.99894 (13) | 0.27239 (6) | 0.0371 (3) | |
N3 | 0.9776 (3) | 0.82629 (12) | 0.30513 (6) | 0.0338 (3) | |
O1 | 0.3344 (4) | 1.00273 (14) | 0.17624 (8) | 0.0603 (4) | |
O2 | 0.4468 (5) | 0.80706 (15) | 0.15122 (7) | 0.0671 (5) | |
O3 | 0.7749 (3) | 0.75150 (13) | 0.42096 (6) | 0.0492 (3) | |
O4 | 1.1105 (3) | 0.59101 (12) | 0.42288 (6) | 0.0421 (3) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0341 (8) | 0.0307 (7) | 0.0370 (7) | 0.0001 (7) | 0.0003 (7) | 0.0044 (6) |
C2 | 0.0422 (9) | 0.0287 (7) | 0.0364 (7) | 0.0035 (7) | 0.0022 (7) | 0.0001 (6) |
C3 | 0.0386 (9) | 0.0282 (7) | 0.0385 (8) | 0.0003 (7) | 0.0017 (7) | 0.0029 (6) |
C4 | 0.0637 (13) | 0.0421 (9) | 0.0479 (9) | −0.0055 (10) | −0.0087 (10) | −0.0026 (8) |
C5 | 0.0324 (8) | 0.0418 (8) | 0.0443 (8) | 0.0106 (7) | −0.0010 (7) | 0.0077 (7) |
C6 | 0.0312 (8) | 0.0336 (7) | 0.0389 (7) | −0.0008 (7) | −0.0065 (7) | 0.0009 (6) |
C8 | 0.0583 (13) | 0.0524 (11) | 0.0515 (10) | −0.0075 (10) | 0.0016 (10) | 0.0146 (8) |
C9 | 0.0853 (19) | 0.0504 (12) | 0.0753 (15) | −0.0096 (13) | −0.0046 (14) | 0.0242 (11) |
N1 | 0.0408 (8) | 0.0410 (7) | 0.0449 (7) | −0.0039 (7) | −0.0071 (7) | 0.0092 (6) |
N2 | 0.0407 (8) | 0.0291 (6) | 0.0414 (7) | 0.0036 (6) | −0.0004 (6) | 0.0021 (5) |
N3 | 0.0341 (7) | 0.0305 (6) | 0.0367 (6) | 0.0070 (6) | 0.0007 (6) | 0.0031 (5) |
O1 | 0.0571 (10) | 0.0531 (8) | 0.0706 (9) | 0.0089 (8) | −0.0214 (8) | 0.0145 (7) |
O2 | 0.0850 (13) | 0.0544 (8) | 0.0619 (8) | −0.0040 (9) | −0.0289 (9) | −0.0058 (7) |
O3 | 0.0453 (7) | 0.0503 (7) | 0.0521 (7) | 0.0101 (7) | 0.0084 (6) | 0.0035 (6) |
O4 | 0.0387 (6) | 0.0392 (6) | 0.0485 (7) | 0.0011 (5) | −0.0035 (6) | 0.0120 (5) |
C1—C2 | 1.358 (2) | C5—H5A | 0.9700 |
C1—N2 | 1.360 (2) | C5—H5B | 0.9700 |
C1—N1 | 1.430 (2) | C6—O3 | 1.200 (2) |
C2—N3 | 1.361 (2) | C6—O4 | 1.3194 (19) |
C2—H2 | 0.9300 | C8—O4 | 1.457 (2) |
C3—N2 | 1.317 (2) | C8—C9 | 1.494 (3) |
C3—N3 | 1.3764 (19) | C8—H8A | 0.9700 |
C3—C4 | 1.483 (2) | C8—H8B | 0.9700 |
C4—H4A | 0.9600 | C9—H9A | 0.9600 |
C4—H4B | 0.9600 | C9—H9B | 0.9600 |
C4—H4C | 0.9600 | C9—H9C | 0.9600 |
C5—N3 | 1.455 (2) | N1—O1 | 1.2200 (19) |
C5—C6 | 1.512 (2) | N1—O2 | 1.227 (2) |
C2—C1—N2 | 113.02 (14) | O3—C6—C5 | 124.00 (15) |
C2—C1—N1 | 125.71 (15) | O4—C6—C5 | 110.36 (14) |
N2—C1—N1 | 121.26 (14) | O4—C8—C9 | 106.94 (19) |
C1—C2—N3 | 104.13 (14) | O4—C8—H8A | 110.3 |
C1—C2—H2 | 127.9 | C9—C8—H8A | 110.3 |
N3—C2—H2 | 127.9 | O4—C8—H8B | 110.3 |
N2—C3—N3 | 111.28 (15) | C9—C8—H8B | 110.3 |
N2—C3—C4 | 125.90 (15) | H8A—C8—H8B | 108.6 |
N3—C3—C4 | 122.82 (16) | C8—C9—H9A | 109.5 |
C3—C4—H4A | 109.5 | C8—C9—H9B | 109.5 |
C3—C4—H4B | 109.5 | H9A—C9—H9B | 109.5 |
H4A—C4—H4B | 109.5 | C8—C9—H9C | 109.5 |
C3—C4—H4C | 109.5 | H9A—C9—H9C | 109.5 |
H4A—C4—H4C | 109.5 | H9B—C9—H9C | 109.5 |
H4B—C4—H4C | 109.5 | O1—N1—O2 | 123.66 (16) |
N3—C5—C6 | 111.33 (14) | O1—N1—C1 | 118.61 (15) |
N3—C5—H5A | 109.4 | O2—N1—C1 | 117.72 (16) |
C6—C5—H5A | 109.4 | C3—N2—C1 | 103.94 (13) |
N3—C5—H5B | 109.4 | C2—N3—C3 | 107.62 (14) |
C6—C5—H5B | 109.4 | C2—N3—C5 | 124.56 (13) |
H5A—C5—H5B | 108.0 | C3—N3—C5 | 127.64 (15) |
O3—C6—O4 | 125.64 (17) | C6—O4—C8 | 115.87 (15) |
Cg is the centroid of the imidazole ring. |
D—H···A | D—H | H···A | D···A | D—H···A |
C5—H5A···O3i | 0.97 | 2.43 | 3.224 (2) | 139 |
C8—H8B···O3ii | 0.97 | 2.54 | 3.446 (3) | 156 |
C5—H5B···N2iii | 0.97 | 2.65 | 3.586 (2) | 161 |
C5—H5B···O1iii | 0.97 | 2.62 | 3.387 (2) | 136 |
C5—H5A···Cgi | 0.97 | 2.98 | 3.651 (2) | 128 |
Symmetry codes: (i) x+1, y, z; (ii) x+1/2, −y+3/2, −z+1; (iii) −x+2, y−1/2, −z+1/2. |
Cg is the centroid of the imidazole ring. |
D—H···A | D—H | H···A | D···A | D—H···A |
C5—H5A···O3i | 0.97 | 2.43 | 3.224 (2) | 138.8 |
C8—H8B···O3ii | 0.97 | 2.54 | 3.446 (3) | 156.1 |
C5—H5B···N2iii | 0.97 | 2.65 | 3.586 (2) | 161.4 |
C5—H5B···O1iii | 0.97 | 2.62 | 3.387 (2) | 135.7 |
C5—H5A···Cgi | 0.97 | 2.98 | 3.651 (2) | 128 |
Symmetry codes: (i) x+1, y, z; (ii) x+1/2, −y+3/2, −z+1; (iii) −x+2, y−1/2, −z+1/2. |
Experimental details
Crystal data | |
Chemical formula | C8H11N3O4 |
Mr | 213.20 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 296 |
a, b, c (Å) | 4.4793 (2), 10.3596 (5), 21.5724 (11) |
V (Å3) | 1001.04 (8) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.12 |
Crystal size (mm) | 0.13 × 0.12 × 0.10 |
Data collection | |
Diffractometer | Bruker X8 APEX |
Absorption correction | Multi-scan (SADABS; Bruker, 2009) |
Tmin, Tmax | 0.635, 0.746 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 23416, 2802, 2488 |
Rint | 0.040 |
(sin θ/λ)max (Å−1) | 0.694 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.037, 0.100, 1.06 |
No. of reflections | 2802 |
No. of parameters | 137 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.18, −0.15 |
Computer programs: APEX2 (Bruker, 2009), SAINT (Bruker, 2009), SHELXS2014 (Sheldrick, 2008), SHELXL2014 (Sheldrick, 2015), ORTEPIII (Burnett & Johnson, 1996) and ORTEP-3 for Windows (Farrugia, 2012), publCIF (Westrip, 2010).
Acknowledgements
The authors thank the Unit of Support for Technical and Scientific Research (UATRS, CNRST) for the X-ray measurements and the University Sultan Moulay Slimane, Beni-Mellal, Morocco, for financial support.
References
Adamovich, S. N., Ushakov, I. A., Mirskova, A. N., Mirskov, R. G. & Voronov, V. K. (2014). Mendeleev Commun. 24, 293–294. Web of Science CrossRef CAS Google Scholar
Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Burnett, M. N. & Johnson, C. K. (1996). ORTEPIII. Report ORNL-6895. Oak Ridge National Laboratory, Tennessee, USA. Google Scholar
Duan, Y.-T., Wang, Z.-C., Sang, Y.-L., Tao, X.-X., Teraiya, S. B., Wang, P.-F., Wen, Q., Zhou, X.-J., Ding, L., Yang, Y.-H. & Zhu, H.-L. (2014). Eur. J. Med. Chem. 76, 387–396. Web of Science CSD CrossRef CAS PubMed Google Scholar
Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854. Web of Science CrossRef CAS IUCr Journals Google Scholar
Neildé, K., Crozet, M. D., Terme, T. & Vanelle, P. (2014). Tetrahedron Lett. 55, 3652–3657. Google Scholar
Olender, D., Żwawiak, J., Lukianchuk, V., Lesyk, R., Kropacz, A., Fojutowski, A. & Zaprutko, L. (2009). Eur. J. Med. Chem. 44, 645–652. Web of Science CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2015). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sutherland, H. S., Blaser, A., Kmentova, I., Franzblau, S. G., Wan, B., Wang, Y., Ma, Z., Palmer, B. D., Denny, W. A. & Thompson, A. M. (2010). J. Med. Chem. 53, 855–866. Web of Science CrossRef PubMed CAS Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar
This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.