3-Meth­oxy-4-[3-(2-methyl-4-nitro-1H-imidazol-1-yl)prop­oxy]benzaldehyde

Jin, L.; Wang, G.-Z.; Zhou, C.-H.

doi:10.1107/S1600536809031894

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 65| Part 9| September 2009| Page o2164

doi:10.1107/S1600536809031894

Open

access

3-Methoxy-4-[3-(2-methyl-4-nitro-1H-imidazol-1-yl)propoxy]benzaldehyde

Lei Jin,^a,^b Guang-Zhou Wang ^a and Cheng-He Zhou ^a ^*

^aLaboratory of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, People's Republic of China, and ^bSchool of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China
^*Correspondence e-mail: zhouch@swu.edu.cn

(Received 2 August 2009; accepted 12 August 2009; online 15 August 2009)

In the title molecule, C₁₅H₁₇N₃O₅, the dihedral angle between the benzene and imidazole rings is 3.69 (2)°. The crystal structure is stabilized by weak intermolecular C—H⋯O hydrogen bonds and π–π stacking interactions with a centroid–centroid distance of 3.614 (1) Å.

Related literature

For general background to the biological activity of nitroimidazole and its derivatives, see:Demirayak et al. (1999 ); Huang et al. (2007 ); Olender et al. (2009 ). For the synthetic procedure, see: Khalafi-Nezhad et al. (2005 ).

Experimental

Crystal data

C₁₅H₁₇N₃O₅
M_r = 319.32
Monoclinic, P 2₁ /n
a = 9.4885 (14) Å
b = 13.048 (2) Å
c = 12.745 (2) Å
β = 101.120 (3)°
V = 1548.3 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 173 K
0.28 × 0.24 × 0.2 mm

Data collection

Bruker SMART CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ) T_min = 0.971, T_max = 0.979
7761 measured reflections
3329 independent reflections
2329 reflections with I > 2σ(I)
R_int = 0.022

Refinement

R[F² > 2σ(F²)] = 0.043
wR(F²) = 0.130
S = 1.03
3329 reflections
210 parameters
H-atom parameters constrained
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.19 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C4—H4B⋯O4ⁱ	0.98	2.58	3.415 (3)	144
C8—H8⋯O4ⁱⁱ	0.95	2.51	3.229 (2)	133
C10—H10B⋯O2ⁱⁱⁱ	0.99	2.56	3.312 (2)	133
C10—H10A⋯O1^iv	0.99	2.58	3.461 (2)	148
C14—H14⋯O1^iv	0.95	2.29	3.166 (2)	153
Symmetry codes: (i) $[x+{\script{1\over 2}}, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]$ ; (ii) x, y+1, z; (iii) -x, -y+1, -z; (iv) $[x-{\script{1\over 2}}, -y+{\script{3\over 2}}, z+{\script{1\over 2}}]$ .

Data collection: SMART (Bruker, 2000 ); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg & Putz, 1999 ); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809031894/lh2876sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809031894/lh2876Isup2.hkl

checkCIF report

Comment top

Nitroimidazole and its derivatives possess several biological activities such as radiosensitizer, anti-tuberculosis and antimicrobial (Demirayak et al., 1999; Huang et al., 2007; Olender et al., 2009). In view of the therapeutic potentials of nitroimidazole derivatives, we are interested in the research and development of nitroimidazole compounds as drugs. Herein we report the crystal structure of the title compound (I).

The stucture of the title compound (I) is shown in Fig 1. In the molecule the dihedral angle between the benzene and imidazole rings is 3.69 (2)°. The crystal structure is stabilized by weak intermolecular C—H···O hydrogen bonds and significant π–π stacking interactions with a centroid to centroid ditance of 3.614 (1)Å between benzene and imidazole rings related by the symmetry operator (1/2-x, 1/2+y, 1/2-z).

Related literature top

For general background to the biological activity of nitroimidazole and its derivatives, see:Demirayak et al. (1999); Huang et al. (2007); Olender et al. (2009). For the synthetic procedure, see: Khalafi-Nezhad et al. (2005).

Experimental top

Compound (I) was synthesized according to the procedure of Khalafi-Nezhad et al. (2005). Single crystals used in X-ray diffraction studies were grown by slow evaporation at room temperature of solutions of (I) in ethyl acetate and dichlormethane mixtures.

Computing details top

Data collection: SMART (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT (Bruker, 2000); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg & Putz, 1999); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

Fig. 1. The molecular structure of (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.

3-Methoxy-4-[3-(2-methyl-4-nitro-1H-imidazol-1-yl)propoxy]benzaldehyde top

Crystal data top

C₁₅H₁₇N₃O₅	F(000) = 672
M_r = 319.32	D_x = 1.370 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 3149 reflections
a = 9.4885 (14) Å	θ = 2.3–26.9°
b = 13.048 (2) Å	µ = 0.10 mm⁻¹
c = 12.745 (2) Å	T = 173 K
β = 101.120 (3)°	Block, colorless
V = 1548.3 (4) Å³	0.28 × 0.24 × 0.2 mm
Z = 4

Data collection top

Bruker SMART CCD diffractometer	3329 independent reflections
Radiation source: fine-focus sealed tube	2329 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.022
ϕ and ω scans	θ_max = 27.0°, θ_min = 2.3°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −7→12
T_min = 0.971, T_max = 0.979	k = −15→16
7761 measured reflections	l = −13→16

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)] = 0.043	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.130	H-atom parameters constrained
S = 1.03	w = 1/[σ²(F_o²) + (0.0623P)² + 0.3992P] where P = (F_o² + 2F_c²)/3
3329 reflections	(Δ/σ)_max < 0.001
210 parameters	Δρ_max = 0.27 e Å⁻³
0 restraints	Δρ_min = −0.19 e Å⁻³

Crystal data top

C₁₅H₁₇N₃O₅	V = 1548.3 (4) Å³
M_r = 319.32	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 9.4885 (14) Å	µ = 0.10 mm⁻¹
b = 13.048 (2) Å	T = 173 K
c = 12.745 (2) Å	0.28 × 0.24 × 0.2 mm
β = 101.120 (3)°

Data collection top

Bruker SMART CCD diffractometer	3329 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	2329 reflections with I > 2σ(I)
T_min = 0.971, T_max = 0.979	R_int = 0.022
7761 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.043	0 restraints
wR(F²) = 0.130	H-atom parameters constrained
S = 1.03	Δρ_max = 0.27 e Å⁻³
3329 reflections	Δρ_min = −0.19 e Å⁻³
210 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
C1	0.2645 (2)	1.03088 (14)	−0.03024 (16)	0.0502 (5)
H1	0.2344	1.0901	0.0028	0.060*
C2	0.21471 (17)	0.93177 (12)	0.00141 (13)	0.0363 (4)
C3	0.25719 (18)	0.84045 (12)	−0.04102 (14)	0.0381 (4)
H3	0.3193	0.8421	−0.0912	0.046*
C4	0.3482 (2)	0.65169 (17)	−0.1102 (2)	0.0691 (7)
H4A	0.3107	0.6882	−0.1769	0.104*
H4B	0.3681	0.5803	−0.1262	0.104*
H4C	0.4370	0.6847	−0.0737	0.104*
C5	0.20870 (17)	0.74857 (12)	−0.00975 (13)	0.0346 (4)
C6	0.11391 (16)	0.74686 (11)	0.06315 (12)	0.0305 (3)
C7	0.07388 (17)	0.83703 (11)	0.10519 (13)	0.0322 (4)
H7	0.0114	0.8359	0.1551	0.039*
C8	0.12529 (17)	0.92983 (12)	0.07433 (13)	0.0347 (4)
H8	0.0985	0.9921	0.1038	0.042*
C9	−0.01627 (18)	0.64126 (12)	0.16566 (14)	0.0360 (4)
H9A	−0.1090	0.6775	0.1440	0.043*
H9B	0.0344	0.6699	0.2346	0.043*
C10	−0.04042 (17)	0.52728 (12)	0.17563 (14)	0.0378 (4)
H10A	−0.1107	0.5152	0.2225	0.045*
H10B	−0.0800	0.4981	0.1043	0.045*
C11	0.0990 (2)	0.47573 (13)	0.2218 (2)	0.0616 (6)
H11A	0.1721	0.4966	0.1802	0.074*
H11B	0.1316	0.4999	0.2962	0.074*
C12	0.16148 (17)	0.29675 (13)	0.16772 (13)	0.0384 (4)
C13	0.2589 (2)	0.33135 (16)	0.09670 (16)	0.0560 (5)
H13A	0.2936	0.2717	0.0624	0.084*
H13B	0.3407	0.3680	0.1390	0.084*
H13C	0.2066	0.3772	0.0417	0.084*
C14	0.01304 (17)	0.30668 (12)	0.28026 (15)	0.0403 (4)
H14	−0.0475	0.3304	0.3264	0.048*
C15	0.04200 (16)	0.20834 (11)	0.25747 (13)	0.0326 (4)
N1	0.09014 (14)	0.36345 (10)	0.22222 (12)	0.0417 (4)
N2	0.13429 (14)	0.20076 (10)	0.18821 (11)	0.0346 (3)
N3	−0.01634 (15)	0.11998 (11)	0.29957 (12)	0.0404 (4)
O1	0.34061 (19)	1.04390 (12)	−0.09476 (13)	0.0758 (5)
O2	0.24432 (13)	0.65445 (9)	−0.04271 (11)	0.0493 (4)
O3	0.06945 (12)	0.65190 (8)	0.08547 (10)	0.0376 (3)
O4	0.02197 (15)	0.03485 (9)	0.27613 (12)	0.0544 (4)
O5	−0.10418 (15)	0.13411 (11)	0.35800 (12)	0.0611 (4)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0631 (12)	0.0379 (10)	0.0515 (11)	−0.0115 (8)	0.0156 (10)	0.0021 (8)
C2	0.0422 (9)	0.0306 (8)	0.0360 (9)	−0.0055 (7)	0.0074 (7)	0.0004 (7)
C3	0.0385 (9)	0.0378 (9)	0.0404 (9)	−0.0086 (7)	0.0139 (7)	−0.0058 (7)
C4	0.0556 (12)	0.0577 (13)	0.1071 (19)	−0.0074 (10)	0.0486 (13)	−0.0360 (13)
C5	0.0327 (8)	0.0294 (8)	0.0427 (9)	−0.0027 (6)	0.0097 (7)	−0.0106 (7)
C6	0.0306 (8)	0.0248 (7)	0.0355 (8)	−0.0027 (6)	0.0046 (6)	−0.0010 (6)
C7	0.0370 (8)	0.0285 (8)	0.0327 (8)	0.0011 (6)	0.0106 (7)	−0.0008 (6)
C8	0.0420 (9)	0.0249 (8)	0.0365 (9)	0.0012 (6)	0.0057 (7)	−0.0022 (6)
C9	0.0391 (9)	0.0279 (8)	0.0435 (9)	−0.0007 (7)	0.0140 (7)	0.0017 (7)
C10	0.0375 (9)	0.0284 (8)	0.0483 (10)	−0.0015 (7)	0.0106 (7)	0.0036 (7)
C11	0.0487 (11)	0.0249 (9)	0.0984 (17)	−0.0025 (8)	−0.0175 (11)	0.0050 (9)
C12	0.0367 (8)	0.0364 (9)	0.0391 (9)	−0.0067 (7)	−0.0004 (7)	0.0046 (7)
C13	0.0567 (12)	0.0595 (12)	0.0517 (12)	−0.0214 (10)	0.0102 (10)	0.0122 (10)
C14	0.0356 (8)	0.0316 (9)	0.0529 (11)	0.0045 (7)	0.0065 (8)	−0.0035 (8)
C15	0.0321 (8)	0.0273 (8)	0.0384 (9)	0.0018 (6)	0.0068 (7)	0.0007 (6)
N1	0.0360 (8)	0.0254 (7)	0.0597 (10)	−0.0008 (6)	−0.0008 (7)	0.0048 (6)
N2	0.0368 (7)	0.0309 (7)	0.0370 (7)	−0.0023 (6)	0.0092 (6)	0.0003 (6)
N3	0.0445 (8)	0.0319 (7)	0.0494 (9)	0.0022 (6)	0.0202 (7)	0.0034 (6)
O1	0.1041 (12)	0.0577 (9)	0.0781 (11)	−0.0285 (9)	0.0487 (10)	0.0027 (8)
O2	0.0480 (7)	0.0329 (7)	0.0749 (9)	−0.0048 (5)	0.0318 (7)	−0.0182 (6)
O3	0.0431 (6)	0.0236 (6)	0.0494 (7)	−0.0037 (5)	0.0176 (5)	−0.0026 (5)
O4	0.0732 (9)	0.0259 (6)	0.0739 (9)	0.0032 (6)	0.0383 (7)	0.0049 (6)
O5	0.0638 (9)	0.0543 (8)	0.0784 (10)	0.0023 (7)	0.0471 (8)	0.0018 (7)

Geometric parameters (Å, º) top

C1—O1	1.207 (2)	C9—H9B	0.9900
C1—C2	1.460 (2)	C10—C11	1.499 (2)
C1—H1	0.9500	C10—H10A	0.9900
C2—C8	1.374 (2)	C10—H10B	0.9900
C2—C3	1.400 (2)	C11—N1	1.468 (2)
C3—C5	1.371 (2)	C11—H11A	0.9900
C3—H3	0.9500	C11—H11B	0.9900
C4—O2	1.428 (2)	C12—N2	1.315 (2)
C4—H4A	0.9800	C12—N1	1.371 (2)
C4—H4B	0.9800	C12—C13	1.483 (2)
C4—H4C	0.9800	C13—H13A	0.9800
C5—O2	1.3615 (18)	C13—H13B	0.9800
C5—C6	1.412 (2)	C13—H13C	0.9800
C6—O3	1.3567 (18)	C14—C15	1.355 (2)
C6—C7	1.376 (2)	C14—N1	1.356 (2)
C7—C8	1.390 (2)	C14—H14	0.9500
C7—H7	0.9500	C15—N2	1.362 (2)
C8—H8	0.9500	C15—N3	1.428 (2)
C9—O3	1.4304 (19)	N3—O4	1.2235 (17)
C9—C10	1.514 (2)	N3—O5	1.2339 (18)
C9—H9A	0.9900

O1—C1—C2	125.53 (19)	C9—C10—H10A	109.7
O1—C1—H1	117.2	C11—C10—H10B	109.7
C2—C1—H1	117.2	C9—C10—H10B	109.7
C8—C2—C3	120.47 (14)	H10A—C10—H10B	108.2
C8—C2—C1	118.55 (15)	N1—C11—C10	113.74 (14)
C3—C2—C1	120.98 (16)	N1—C11—H11A	108.8
C5—C3—C2	119.63 (15)	C10—C11—H11A	108.8
C5—C3—H3	120.2	N1—C11—H11B	108.8
C2—C3—H3	120.2	C10—C11—H11B	108.8
O2—C4—H4A	109.5	H11A—C11—H11B	107.7
O2—C4—H4B	109.5	N2—C12—N1	111.65 (15)
H4A—C4—H4B	109.5	N2—C12—C13	125.48 (17)
O2—C4—H4C	109.5	N1—C12—C13	122.86 (16)
H4A—C4—H4C	109.5	C12—C13—H13A	109.5
H4B—C4—H4C	109.5	C12—C13—H13B	109.5
O2—C5—C3	125.59 (15)	H13A—C13—H13B	109.5
O2—C5—C6	114.59 (14)	C12—C13—H13C	109.5
C3—C5—C6	119.82 (14)	H13A—C13—H13C	109.5
O3—C6—C7	125.37 (14)	H13B—C13—H13C	109.5
O3—C6—C5	114.55 (13)	C15—C14—N1	104.31 (15)
C7—C6—C5	120.08 (14)	C15—C14—H14	127.8
C6—C7—C8	119.74 (14)	N1—C14—H14	127.8
C6—C7—H7	120.1	C14—C15—N2	112.96 (14)
C8—C7—H7	120.1	C14—C15—N3	125.07 (15)
C2—C8—C7	120.23 (14)	N2—C15—N3	121.97 (13)
C2—C8—H8	119.9	C14—N1—C12	107.49 (13)
C7—C8—H8	119.9	C14—N1—C11	125.74 (17)
O3—C9—C10	105.75 (12)	C12—N1—C11	126.73 (16)
O3—C9—H9A	110.6	C12—N2—C15	103.59 (13)
C10—C9—H9A	110.6	O4—N3—O5	123.37 (14)
O3—C9—H9B	110.6	O4—N3—C15	119.10 (13)
C10—C9—H9B	110.6	O5—N3—C15	117.52 (13)
H9A—C9—H9B	108.7	C5—O2—C4	116.73 (14)
C11—C10—C9	109.72 (14)	C6—O3—C9	118.76 (12)
C11—C10—H10A	109.7

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C4—H4B···O4ⁱ	0.98	2.58	3.415 (3)	144
C8—H8···O4ⁱⁱ	0.95	2.51	3.229 (2)	133
C10—H10B···O2ⁱⁱⁱ	0.99	2.56	3.312 (2)	133
C10—H10A···O1^iv	0.99	2.58	3.461 (2)	148
C14—H14···O1^iv	0.95	2.29	3.166 (2)	153

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

Experimental details

Crystal data
Chemical formula	C₁₅H₁₇N₃O₅
M_r	319.32
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	173
a, b, c (Å)	9.4885 (14), 13.048 (2), 12.745 (2)
β (°)	101.120 (3)
V (Å³)	1548.3 (4)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.28 × 0.24 × 0.2

Data collection
Diffractometer	Bruker SMART CCD diffractometer
Absorption correction	Multi-scan (SADABS; Sheldrick, 1996)
T_min, T_max	0.971, 0.979
No. of measured, independent and observed [I > 2σ(I)] reflections	7761, 3329, 2329
R_int	0.022
(sin θ/λ)_max (Å⁻¹)	0.640

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.043, 0.130, 1.03
No. of reflections	3329
No. of parameters	210
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.27, −0.19

Computer programs: SMART (Bruker, 2000), SAINT (Bruker, 2000), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), DIAMOND (Brandenburg & Putz, 1999), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C4—H4B···O4ⁱ	0.98	2.58	3.415 (3)	144
C8—H8···O4ⁱⁱ	0.95	2.51	3.229 (2)	133
C10—H10B···O2ⁱⁱⁱ	0.99	2.56	3.312 (2)	133
C10—H10A···O1^iv	0.99	2.58	3.461 (2)	148
C14—H14···O1^iv	0.95	2.29	3.166 (2)	153

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

Acknowledgements

We thank Southwest University (SWUB2006018, XSGX0602 and SWUF2007023) and the Natural Science Foundation of Chongqing (2007BB5369) for financial support.

References

Brandenburg, K. & Putz, H. (1999). DIADMOND. Crystal Impact GbR, Bonn, Germany. Google Scholar
Bruker (2000). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Demirayak, S., Karaburun, A. C. & Kiraz, N. (1999). Eur. J. Med. Chem. 34, 275–278. Web of Science CrossRef CAS Google Scholar
Huang, J. & Zhou, C. H. (2007). Chin. Clin. J. Tradit. Chin. West. Med. 7, 538–542. Google Scholar
Khalafi-Nezhad, A., Soltani Rad, M. N., Mohabatkar, H., Asrari, Z. & Hemmateenejad, B. (2005). Bioorg. Med. Chem. 13, 1931–1938. Web of Science CrossRef PubMed CAS Google Scholar
Olender, D., Zwawiak, J., Lukianchuk, V., Lesyk, R., Kropacz, A., Fojutowski, A. & Zaprutko, L. (2009). Eur. J. Med. Chem. 44, 645–652. Web of Science CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (1996). SADABS. University of Göttingen, Germany. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar