4-(2-{2-[2-(2-Nitro-1H-imidazol-1-yl)ethoxy]eth­oxy}eth­oxy)benzaldehyde

Shu-Xian Li; Da-Hai Zhang; Hoong-Kun Fun; Madhukar Hemamalini

doi:10.1107/S1600536811014322

. 2011 Apr 22;67(Pt 5):o1206. doi: 10.1107/S1600536811014322

4-(2-{2-[2-(2-Nitro-1H-imidazol-1-yl)ethoxy]ethoxy}ethoxy)benzaldehyde

Shu-Xian Li ^a,^‡, Da-Hai Zhang ^a, Hoong-Kun Fun ^b,^*,^§, Madhukar Hemamalini ^b

PMCID: PMC3089305 PMID: 21754505

Abstract

In the molecule of the title compound, C₁₆H₁₉N₃O₆, the imidazole ring is essentially planar [maximum deviation = 0.002 (2) Å] and forms a dihedral angle of 5.08 (14)° with the nitro group. In the crystal structure, adjacent molecules are connected via intermolecular C—H⋯O hydrogen bonds into columns parallel to the a axis.

Related literature

For details and applications of nitroimidazole, see: Abdel-Jalil et al. (2006 ▶); Kennedy et al. (2006 ▶); Nagasawa et al. (2006 ▶); Nunn et al. (1995 ▶). For bond-length data, see: Allen et al. (1987 ▶). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C₁₆H₁₉N₃O₆
M _r = 349.34
Orthorhombic,
a = 4.4403 (3) Å
b = 11.4686 (8) Å
c = 31.2763 (19) Å
V = 1592.72 (18) Å³
Z = 4
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 100 K
1.00 × 0.10 × 0.09 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.895, T _max = 0.990
11825 measured reflections
2763 independent reflections
2243 reflections with I > 2σ(I)
R _int = 0.045

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.094
S = 1.03
2763 reflections
226 parameters
H-atom parameters constrained
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; 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, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811014322/rz2583sup1.cif

e-67-o1206-sup1.cif^{(19.6KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811014322/rz2583Isup2.hkl

e-67-o1206-Isup2.hkl^{(132.9KB, 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
C9—H9B⋯O4ⁱ	0.97	2.56	3.335 (3)	137
C10—H10A⋯O4ⁱⁱ	0.97	2.57	3.461 (3)	152

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

SXL and DHZ gratefully acknowledge the financial assistance of Handan College. The authors thank the Malaysian Government and Universiti Sains Malaysia for Scientific Advancement Grant Allocation (SAGA) grant No. 304/PFIZIK/653003/A118. HKF and MH thank the Malaysian Government and Universiti Sains Malaysia for Research University grant No. 1001/PFIZIK/811160. MH also thanks Universiti Sains Malaysia for a postdoctoral research fellowship.

supplementary crystallographic information

Comment

Nitroimidazole is an important building block in the design and synthesis of hypoxia makers (Abdel-Jalil et al. 2006; Kennedy et al. 2006, Nagasawa et al., 2006). In a normal cell, the nitroimidazole moiety undergoes reduction to become a potentially reactive species and can be reoxidized in the presence of normal oxygen levels. However in hypoxic tissues, the low oxygen concentration is not able to effectively reoxidize the molecule and this results in more reactive intermediates that bind with the components of hypoxic tissues (Nunn et al., 1995). In an attempt to develop new hypoxic cell radiosensitizers, we present herein the crystal structure of 4-(2-(2-(2-(2-nitro-1H-imidazol-1-yl) ethoxy)-ethoxy)ethoxy)benzaldehyde (I).

In (I), (Fig. 1), the imidazole group is essentially planar, with a maximum deviation of 0.002 (2) Å for atom N2. The nitro group is twisted from the mean plane of imidazole ring with torsion angles O5—N3—C15—N1 = -3.7 (3)° and O6—N3—C15—N1 = 176.7 (2)°. The conformation of the 1-(2-(2-ethoxy)ethoxy)ethyl)propane group is (-)-syn-clinal with respect to the imidazole ring, which is reflected by the torsion angle N1—C12—C11—O3 = -105.5 (2)°. The dihedral angle between the imidazole (N1–N2/C13–C15) ring and the benzene (C1–C6) ring is 38.60 (13)°. Bond distances and angles have normal values (Allen et al., 1987).

The crystal packing (Fig. 2) shows that the molecules are linked by weak intermolecular C9—H9B···O4 and C10—H10A···O4 (Table 1) hydrogen interactions into columns parallel to the a axis.

Experimental

To a solution of the 4-(2-(2-(2-(2-nitro-1H-imidazol-1-yl)ethoxy) ethoxy)ethyl-4-methylbenzenesulfonate (0.600 g, 1.5 mmol) and potassium carbonate (0.569 g, 4.1 mmol) in DMF (20 mL) was added a solution of 4-hydroxybenzaldehyde (0.166 g, 1.4 mmol) in DMF (10 ml) under argon atmosphere. The mixture was stirred at 120°C for 20 h. After concentration on the rotary evaporator under reduced pressure, ethyl acetate (80 ml) was then added to the reaction residue. The content was then washed with water (20 ml × 3), dried (Na₂SO₄) and the organic layer was evaporated to dryness and subjected to chromatography on silica with EtOAc–hexane (3:1 v/v) to afford the desired compound (I) (0.435 g, yield 89%). Analysis Calcd for C₁₆H₁₉N₃O₆: C 55.01, H 5.48, N 12.03%; found: C 55.31, H 4.91, N 12.43%. ¹H NMR (500 MHz, CDCl₃) δ: 3.66 (m, 4H), 3.86 (m, 4H), 4.22 (t, J = 4.5 Hz, 2H), 4.64 (t, J = 4.5 Hz, 2H), 7.04 (d, J = 9.0, 2H), 7.10 (s, 1H), 7.23 (s, 1H), 7.87 (d, J = 9.0 Hz, 2H), 9.91 (s, 1H). Single crystals of X-ray diffraction quality were prepared by the slow diffusion of hexane into a dichloromethane solution of the title compound.