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

Shu-Xian Li; Lin Zhu; Hua-Min Li; Hoong-Kun Fun; Suchada Chantrapromma

doi:10.1107/S1600536808023726

. 2008 Aug 6;64(Pt 9):o1690. doi: 10.1107/S1600536808023726

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

Shu-Xian Li ^a,^‡, Lin Zhu ^a, Hua-Min Li ^a,^§, Hoong-Kun Fun ^b,^*, Suchada Chantrapromma ^c,^¶

PMCID: PMC2960585 PMID: 21201679

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 ▶). For the applications of nitroimidazoles, see, for example: Abdel-Jalil et al. (2006 ▶); Kennedy et al. (2006 ▶); Nagasawa et al. (2006 ▶); Nunn et al. (1995 ▶).

Experimental

Crystal data

C₁₂H₁₆N₆O₆
M _r = 340.31
Monoclinic,
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 ▶) 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
Δρ_max = 0.49 e Å⁻³
Δρ_min = −0.32 e Å⁻³

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

Supplementary Material

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

e-64-o1690-sup1.cif^{(15.9KB, cif)}

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

e-64-o1690-Isup2.hkl^{(105.2KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C4—H4A⋯O3ⁱ	0.977 (13)	2.404 (13)	3.3707 (11)	170.1 (10)
C4—H4B⋯O2	0.944 (14)	2.408 (13)	2.8169 (13)	105.9 (9)

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Symmetry code: (i) Inline graphic .

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.