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Acta Crystallogr Sect E Struct Rep Online. 2010 March 1; 66(Pt 3): o548.
Published online 2010 February 6. doi:  10.1107/S1600536810004186
PMCID: PMC2983685

2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl 2-nitro­benzoate

Abstract

In the title compound, C13H12N4O6, the mean plane through the nitro­benzene forms a dihedral angle of 37.38 (15)° with the plane through the imidazole ring. The crystal packing is stabilized by weak inter­molecular C—H(...)O and C—H(...)N inter­actions together with π–π stacking inter­actions between nitro­benzene rings [centroid–centroid distance = 3.788 (3) Å] and between imidazole rings [centroid–centroid distance = 3.590 (2) Å].

Related literature

For the pharmacological uses of metronidazole, see: Mao et al. (2009 [triangle]); Cosar et al. (1966 [triangle]); Bowden & Izadi (1997 [triangle]). For a related structure, see: Bahadur et al. (2009 [triangle]). For additional structural analysis, see: Spek (2009 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-0o548-scheme1.jpg

Experimental

Crystal data

  • C13H12N4O6
  • M r = 320.27
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-0o548-efi1.jpg
  • a = 15.392 (8) Å
  • b = 8.605 (4) Å
  • c = 10.968 (5) Å
  • β = 106.576 (9)°
  • V = 1392.3 (12) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.12 mm−1
  • T = 150 K
  • 0.27 × 0.24 × 0.08 mm

Data collection

  • Bruker APEX 2000 CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 1997 [triangle]) T min = 0.573, T max = 0.969
  • 9743 measured reflections
  • 2444 independent reflections
  • 1700 reflections with I > \2s(I)
  • R int = 0.099

Refinement

  • R[F 2 > 2σ(F 2)] = 0.056
  • wR(F 2) = 0.129
  • S = 1.00
  • 2444 reflections
  • 209 parameters
  • H-atom parameters constrained
  • Δρmax = 0.23 e Å−3
  • Δρmin = −0.23 e Å−3

Data collection: SMART (Bruker, 2001 [triangle]); cell refinement: SAINT (Bruker, 2001 [triangle]); data reduction: SHELXTL (Sheldrick, 2008 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810004186/tk2618sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810004186/tk2618Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

The authors thank the Pakistan Science Foundation for financial support.

supplementary crystallographic information

Comment

Metronidazole,1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole, is an antibiotic which is effective against anaerobic bacteria and certain parasites (Mao et al., 2009). However, there are problems related to its low aqueous solubility, toxicity and poor absorption characteristics (Bowden & Izadi 1997). In order to improve the water-solubility of metronidazole, certain esters and hemi-esters of metronidazole have been prepared (Cosar et al., 1966) which have shown better solubility in aqueous medium compared to the parent metronidazole. Here, we are reporting the synthesis and crystal structure of an ester derivative of metronidazole, (I).

The molecule of (I), Fig. 1, is non-planar with a dihedral angle of 37.38 (15) ° formed between the mean planes through the nitrobenzene and imidazole rings (Spek, 2009). The nitro group is co-planar with the imidazole ring to which it is connected [dihedral angle 0.90 (3) °] , while the phenyl-nitro group is slightly twisted out of the plane of the benzene ring, forming a dihedral angle of 8.13 (3) °. The key C═O and C—N bond distances are in agreement with those observed in the related structure of 2-(2-methyl-5-nitro-1 H-imidazol-1-yl) ethyl 3-bromobenzoate (Bahadur et al., 2009). The crystal packing is stabilized by weak intermolecular C—H···O and C—H···N interactions, Table 1 , together with π-π stacking interactions with the shortest of these occuring between symmetry related imidazole rings [ring centroid (N1–C12)··· ring centroid (N1–C12)i =3.590 (2) Å for ii: 1-x, -y, 1-z]. In addition, π···π contacts are noted between symmetry related nitrobenzene rings [ring centroid (C2–C7)···ring centroid (C2–C7)ii = 3.788 (3) Å for ii : 1-x, 2-y, 1-z].

Experimental

Metronidazole (5 g, 29.23 mmol) was added to 4-nitrobenzoic acid (9.38 g, 56.11 mmol) dissolved in anhydrous CH2Cl2 (10 ml). Then, 4-dimethylaminopyridine (0.15 equiv.) and dicyclohexylcarbodiimide (1.25 equiv) were added, and the resulting solution stirred. After 12 h, the solvent was evaporated under reduced pressure. The crude reaction mixture was subjected to flash column chromatography over silica gel, successively eluting with n-hexane–ethyl acetate (2.8: 7.2) which afforded (I) in 73 % yield. Colorless crystals were obtained from the slow evaporation of a CH2Cl2 solution of (I).

Refinement

The C-bound H atoms were geometrically placed (C–H = 0.95–0.99 Å) and refined as riding with Uiso(H) = 1.2–1.5Ueq(C).

Figures

Fig. 1.
Molecular Structure of (I) with atom labelling scheme and 30% probability displacement ellipsoids.

Crystal data

C13H12N4O6F(000) = 664
Mr = 320.27Dx = 1.528 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 721 reflections
a = 15.392 (8) Åθ = 2.8–23.3°
b = 8.605 (4) ŵ = 0.12 mm1
c = 10.968 (5) ÅT = 150 K
β = 106.576 (9)°Plate, yellow
V = 1392.3 (12) Å30.27 × 0.24 × 0.08 mm
Z = 4

Data collection

Bruker APEX 2000 CCD area-detector diffractometer2444 independent reflections
Radiation source: fine-focus sealed tube1700 reflections with I > \2s(I)
graphiteRint = 0.099
[var phi] and ω scansθmax = 25.0°, θmin = 1.4°
Absorption correction: multi-scan (SADABS; Sheldrick, 1997)h = −18→18
Tmin = 0.573, Tmax = 0.969k = −10→10
9743 measured reflectionsl = −13→12

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.056Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.129H-atom parameters constrained
S = 1.00w = 1/[σ2(Fo2) + (0.0572P)2] where P = (Fo2 + 2Fc2)/3
2444 reflections(Δ/σ)max < 0.001
209 parametersΔρmax = 0.23 e Å3
0 restraintsΔρmin = −0.23 e Å3

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.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
O10.23596 (12)0.70542 (19)0.54231 (16)0.0328 (5)
O20.09150 (14)0.6281 (2)0.5020 (2)0.0531 (6)
O30.17653 (15)0.8476 (3)0.73301 (19)0.0554 (6)
O40.17995 (15)1.0918 (3)0.7714 (2)0.0678 (7)
O50.33567 (14)0.2348 (2)0.51061 (18)0.0456 (6)
O60.35085 (16)0.1756 (2)0.3260 (2)0.0535 (6)
N10.38462 (14)0.5437 (2)0.47700 (18)0.0274 (5)
N20.42041 (15)0.6345 (3)0.3073 (2)0.0349 (6)
N30.16552 (16)0.9819 (3)0.6976 (2)0.0429 (6)
N40.35352 (16)0.2691 (3)0.4118 (2)0.0359 (6)
C10.14715 (19)0.7286 (3)0.5095 (2)0.0335 (6)
C20.12371 (17)0.8940 (3)0.4747 (3)0.0336 (7)
C30.13293 (17)1.0152 (3)0.5613 (3)0.0342 (7)
C40.10931 (18)1.1655 (3)0.5259 (3)0.0419 (8)
H40.11701.24490.58820.050*
C50.0745 (2)1.1999 (4)0.3993 (3)0.0490 (8)
H50.05761.30350.37320.059*
C60.0642 (2)1.0840 (4)0.3104 (3)0.0500 (8)
H60.03951.10760.22270.060*
C70.08938 (19)0.9331 (4)0.3477 (3)0.0434 (7)
H70.08300.85460.28480.052*
C80.26654 (18)0.5514 (3)0.5882 (2)0.0327 (6)
H8A0.23390.47170.52720.039*
H8B0.25520.53230.67130.039*
C90.36572 (17)0.5446 (3)0.6016 (2)0.0287 (6)
H9A0.39590.63540.65140.034*
H9B0.39150.44950.64920.034*
C100.40945 (17)0.6699 (3)0.4201 (2)0.0306 (6)
C110.40087 (18)0.4813 (3)0.2895 (2)0.0351 (7)
H110.40190.42310.21630.042*
C120.37939 (18)0.4234 (3)0.3933 (2)0.0299 (6)
C130.4210 (2)0.8282 (3)0.4750 (3)0.0405 (7)
H13A0.45100.89420.42640.061*
H13B0.45820.82320.56380.061*
H13C0.36150.87180.47120.061*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0350 (11)0.0268 (10)0.0376 (11)0.0009 (8)0.0123 (9)0.0037 (8)
O20.0401 (12)0.0407 (13)0.0799 (16)−0.0053 (10)0.0196 (11)0.0035 (11)
O30.0745 (16)0.0549 (16)0.0435 (14)0.0126 (12)0.0276 (12)0.0088 (11)
O40.0684 (17)0.0673 (17)0.0586 (15)0.0159 (13)0.0036 (13)−0.0246 (13)
O50.0764 (16)0.0276 (11)0.0378 (12)−0.0041 (10)0.0242 (11)0.0047 (9)
O60.0910 (18)0.0274 (11)0.0468 (13)−0.0035 (11)0.0272 (12)−0.0119 (10)
N10.0364 (13)0.0205 (12)0.0267 (12)0.0006 (9)0.0109 (10)0.0008 (9)
N20.0456 (14)0.0312 (14)0.0310 (13)0.0002 (11)0.0159 (11)0.0028 (10)
N30.0360 (14)0.0465 (17)0.0478 (17)0.0069 (12)0.0143 (12)−0.0085 (14)
N40.0512 (15)0.0251 (13)0.0329 (14)0.0018 (11)0.0144 (12)−0.0017 (11)
C10.0320 (16)0.0359 (17)0.0340 (16)−0.0031 (13)0.0115 (13)−0.0009 (13)
C20.0281 (15)0.0340 (16)0.0417 (17)−0.0003 (12)0.0147 (13)0.0030 (13)
C30.0250 (14)0.0397 (18)0.0394 (17)0.0017 (12)0.0115 (12)−0.0014 (13)
C40.0341 (17)0.0337 (17)0.061 (2)0.0015 (13)0.0191 (15)−0.0012 (15)
C50.0392 (18)0.0387 (19)0.072 (2)0.0058 (14)0.0208 (17)0.0174 (18)
C60.0432 (19)0.059 (2)0.0473 (19)0.0058 (16)0.0127 (15)0.0210 (18)
C70.0394 (18)0.0483 (19)0.0446 (19)0.0006 (15)0.0155 (15)0.0031 (15)
C80.0459 (17)0.0227 (14)0.0334 (15)0.0011 (12)0.0177 (13)0.0017 (11)
C90.0422 (16)0.0215 (14)0.0247 (14)0.0032 (12)0.0134 (12)0.0015 (11)
C100.0365 (16)0.0220 (15)0.0345 (16)0.0023 (12)0.0122 (12)0.0060 (12)
C110.0459 (18)0.0310 (17)0.0311 (16)0.0018 (13)0.0151 (13)−0.0024 (12)
C120.0425 (17)0.0200 (14)0.0285 (14)0.0023 (12)0.0120 (12)−0.0020 (11)
C130.0504 (19)0.0251 (16)0.0480 (18)−0.0049 (13)0.0172 (15)0.0009 (13)

Geometric parameters (Å, °)

O1—C11.326 (3)C4—C51.370 (4)
O1—C81.448 (3)C4—H40.9500
O2—C11.204 (3)C5—C61.371 (4)
O3—N31.216 (3)C5—H50.9500
O4—N31.223 (3)C6—C71.384 (4)
O5—N41.227 (3)C6—H60.9500
O6—N41.230 (3)C7—H70.9500
N1—C101.360 (3)C8—C91.492 (4)
N1—C121.371 (3)C8—H8A0.9900
N1—C91.476 (3)C8—H8B0.9900
N2—C101.331 (3)C9—H9A0.9900
N2—C111.354 (3)C9—H9B0.9900
N3—C31.462 (4)C10—C131.479 (4)
N4—C121.417 (3)C11—C121.367 (3)
C1—C21.491 (4)C11—H110.9500
C2—C71.383 (4)C13—H13A0.9800
C2—C31.390 (4)C13—H13B0.9800
C3—C41.369 (4)C13—H13C0.9800
C1—O1—C8116.1 (2)C2—C7—H7119.3
C10—N1—C12105.4 (2)C6—C7—H7119.3
C10—N1—C9125.2 (2)O1—C8—C9107.0 (2)
C12—N1—C9129.4 (2)O1—C8—H8A110.3
C10—N2—C11106.0 (2)C9—C8—H8A110.3
O3—N3—O4122.8 (3)O1—C8—H8B110.3
O3—N3—C3119.2 (2)C9—C8—H8B110.3
O4—N3—C3118.0 (3)H8A—C8—H8B108.6
O5—N4—O6123.5 (2)N1—C9—C8112.0 (2)
O5—N4—C12119.6 (2)N1—C9—H9A109.2
O6—N4—C12116.9 (2)C8—C9—H9A109.2
O2—C1—O1124.7 (3)N1—C9—H9B109.2
O2—C1—C2123.6 (3)C8—C9—H9B109.2
O1—C1—C2111.6 (2)H9A—C9—H9B107.9
C7—C2—C3116.2 (3)N2—C10—N1111.7 (2)
C7—C2—C1119.0 (3)N2—C10—C13123.8 (2)
C3—C2—C1124.8 (3)N1—C10—C13124.4 (2)
C4—C3—C2123.2 (3)N2—C11—C12109.3 (2)
C4—C3—N3117.5 (3)N2—C11—H11125.3
C2—C3—N3119.3 (2)C12—C11—H11125.3
C3—C4—C5119.2 (3)C11—C12—N1107.5 (2)
C3—C4—H4120.4C11—C12—N4127.2 (2)
C5—C4—H4120.4N1—C12—N4125.2 (2)
C4—C5—C6119.7 (3)C10—C13—H13A109.5
C4—C5—H5120.1C10—C13—H13B109.5
C6—C5—H5120.1H13A—C13—H13B109.5
C5—C6—C7120.4 (3)C10—C13—H13C109.5
C5—C6—H6119.8H13A—C13—H13C109.5
C7—C6—H6119.8H13B—C13—H13C109.5
C2—C7—C6121.3 (3)
C8—O1—C1—O2−8.7 (4)C1—O1—C8—C9172.1 (2)
C8—O1—C1—C2175.0 (2)C10—N1—C9—C899.1 (3)
O2—C1—C2—C7−72.3 (4)C12—N1—C9—C8−79.0 (3)
O1—C1—C2—C7104.2 (3)O1—C8—C9—N1−70.4 (3)
O2—C1—C2—C3107.2 (3)C11—N2—C10—N10.9 (3)
O1—C1—C2—C3−76.4 (3)C11—N2—C10—C13−177.9 (3)
C7—C2—C3—C40.5 (4)C12—N1—C10—N2−0.4 (3)
C1—C2—C3—C4−178.9 (3)C9—N1—C10—N2−178.9 (2)
C7—C2—C3—N3177.7 (2)C12—N1—C10—C13178.3 (3)
C1—C2—C3—N3−1.7 (4)C9—N1—C10—C13−0.2 (4)
O3—N3—C3—C4171.1 (3)C10—N2—C11—C12−1.0 (3)
O4—N3—C3—C4−8.4 (4)N2—C11—C12—N10.7 (3)
O3—N3—C3—C2−6.3 (4)N2—C11—C12—N4178.9 (3)
O4—N3—C3—C2174.2 (3)C10—N1—C12—C11−0.2 (3)
C2—C3—C4—C50.3 (4)C9—N1—C12—C11178.2 (2)
N3—C3—C4—C5−177.0 (2)C10—N1—C12—N4−178.4 (2)
C3—C4—C5—C6−0.2 (4)C9—N1—C12—N40.0 (4)
C4—C5—C6—C7−0.5 (4)O5—N4—C12—C11−179.6 (3)
C3—C2—C7—C6−1.3 (4)O6—N4—C12—C110.8 (4)
C1—C2—C7—C6178.2 (3)O5—N4—C12—N1−1.7 (4)
C5—C6—C7—C21.4 (4)O6—N4—C12—N1178.8 (3)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C11—H11···O5i0.952.583.474 (4)157
C9—H9B···O6ii0.992.453.166 (3)129
C9—H9B···O50.992.392.838 (3)107
C9—H9A···N2iii0.992.573.513 (4)159
C7—H7···O3iv0.952.433.190 (4)137

Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) x, −y+1/2, z+1/2; (iii) x, −y+3/2, z+1/2; (iv) x, −y+3/2, z−1/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: TK2618).

References

  • Bahadur, S., Anis, I., Shah, M. R. & Singh, K. (2009). Acta Cryst. E65, o1176. [PMC free article] [PubMed]
  • Bowden, K. & Izadi, J. (1997). Eur. J. Med. Chem.32, 995–1000.
  • Bruker (2001). SMART andSAINT Bruker AXS Inc., Madison, Wisconsin, USA.
  • Cosar, C., Crisan, C., Horclois, R., Jacob, R. M., Robert, J., Tchetitcheff, S. & Vaupr, R. (1966). Arzneim. Forsch16, 23–29. [PubMed]
  • Mao, W.-J., Lv, P.-C., Shi, L., Li, H.-Q. & Zhu, H.-L. (2009). Bioorg. Med. Chem.17, 7531–7536. [PubMed]
  • Sheldrick, G. M. (1997). SADABS University of Göttingen, Germany.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography