Ethyl 2-(2-methyl-4-nitro-1H-imidazol-1-yl)acetate

Wang, H.-Y.; Zou, P.; Xie, M.-H.; He, Y.-J.; Wu, J.

doi:10.1107/S1600536810037098

organic compounds

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ISSN: 2056-9890

Volume 66| Part 10| October 2010| Page o2606

doi:10.1107/S1600536810037098

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Ethyl 2-(2-methyl-4-nitro-1H-imidazol-1-yl)acetate

Hong-Yong Wang,^a Pei Zou,^a ^* Min-Hao Xie,^a Yong-Jun He ^a and Jun Wu ^a

^aKey Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, People's Republic of China
^*Correspondence e-mail: wywhy007@yahoo.com.cn

(Received 8 September 2010; accepted 16 September 2010; online 25 September 2010)

In the title compound, C₈H₁₁N₃O₄, the dihedral angle between the imidazole ring and the ethyl acetate plane is 103.1 (8)°. The crystal packing is stabilized by weak intermolecular C—H⋯O and C—H⋯N hydrogen bonds.

Related literature

For the possible use of nitroimidazole derivatives as radio sensitizers, to enhance the lethal effect of ionizing radiation on hypoxic tissues, see: Brown (1989 ); Chapman (1979 ); Chu et al. (2004 ).

Experimental

Crystal data

C₈H₁₁N₃O₄
M_r = 213.20
Orthorhombic, P 2₁ 2₁ 2₁
a = 4.416 (3) Å
b = 10.290 (6) Å
c = 20.769 (12) Å
V = 943.7 (10) Å³
Z = 4
Mo Kα radiation
μ = 0.12 mm⁻¹
T = 103 K
0.53 × 0.53 × 0.18 mm

Data collection

Rigaku SPIDER diffractometer
7883 measured reflections
1306 independent reflections
1161 reflections with I > 2σ(I)
R_int = 0.037

Refinement

R[F² > 2σ(F²)] = 0.033
wR(F²) = 0.082
S = 1.00
1306 reflections
138 parameters
H-atom parameters constrained
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C5—H5A⋯O4ⁱ	0.99	2.56	3.338 (3)	135
C5—H5A⋯N2ⁱ	0.99	2.56	3.509 (3)	160
C5—H5B⋯O2ⁱⁱ	0.99	2.39	3.175 (3)	136
C7—H7A⋯O2ⁱⁱⁱ	0.99	2.46	3.362 (3)	151
Symmetry codes: (i) $[-x+1, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (ii) x-1, y, z; (iii) $[x-{\script{1\over 2}}, -y+{\script{3\over 2}}, -z+1]$ .

Data collection: RAPID-AUTO (Rigaku, 2004 ); cell refinement: RAPID-AUTO; data reduction: RAPID-AUTO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810037098/pv2327sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536810037098/pv2327Isup2.hkl

checkCIF report

Comment top

Nitroimidazole derivatives have a tendency to be accumulated in the hypoxic regions leading to the possibility of envisaging these compounds as radio sensitizers, the agents which enhance the lethal effect of ionizing radiations on hypoxic tissues (Chapman, 1979; Brown, 1989; Chu et al., 2004). As a contribution to this field, we present here the title compound, (I), synthesized by a simple and efficient method.

In (I) (Fig. 1), the imidazole group is essentially planar and forms a dihedral angle of 103.1 (8)° with the ethyl acetate plane defined by atoms C5–C8/O1/O2. The nitro group lies in the plane of the imidazole group. In the cystal structure, the packing is stabilized by weak C—H···O and C—H···N interactions.

Related literature top

For the possible use of nitroimidazole derivatives as radio sensitizers, agents which enhance the lethal effect of ionizing radiation on hypoxic tissues, see: Brown (1989); Chapman (1979); Chu et al. (2004).

Experimental top

The title compound was prepared by the following procedure. To a solution of 2-methyl-4-nitroimidazole (2.11 g, 0.01 mol) in ethyl 2-chloroacetate (14.2 ml, 0.1 mol), propionic acid (6.66 ml) was added and refluxed for 16 h. The mixture was filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, ehtyl acetate/petroleum ether, 1:1). Single crystals were obtained by using ethanol/water (2:1) as solvents for recrystallization (m.p. 383–385 K).

Computing details top

Data collection: RAPID-AUTO (Rigaku, 2004); cell refinement: RAPID-AUTO (Rigaku, 2004); data reduction: RAPID-AUTO (Rigaku, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

Fig. 1. The molecular structure of the title compound, with the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.

Ethyl 2-(2-methyl-4-nitro-1H-imidazol-1-yl)acetate top

Crystal data top

C₈H₁₁N₃O₄	F(000) = 448
M_r = 213.20	D_x = 1.501 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 2529 reflections
a = 4.416 (3) Å	θ = 3.6–27.6°
b = 10.290 (6) Å	µ = 0.12 mm⁻¹
c = 20.769 (12) Å	T = 103 K
V = 943.7 (10) Å³	Chunk, colorless
Z = 4	0.53 × 0.53 × 0.18 mm

Data collection top

Rigaku SPIDER diffractometer	1161 reflections with I > 2σ(I)
Radiation source: Rotating Anode	R_int = 0.037
Graphite monochromator	θ_max = 27.6°, θ_min = 3.6°
ω scans	h = −5→5
7883 measured reflections	k = −13→13
1306 independent reflections	l = −27→27

Refinement top

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)] = 0.033	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.082	H-atom parameters constrained
S = 1.00	w = 1/[σ²(F_o²) + (0.0463P)² + 0.16P] where P = (F_o² + 2F_c²)/3
1306 reflections	(Δ/σ)_max < 0.001
138 parameters	Δρ_max = 0.24 e Å⁻³
0 restraints	Δρ_min = −0.20 e Å⁻³

Crystal data top

C₈H₁₁N₃O₄	V = 943.7 (10) Å³
M_r = 213.20	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 4.416 (3) Å	µ = 0.12 mm⁻¹
b = 10.290 (6) Å	T = 103 K
c = 20.769 (12) Å	0.53 × 0.53 × 0.18 mm

Data collection top

Rigaku SPIDER diffractometer	1161 reflections with I > 2σ(I)
7883 measured reflections	R_int = 0.037
1306 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.033	0 restraints
wR(F²) = 0.082	H-atom parameters constrained
S = 1.00	Δρ_max = 0.24 e Å⁻³
1306 reflections	Δρ_min = −0.20 e Å⁻³
138 parameters

Special details top

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.

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

	x	y	z	U_iso*/U_eq
O1	0.3643 (3)	0.58804 (13)	0.42377 (6)	0.0166 (3)
O2	0.7058 (4)	0.74979 (13)	0.42394 (6)	0.0192 (3)
O3	1.0605 (4)	0.80751 (14)	0.14662 (6)	0.0249 (4)
O4	1.1820 (4)	1.00386 (14)	0.17463 (7)	0.0232 (4)
N1	0.5079 (4)	0.82884 (15)	0.30422 (7)	0.0138 (3)
N2	0.7748 (4)	1.00021 (15)	0.27284 (7)	0.0153 (4)
N3	1.0373 (4)	0.90341 (16)	0.18170 (7)	0.0177 (4)
C1	0.6719 (5)	0.78850 (18)	0.25230 (8)	0.0158 (4)
H1	0.6754	0.7046	0.2332	0.019*
C2	0.8285 (5)	0.89536 (18)	0.23422 (8)	0.0146 (4)
C3	0.5780 (5)	0.95693 (18)	0.31538 (9)	0.0154 (4)
C4	0.4430 (5)	1.03335 (19)	0.36860 (9)	0.0188 (4)
H4A	0.5425	1.1183	0.3711	0.023*
H4B	0.4712	0.9868	0.4093	0.023*
H4C	0.2262	1.0455	0.3606	0.023*
C5	0.3162 (5)	0.74537 (19)	0.34314 (8)	0.0163 (4)
H5A	0.2462	0.6708	0.3170	0.020*
H5B	0.1357	0.7945	0.3576	0.020*
C6	0.4893 (5)	0.69604 (18)	0.40139 (8)	0.0155 (4)
C7	0.5214 (5)	0.52893 (19)	0.47784 (9)	0.0200 (4)
H7A	0.4783	0.5775	0.5180	0.024*
H7B	0.7428	0.5295	0.4704	0.024*
C8	0.4071 (6)	0.39131 (19)	0.48318 (10)	0.0237 (5)
H8A	0.1868	0.3921	0.4889	0.028*
H8B	0.5021	0.3489	0.5203	0.028*
H8C	0.4582	0.3435	0.4438	0.028*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0165 (8)	0.0124 (6)	0.0210 (6)	−0.0005 (6)	0.0002 (6)	0.0040 (5)
O2	0.0182 (8)	0.0166 (7)	0.0228 (7)	−0.0028 (7)	−0.0031 (6)	−0.0004 (5)
O3	0.0315 (9)	0.0198 (7)	0.0233 (7)	0.0025 (8)	0.0062 (6)	−0.0028 (6)
O4	0.0218 (9)	0.0181 (7)	0.0298 (7)	−0.0029 (8)	0.0051 (6)	0.0062 (6)
N1	0.0141 (9)	0.0111 (7)	0.0161 (7)	−0.0023 (7)	−0.0004 (6)	0.0009 (6)
N2	0.0175 (9)	0.0113 (7)	0.0171 (7)	−0.0002 (7)	−0.0004 (6)	0.0006 (6)
N3	0.0188 (10)	0.0151 (8)	0.0191 (7)	0.0027 (8)	0.0007 (7)	0.0041 (6)
C1	0.0193 (11)	0.0118 (9)	0.0164 (8)	−0.0006 (9)	−0.0007 (8)	−0.0003 (7)
C2	0.0159 (10)	0.0128 (9)	0.0151 (8)	0.0010 (9)	−0.0004 (7)	0.0012 (7)
C3	0.0177 (11)	0.0093 (8)	0.0193 (8)	−0.0015 (8)	−0.0029 (8)	0.0004 (7)
C4	0.0225 (12)	0.0147 (9)	0.0193 (8)	0.0001 (9)	0.0018 (8)	−0.0004 (7)
C5	0.0144 (10)	0.0137 (9)	0.0207 (9)	−0.0033 (9)	0.0008 (7)	0.0029 (7)
C6	0.0163 (10)	0.0117 (8)	0.0184 (8)	0.0016 (9)	0.0042 (8)	−0.0009 (7)
C7	0.0219 (12)	0.0187 (10)	0.0193 (9)	0.0028 (9)	−0.0005 (8)	0.0058 (7)
C8	0.0308 (13)	0.0164 (10)	0.0239 (10)	0.0040 (10)	0.0011 (9)	0.0039 (8)

Geometric parameters (Å, º) top

O1—C6	1.325 (2)	C3—C4	1.482 (3)
O1—C7	1.453 (2)	C4—H4A	0.9800
O2—C6	1.199 (2)	C4—H4B	0.9800
O3—N3	1.231 (2)	C4—H4C	0.9800
O4—N3	1.224 (2)	C5—C6	1.518 (3)
N1—C1	1.364 (2)	C5—H5A	0.9900
N1—C3	1.374 (2)	C5—H5B	0.9900
N1—C5	1.452 (2)	C7—C8	1.507 (3)
N2—C3	1.317 (3)	C7—H7A	0.9900
N2—C2	1.365 (2)	C7—H7B	0.9900
N3—C2	1.431 (2)	C8—H8A	0.9800
C1—C2	1.352 (3)	C8—H8B	0.9800
C1—H1	0.9500	C8—H8C	0.9800

C6—O1—C7	115.04 (16)	H4B—C4—H4C	109.5
C1—N1—C3	107.79 (17)	N1—C5—C6	110.35 (17)
C1—N1—C5	124.75 (16)	N1—C5—H5A	109.6
C3—N1—C5	127.24 (17)	C6—C5—H5A	109.6
C3—N2—C2	103.97 (16)	N1—C5—H5B	109.6
O4—N3—O3	124.24 (17)	C6—C5—H5B	109.6
O4—N3—C2	118.48 (16)	H5A—C5—H5B	108.1
O3—N3—C2	117.28 (17)	O2—C6—O1	125.57 (18)
C2—C1—N1	104.11 (16)	O2—C6—C5	123.93 (18)
C2—C1—H1	127.9	O1—C6—C5	110.49 (17)
N1—C1—H1	127.9	O1—C7—C8	106.88 (17)
C1—C2—N2	112.99 (17)	O1—C7—H7A	110.3
C1—C2—N3	126.05 (17)	C8—C7—H7A	110.3
N2—C2—N3	120.94 (17)	O1—C7—H7B	110.3
N2—C3—N1	111.11 (17)	C8—C7—H7B	110.3
N2—C3—C4	125.90 (17)	H7A—C7—H7B	108.6
N1—C3—C4	122.98 (18)	C7—C8—H8A	109.5
C3—C4—H4A	109.5	C7—C8—H8B	109.5
C3—C4—H4B	109.5	H8A—C8—H8B	109.5
H4A—C4—H4B	109.5	C7—C8—H8C	109.5
C3—C4—H4C	109.5	H8A—C8—H8C	109.5
H4A—C4—H4C	109.5	H8B—C8—H8C	109.5

C3—N1—C1—C2	−1.0 (2)	C1—N1—C3—N2	0.8 (2)
C5—N1—C1—C2	−176.05 (18)	C5—N1—C3—N2	175.61 (18)
N1—C1—C2—N2	1.0 (2)	C1—N1—C3—C4	−179.65 (18)
N1—C1—C2—N3	179.56 (18)	C5—N1—C3—C4	−4.8 (3)
C3—N2—C2—C1	−0.6 (2)	C1—N1—C5—C6	94.6 (2)
C3—N2—C2—N3	−179.20 (17)	C3—N1—C5—C6	−79.4 (2)
O4—N3—C2—C1	−173.7 (2)	C7—O1—C6—O2	−3.9 (3)
O3—N3—C2—C1	5.9 (3)	C7—O1—C6—C5	177.17 (16)
O4—N3—C2—N2	4.7 (3)	N1—C5—C6—O2	23.4 (3)
O3—N3—C2—N2	−175.69 (18)	N1—C5—C6—O1	−157.72 (16)
C2—N2—C3—N1	−0.1 (2)	C6—O1—C7—C8	−163.26 (16)
C2—N2—C3—C4	−179.70 (19)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5A···O4ⁱ	0.99	2.56	3.338 (3)	135
C5—H5A···N2ⁱ	0.99	2.56	3.509 (3)	160
C5—H5B···O2ⁱⁱ	0.99	2.39	3.175 (3)	136
C7—H7A···O2ⁱⁱⁱ	0.99	2.46	3.362 (3)	151

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

Experimental details

Crystal data
Chemical formula	C₈H₁₁N₃O₄
M_r	213.20
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	103
a, b, c (Å)	4.416 (3), 10.290 (6), 20.769 (12)
V (Å³)	943.7 (10)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.12
Crystal size (mm)	0.53 × 0.53 × 0.18

Data collection
Diffractometer	Rigaku SPIDER diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	7883, 1306, 1161
R_int	0.037
(sin θ/λ)_max (Å⁻¹)	0.651

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.033, 0.082, 1.00
No. of reflections	1306
No. of parameters	138
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.24, −0.20

Computer programs: RAPID-AUTO (Rigaku, 2004), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5A···O4ⁱ	0.99	2.56	3.338 (3)	135.4
C5—H5A···N2ⁱ	0.99	2.56	3.509 (3)	160.4
C5—H5B···O2ⁱⁱ	0.99	2.39	3.175 (3)	135.6
C7—H7A···O2ⁱⁱⁱ	0.99	2.46	3.362 (3)	150.5

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

Acknowledgements

The authors acknowledge financial support from Jiangsu Institute of Nuclear Medicine.

References

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