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Acta Crystallogr Sect E Struct Rep Online. 2008 September 1; 64(Pt 9): o1690.
Published online 2008 August 6. doi:  10.1107/S1600536808023726
PMCID: PMC2960585

1,2-Bis[2-(2-nitro-1H-imidazol-1-yl)eth­oxy]ethane

Abstract

In the crystal structure, the title compound, C12H16N6O6, lies on an inversion centre. The mol­ecule has an anti­periplanar conformation with respect to the C—C bond of the central ethane unit and the two imidazole rings are parallel to each other. The dihedral angle between the imidazole ring and the mean plane of the C and O atoms of the bis­(eth­oxy)ethane group is 76.04 (6)°. The mol­ecules are stacked along the c axis through a weak C—H(...)O inter­action and a π(...)π inter­action between the imidazole rings with a centroid–centroid distance of 3.5162 (6) Å. An intramolecular C—H(...)O hydrogen bond is also present.

Related literature

For bond-length data, see: Allen et al. (1987 [triangle]). For the applications of nitro­imidazoles, see, for example: Abdel-Jalil et al. (2006 [triangle]); Kennedy et al. (2006 [triangle]); Nagasawa et al. (2006 [triangle]); Nunn et al. (1995 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-64-o1690-scheme1.jpg

Experimental

Crystal data

  • C12H16N6O6
  • M r = 340.31
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-o1690-efi1.jpg
  • a = 7.0534 (1) Å
  • b = 15.5792 (2) Å
  • c = 6.8069 (1) Å
  • β = 99.560 (1)°
  • V = 737.60 (2) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.13 mm−1
  • T = 100.0 (1) K
  • 0.40 × 0.30 × 0.15 mm

Data collection

  • Bruker SMART APEXII CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2005 [triangle]) T min = 0.952, T max = 0.982
  • 11084 measured reflections
  • 2140 independent reflections
  • 1864 reflections with I > 2σ(I)
  • R int = 0.024

Refinement

  • R[F 2 > 2σ(F 2)] = 0.037
  • wR(F 2) = 0.106
  • S = 1.05
  • 2140 reflections
  • 141 parameters
  • All H-atom parameters refined
  • Δρmax = 0.49 e Å−3
  • Δρmin = −0.32 e Å−3

Data collection: APEX2 (Bruker, 2005 [triangle]); cell refinement: APEX2; data reduction: SAINT (Bruker, 2005 [triangle]); program(s) used to solve structure: SHELXTL (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2003 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808023726/is2317sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808023726/is2317Isup2.hkl

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

Acknowledgments

The authors gratefully acknowledge the financial assistance of Beijing Normal University. The authors also thank Universiti Sains Malaysia for the Research University Golden Goose (grant No. 1001/PFIZIK/811012).

supplementary crystallographic information

Comment

Depending on the availability of oxygen in tissue, nitroimidazoles can undergo different intracellular metabolism. In a normal cell, the molecule undergoes reduction to become a potentially reactive species and can be reoxidized in the presence of normal oxygen levels. In hypoxic tissue, however, the low oxygen concentration is not able to effectively reoxidize the molecule which results in more reactive intermediates that bind with components of hypoxic tissues (Nunn et al., 1995). Thus these compounds can function as hypoxia markers for imaging of hypoxic cells and have received much attention in medicinal and clinic studies (Abdel-Jalil et al., 2006; Kennedy et al., 2006; Nagasawa et al., 2006). In an attempt to develop new hypoxic cell radiosensitizers, we present herein the synthesis and crystal structure of the title nitorimidazole compound, (I).

The molecule of the title compound, C12H16N6O6, lies on an crystallographic inversion centre, so the asymmetric unit contains half of the molecule. The molecular structure has an antiperiplanar conformation with the two imidazole rings parallel to each other. The imidazole ring is planar, within a deviation of ±0.003 Å. The nitro group is twisted from the mean plane of imidazole ring with torsion angles O1–N3–C1–N1 = -6.49 (16)° and O2–N3–C1–N1 = 173.61 (9)°. Atoms C5, O3, C6, C5i, O3i and C6i [symmetry code: (i) 1 - x, 1 - y, -z] lie on the same plane. The interplanar angle between the C5/O3/C6/C5i/O3i/C6i plane and the imidazole ring (N1/N2/C1–C3) is 76.04 (6)°. The conformation of the ethoxyethane group is (-)-syn-clinal with respect to the imidazole ring, which is reflected by the torsion angle N2–C4–C5–O3 = -72.25 (9)°. Bond distances and angles have normal values (Allen et al., 1987).

The crystal packing of (I) in Fig. 2 shows that the molecules are linked by weak C—H···O interactions (Table 1) and stacked into columns along the c axis. The molecules in the adjacent columns are in a face-to-face fashion (Fig. 3). The crystal is stabilized by a weak C—H···O interaction (Table 1). A π···π interaction was also observed in the crystal with the Cg1···Cg1ii [symmetry code: (ii) x, 1/2 - y, -1/2 + z] distance of 3.5162 (6) Å; Cg1 is the centroid of the N1/N2/C1–C3 ring.

Experimental

To a solution of the triethyleneglycol ditosylate (0.458 g, 1.0 mmol) and triethyamine (244 mg, 2.4 mmol) in DMF (10 ml) was added a solution of 2-nitroimidazole (249 mg, 2.2 mmol) in DMF (10 ml) under argon. The mixture was stirred at 313 K for 4 days. After concentration on the rotary unit under reduced pressure, ethyl acetate (80 ml) was then added to the reaction residue, washed with water (20 ml × 3), dried (Na2SO4) and the organic layer was evaporated to dryness and subjected to chromatography on silica with 50% EtOAc-hexane to afford the desired compound (I) (0.255 g, yield 75%). Analysis calcd for C12H16N6O6: C 42.35, H 4.74, N 24.70%; found: C 42.01, H 4.71, N 24.43%. Single crystals suitable for X-ray diffraction analysis were obtained by the slow diffusion of hexane into the dichloromethane solution of the title compound.

Refinement

All H atoms were located in a difference map and refined isotropically.

Figures

Fig. 1.
The molecular structure of (I), showing 50% probability displacement ellipsoids and the atomic numbering.
Fig. 2.
The crystal packing of (I), viewed down the c axis, showing stacking of molecules along the c axis. Hydrogen bonds are shown as dashed lines.
Fig. 3.
The crystal packing of (I), viewed down the a axis. Hydrogen bonds are shown as dashed lines.

Crystal data

C12H16N6O6F000 = 356
Mr = 340.31Dx = 1.532 Mg m3
Monoclinic, P21/cMo Kα radiation λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 2140 reflections
a = 7.0534 (1) Åθ = 2.6–30.0º
b = 15.5792 (2) ŵ = 0.13 mm1
c = 6.8069 (1) ÅT = 100.0 (1) K
β = 99.560 (1)ºBlock, colorless
V = 737.597 (18) Å30.40 × 0.30 × 0.15 mm
Z = 2

Data collection

Bruker SMART APEXII CCD area-detector diffractometer2140 independent reflections
Radiation source: fine-focus sealed tube1864 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.024
Detector resolution: 8.33 pixels mm-1θmax = 30.0º
T = 100.0(1) Kθmin = 2.6º
ω scansh = −9→9
Absorption correction: multi-scan(SADABS; Bruker, 2005)k = −19→21
Tmin = 0.952, Tmax = 0.982l = −9→9
11084 measured reflections

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.037All H-atom parameters refined
wR(F2) = 0.106  w = 1/[σ2(Fo2) + (0.0604P)2 + 0.1626P] where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max = 0.001
2140 reflectionsΔρmax = 0.50 e Å3
141 parametersΔρmin = −0.32 e Å3
Primary atom site location: structure-invariant direct methodsExtinction correction: none

Special details

Experimental. The low-temparture data was collected with the Oxford Cryosystem Cobra low-temperature attachment.
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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 > σ(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. The highest residual electron density peak is located at 0.76 Å from C6 and the deepest hole is located at 1.04 Å from C1.

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

xyzUiso*/Ueq
O1−0.11911 (13)0.21335 (6)0.31449 (16)0.0405 (2)
O2−0.12171 (11)0.35244 (5)0.34055 (13)0.0319 (2)
O30.39505 (9)0.47777 (4)0.21737 (9)0.01816 (16)
N10.25143 (13)0.20738 (5)0.49696 (13)0.02131 (19)
N20.26946 (11)0.35116 (5)0.49565 (11)0.01551 (17)
N3−0.04022 (13)0.28202 (6)0.36307 (14)0.0243 (2)
C10.15885 (13)0.27986 (6)0.45100 (14)0.0183 (2)
C20.43305 (14)0.23267 (6)0.57559 (14)0.0209 (2)
C30.44699 (13)0.32065 (6)0.57493 (13)0.01808 (19)
C40.22148 (14)0.44265 (6)0.47476 (13)0.01791 (19)
C50.20547 (13)0.47446 (6)0.26222 (13)0.01829 (19)
C60.39581 (14)0.49935 (6)0.01416 (13)0.0190 (2)
H20.535 (2)0.1921 (9)0.625 (2)0.024 (3)*
H30.5512 (19)0.3594 (8)0.6195 (19)0.020 (3)*
H4A0.3268 (19)0.4727 (8)0.5584 (19)0.020 (3)*
H4B0.1055 (19)0.4504 (8)0.5245 (19)0.022 (3)*
H5A0.1496 (18)0.5319 (8)0.2511 (18)0.020 (3)*
H5B0.1250 (17)0.4375 (8)0.1698 (18)0.017 (3)*
H6A0.3216 (18)0.4569 (8)−0.0729 (19)0.021 (3)*
H6B0.3398 (17)0.5550 (8)−0.0139 (18)0.017 (3)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0272 (4)0.0366 (5)0.0539 (6)−0.0129 (3)−0.0041 (4)−0.0045 (4)
O20.0186 (4)0.0345 (4)0.0408 (5)0.0023 (3)−0.0004 (3)0.0128 (3)
O30.0189 (3)0.0223 (3)0.0136 (3)−0.0025 (2)0.0038 (2)0.0027 (2)
N10.0249 (4)0.0174 (4)0.0216 (4)0.0000 (3)0.0037 (3)0.0023 (3)
N20.0152 (3)0.0162 (4)0.0152 (3)0.0008 (3)0.0028 (3)0.0021 (2)
N30.0187 (4)0.0287 (5)0.0246 (4)−0.0047 (3)0.0009 (3)0.0043 (3)
C10.0166 (4)0.0198 (4)0.0183 (4)−0.0018 (3)0.0021 (3)0.0028 (3)
C20.0217 (5)0.0206 (4)0.0199 (4)0.0050 (3)0.0024 (3)0.0018 (3)
C30.0156 (4)0.0208 (4)0.0173 (4)0.0021 (3)0.0013 (3)0.0006 (3)
C40.0216 (4)0.0155 (4)0.0179 (4)0.0033 (3)0.0069 (3)0.0023 (3)
C50.0196 (4)0.0177 (4)0.0183 (4)0.0019 (3)0.0054 (3)0.0039 (3)
C60.0218 (5)0.0213 (4)0.0139 (4)−0.0030 (3)0.0035 (3)0.0035 (3)

Geometric parameters (Å, °)

O1—N31.2258 (12)C2—H20.977 (14)
O2—N31.2361 (12)C3—H30.961 (13)
O3—C51.4211 (11)C4—C51.5156 (12)
O3—C61.4243 (10)C4—H4A0.977 (13)
N1—C11.3160 (12)C4—H4B0.943 (13)
N1—C21.3620 (13)C5—H5A0.976 (12)
N2—C11.3623 (11)C5—H5B0.964 (12)
N2—C31.3641 (11)C6—C6i1.5140 (19)
N2—C41.4664 (11)C6—H6A0.980 (13)
N3—C11.4324 (13)C6—H6B0.958 (13)
C2—C31.3741 (14)
C5—O3—C6111.88 (7)N2—C4—H4A105.6 (7)
C1—N1—C2104.03 (8)C5—C4—H4A109.1 (7)
C1—N2—C3104.96 (8)N2—C4—H4B106.8 (8)
C1—N2—C4131.03 (8)C5—C4—H4B111.7 (8)
C3—N2—C4123.99 (8)H4A—C4—H4B110.5 (11)
O1—N3—O2124.07 (10)O3—C5—C4107.06 (7)
O1—N3—C1117.50 (9)O3—C5—H5A109.4 (7)
O2—N3—C1118.43 (8)C4—C5—H5A109.8 (7)
N1—C1—N2113.79 (8)O3—C5—H5B110.8 (7)
N1—C1—N3122.19 (8)C4—C5—H5B111.7 (7)
N2—C1—N3124.01 (8)H5A—C5—H5B108.1 (11)
N1—C2—C3110.51 (8)O3—C6—C6i106.69 (9)
N1—C2—H2122.7 (8)O3—C6—H6A109.9 (7)
C3—C2—H2126.7 (8)C6i—C6—H6A111.4 (7)
N2—C3—C2106.70 (8)O3—C6—H6B109.8 (7)
N2—C3—H3120.7 (8)C6i—C6—H6B109.8 (7)
C2—C3—H3132.6 (8)H6A—C6—H6B109.2 (11)
N2—C4—C5112.94 (7)
C2—N1—C1—N2−0.18 (11)C1—N1—C2—C3−0.23 (11)
C2—N1—C1—N3−179.90 (9)C1—N2—C3—C2−0.61 (10)
C3—N2—C1—N10.51 (11)C4—N2—C3—C2177.86 (8)
C4—N2—C1—N1−177.81 (8)N1—C2—C3—N20.54 (10)
C3—N2—C1—N3−179.78 (9)C1—N2—C4—C5−77.42 (12)
C4—N2—C1—N31.90 (15)C3—N2—C4—C5104.54 (10)
O1—N3—C1—N1−6.49 (16)C6—O3—C5—C4174.54 (7)
O2—N3—C1—N1173.61 (9)N2—C4—C5—O3−72.25 (9)
O1—N3—C1—N2173.82 (9)C5—O3—C6—C6i−179.94 (9)
O2—N3—C1—N2−6.08 (15)

Symmetry codes: (i) −x+1, −y+1, −z.

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C4—H4A···O3ii0.977 (13)2.404 (13)3.3707 (11)170.1 (10)
C4—H4B···O20.944 (14)2.408 (13)2.8169 (13)105.9 (9)

Symmetry codes: (ii) −x+1, −y+1, −z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: IS2317).

References

  • Abdel-Jalil, R. J., Uebele, M., Ehrlichmann, W., Voelter, W. & Machulla, H. J. (2006). J. Radioanal. Nucl. Chem.267, 557–560.
  • Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–S19.
  • Bruker (2005). APEX2, SAINT and SADABS Bruker AXS Inc., Madison, Wisconsin, USA.
  • Kennedy, D. C., Wu, A., Patrick, B. O. & James, B. R. (2006). J. Inorg. Biochem.100, 1974–1982. [PubMed]
  • Nagasawa, H., Uto, Y., Kirk, K. L. & Hori, H. (2006). Biol. Pharm. Bull.29, 2335–2342. [PubMed]
  • Nunn, A., Linder, K. & Strauss, W. H. (1995). Eur. J. Nucl. Med.22, 265–280. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2003). J. Appl. Cryst.36, 7–13.

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