2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl 3-bromo­benzoate

Abstract

The mol­ecule of the title compound, C₁₃H₁₂BrN₃O₄, is non-planar, as indicated in the dihedral angle of 59.5 (4)° formed between the least-squares planes through the imidazole and benzene rings. In the crystal, mol­ecules are connected via C—H⋯O contacts, forming a supra­molecular chain.

Related literature

For potential pharmacological uses of benzoic acid derivatives, see: Correa-Basurto et al. (2005 ▶); Jetten et al. (1987 ▶); Kelly et al. (2007 ▶); Sato et al. (2005 ▶). For a related structure, see: Wang et al. (2008 ▶).

Experimental

Crystal data

• C₁₃H₁₂BrN₃O₄

• M _r = 354.17

• Monoclinic,

• a = 11.871 (2) Å

• b = 19.840 (4) Å

• c = 7.1983 (13) Å

• β = 124.488 (3)°

• V = 1397.4 (4) ų

• Z = 4

• Mo Kα radiation

• μ = 2.96 mm⁻¹

• T = 150 K

• 0.20 × 0.07 × 0.03 mm

Data collection

• Bruker SMART APEX CCD area-detector diffractometer

• Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.589, T _max = 0.916

• 5456 measured reflections

• 2680 independent reflections

• 1636 reflections with I > 2σ(I)

• R _int = 0.087

Refinement

• R[F ² > 2σ(F ²)] = 0.061

• wR(F ²) = 0.119

• S = 0.86

• 2680 reflections

• 191 parameters

• 2 restraints

• H-atom parameters constrained

• Δρ_max = 0.66 e Å⁻³

• Δρ_min = −0.55 e Å⁻³

• Absolute structure: Flack (1983 ▶), 1301 Friedel pairs

• Flack parameter: 0.091 (17)

Data collection: SMART (Bruker, 2001 ▶); cell refinement: SAINT (Bruker, 1999 ▶); data reduction: SAINT; 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.

Supplementary Material

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⋯O2i	0.99	2.59	3.494 (10)	152

Symmetry code: (i) .

supplementary crystallographic information

Comment

Derivatives of benzoic acid offer promise as compounds that possess multifunctional physiological activity (hypolesterolemic, antitumor, antithrombic, etc.) and do not cause hypervitaminosis and other side-effects (Jetten et al. 1987). It has been reported that synthesized benzoic acid derivatives of the amide- and chalcone-series show inhibitory activity of squamous cell differentiation of rabbit traeheal epithelial cell but induce differentiation of mouse embryonal carcinoma F9 and human promyelocytic leukemia HL60 cells (Correa-Basurto et al., 2005). p-Aminobenzoic acid derivatives were evaluated as acetylcholinesterase inhibitors (AChEIs) (Sato et al., 2005). Benzoic acid derivatives have also been found to exhibit cytotoxic effects on the MDA-MB-435-S—F breast cancer cell line (Kelly et al., 2007).

In the crystal structure of the title compound (I), Fig. 1, the key C=O and C—N bond distances are in agreement with those observed in the related structure of imidazolmethyl phthalimide (Wang et al., 2008).

Experimental

Metronidazole (5 g, 29.23 mmol) was added to 3-bromobenzoic acid (7.64 g, 38.01 mmol) dissolved in anhydrous CH₂Cl₂ (10 ml). Then 4-dimethylaminopyridine (0.15 equiv.) and dicyclohexylcarbodiimide (1.25 equiv) were added, and the resulting solution stirred. After 12 h, the solvent was evaporated under reduced pressure. The crude reaction mixture was subjected to flash column chromatography over silica gel, successively eluting with n-hexane–ethyl acetate (3:7) which afforded (I) in 70% yield. Colorless crystals were obtained from the slow evaporation of a CH₂Cl₂ solution of (I).

Refinement

H atoms were placed in calculated positions, C—H = 0.95–0.99 Å, and included in the riding model approximation with U_iso set to 1.5U_eq(C) for methyl-H atoms and 1.2U_eq(C) for remaining H atoms.

Figures

Fig. 1.

Molecular Structure of (I) show atom labelling and 30% displacement ellipsoids.

Crystal data

C13H12BrN3O4	F(000) = 712
Mr = 354.17	Dx = 1.683 Mg m−3
Monoclinic, Cc	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C -2yc	Cell parameters from 616 reflections
a = 11.871 (2) Å	θ = 3.7–23.3°
b = 19.840 (4) Å	µ = 2.96 mm−1
c = 7.1983 (13) Å	T = 150 K
β = 124.488 (3)°	Needle, colourless
V = 1397.4 (4) Å3	0.20 × 0.07 × 0.03 mm
Z = 4

Data collection

Bruker APEX 2000 CCD area-detector diffractometer	2680 independent reflections
Radiation source: fine-focus sealed tube	1636 reflections with I > 2σ(I)
graphite	Rint = 0.087
φ and ω scans	θmax = 26.0°, θmin = 2.1°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −14→14
Tmin = 0.589, Tmax = 0.916	k = −24→23
5456 measured reflections	l = −8→8

Refinement

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.061	H-atom parameters constrained
wR(F2) = 0.119	w = 1/[σ2(Fo2) + (0.0345P)2] where P = (Fo2 + 2Fc2)/3
S = 0.86	(Δ/σ)max = 0.001
2680 reflections	Δρmax = 0.66 e Å−3
191 parameters	Δρmin = −0.55 e Å−3
2 restraints	Absolute structure: Flack (1983), 1301 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: 0.091 (17)

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
Br1	0.81001 (10)	0.59782 (5)	0.72927 (13)	0.0588 (3)
O1	0.0138 (5)	0.6343 (3)	0.5323 (9)	0.0363 (14)
O2	0.0896 (5)	0.7074 (3)	0.8019 (9)	0.0434 (15)
O3	0.2933 (5)	0.5475 (3)	0.4184 (9)	0.0309 (14)
O4	0.2623 (6)	0.4375 (3)	0.4381 (11)	0.0437 (16)
N1	0.0966 (6)	0.6786 (3)	0.6597 (11)	0.0322 (16)
N2	0.2152 (6)	0.6769 (3)	0.4669 (9)	0.0234 (14)
N3	0.3904 (6)	0.7449 (3)	0.6962 (11)	0.0324 (16)
C1	0.2023 (8)	0.6976 (4)	0.6362 (12)	0.0261 (17)
C2	0.3074 (10)	0.7391 (4)	0.7650 (18)	0.042 (3)
H2	0.3216	0.7622	0.8924	0.050*
C3	0.3307 (8)	0.7090 (4)	0.5099 (13)	0.0281 (18)
C4	0.1261 (7)	0.6329 (4)	0.2730 (12)	0.0280 (18)
H4A	0.1413	0.6422	0.1537	0.034*
H4B	0.0295	0.6436	0.2115	0.034*
C5	0.1513 (7)	0.5597 (4)	0.3332 (13)	0.0294 (19)
H5A	0.1344	0.5490	0.4498	0.035*
H5B	0.0903	0.5315	0.1988	0.035*
C6	0.3328 (8)	0.4832 (4)	0.4592 (12)	0.0222 (18)
C7	0.4765 (8)	0.4759 (4)	0.5349 (12)	0.0263 (19)
C8	0.5272 (9)	0.4134 (4)	0.5409 (13)	0.041 (2)
H8	0.4686	0.3754	0.4966	0.049*
C9	0.6614 (10)	0.4036 (5)	0.6098 (14)	0.048 (2)
H9	0.6962	0.3596	0.6198	0.057*
C10	0.7422 (9)	0.4597 (5)	0.6630 (13)	0.049 (3)
H10	0.8333	0.4538	0.7053	0.059*
C11	0.6978 (8)	0.5231 (4)	0.6579 (12)	0.035 (2)
C12	0.5625 (7)	0.5325 (4)	0.5850 (12)	0.032 (2)
H12	0.5277	0.5768	0.5688	0.038*
C13	0.3796 (8)	0.7029 (4)	0.3597 (13)	0.043 (2)
H13A	0.3319	0.7359	0.2373	0.064*
H13B	0.3608	0.6573	0.2962	0.064*
H13C	0.4781	0.7115	0.4472	0.064*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
Br1	0.0321 (4)	0.0955 (8)	0.0384 (5)	−0.0218 (7)	0.0137 (4)	0.0017 (7)
O1	0.025 (3)	0.046 (4)	0.035 (3)	−0.002 (3)	0.014 (3)	0.006 (3)
O2	0.038 (3)	0.065 (4)	0.039 (3)	0.001 (3)	0.028 (3)	−0.007 (3)
O3	0.025 (3)	0.031 (3)	0.036 (4)	0.002 (3)	0.017 (3)	0.005 (3)
O4	0.042 (4)	0.031 (3)	0.062 (4)	−0.003 (3)	0.032 (4)	0.005 (3)
N1	0.021 (4)	0.044 (4)	0.030 (4)	0.007 (3)	0.014 (3)	0.013 (3)
N2	0.025 (4)	0.028 (4)	0.018 (3)	−0.009 (3)	0.012 (3)	−0.003 (3)
N3	0.031 (4)	0.036 (4)	0.036 (4)	−0.007 (3)	0.022 (4)	−0.012 (3)
C1	0.024 (4)	0.031 (4)	0.025 (4)	−0.005 (4)	0.015 (4)	−0.006 (4)
C2	0.030 (5)	0.030 (5)	0.059 (7)	0.003 (5)	0.021 (5)	0.000 (5)
C3	0.035 (5)	0.024 (4)	0.030 (5)	0.006 (4)	0.021 (4)	0.008 (4)
C4	0.027 (4)	0.039 (5)	0.022 (4)	−0.005 (4)	0.017 (4)	0.000 (4)
C5	0.021 (4)	0.043 (5)	0.028 (5)	−0.003 (4)	0.017 (4)	0.008 (4)
C6	0.027 (5)	0.028 (5)	0.010 (4)	−0.004 (4)	0.010 (3)	−0.002 (4)
C7	0.024 (4)	0.037 (5)	0.019 (4)	0.005 (4)	0.013 (4)	−0.002 (4)
C8	0.044 (6)	0.046 (6)	0.024 (5)	0.004 (5)	0.014 (4)	0.003 (4)
C9	0.049 (6)	0.049 (6)	0.041 (6)	0.022 (5)	0.023 (5)	0.011 (5)
C10	0.038 (5)	0.085 (8)	0.035 (6)	0.012 (5)	0.027 (5)	0.012 (5)
C11	0.029 (5)	0.050 (6)	0.021 (4)	0.005 (4)	0.011 (4)	0.000 (4)
C12	0.025 (4)	0.045 (5)	0.021 (4)	0.009 (4)	0.010 (4)	0.009 (4)
C13	0.053 (6)	0.043 (5)	0.044 (5)	−0.010 (5)	0.035 (5)	0.006 (4)

Geometric parameters (Å, °)

Br1—C11	1.861 (8)	C4—H4B	0.9900
O1—N1	1.248 (7)	C5—H5A	0.9900
O2—N1	1.216 (8)	C5—H5B	0.9900
O3—C6	1.334 (9)	C6—C7	1.475 (10)
O3—C5	1.451 (8)	C7—C8	1.369 (10)
O4—C6	1.183 (9)	C7—C12	1.420 (11)
N1—C1	1.410 (9)	C8—C9	1.389 (12)
N2—C1	1.374 (9)	C8—H8	0.9500
N2—C3	1.378 (9)	C9—C10	1.375 (11)
N2—C4	1.468 (8)	C9—H9	0.9500
N3—C3	1.317 (9)	C10—C11	1.356 (11)
N3—C2	1.334 (11)	C10—H10	0.9500
C1—C2	1.336 (12)	C11—C12	1.391 (10)
C2—H2	0.9500	C12—H12	0.9500
C3—C13	1.493 (10)	C13—H13A	0.9800
C4—C5	1.497 (10)	C13—H13B	0.9800
C4—H4A	0.9900	C13—H13C	0.9800
C6—O3—C5	115.6 (6)	H5A—C5—H5B	108.7
O2—N1—O1	123.3 (6)	O4—C6—O3	124.8 (7)
O2—N1—C1	117.7 (7)	O4—C6—C7	124.0 (8)
O1—N1—C1	119.0 (6)	O3—C6—C7	111.3 (7)
C1—N2—C3	105.0 (6)	C8—C7—C12	118.0 (7)
C1—N2—C4	129.7 (6)	C8—C7—C6	119.7 (8)
C3—N2—C4	125.2 (6)	C12—C7—C6	122.1 (7)
C3—N3—C2	104.3 (7)	C7—C8—C9	122.2 (8)
C2—C1—N2	105.7 (7)	C7—C8—H8	118.9
C2—C1—N1	128.8 (8)	C9—C8—H8	118.9
N2—C1—N1	125.4 (6)	C10—C9—C8	117.7 (8)
N3—C2—C1	113.0 (9)	C10—C9—H9	121.1
N3—C2—H2	123.5	C8—C9—H9	121.1
C1—C2—H2	123.5	C11—C10—C9	122.9 (8)
N3—C3—N2	111.8 (6)	C11—C10—H10	118.5
N3—C3—C13	125.1 (7)	C9—C10—H10	118.5
N2—C3—C13	123.0 (7)	C10—C11—C12	118.9 (8)
N2—C4—C5	112.5 (6)	C10—C11—Br1	121.6 (7)
N2—C4—H4A	109.1	C12—C11—Br1	119.3 (6)
C5—C4—H4A	109.1	C11—C12—C7	120.0 (8)
N2—C4—H4B	109.1	C11—C12—H12	120.0
C5—C4—H4B	109.1	C7—C12—H12	120.0
H4A—C4—H4B	107.8	C3—C13—H13A	109.5
O3—C5—C4	106.1 (6)	C3—C13—H13B	109.5
O3—C5—H5A	110.5	H13A—C13—H13B	109.5
C4—C5—H5A	110.5	C3—C13—H13C	109.5
O3—C5—H5B	110.5	H13A—C13—H13C	109.5
C4—C5—H5B	110.5	H13B—C13—H13C	109.5
C3—N2—C1—C2	−0.1 (8)	C6—O3—C5—C4	−173.1 (6)
C4—N2—C1—C2	−177.6 (7)	N2—C4—C5—O3	−59.7 (7)
C3—N2—C1—N1	178.8 (7)	C5—O3—C6—O4	−2.7 (11)
C4—N2—C1—N1	1.3 (12)	C5—O3—C6—C7	177.4 (6)
O2—N1—C1—C2	7.5 (12)	O4—C6—C7—C8	13.3 (12)
O1—N1—C1—C2	−173.8 (8)	O3—C6—C7—C8	−166.7 (7)
O2—N1—C1—N2	−171.2 (7)	O4—C6—C7—C12	−172.0 (7)
O1—N1—C1—N2	7.5 (10)	O3—C6—C7—C12	8.0 (10)
C3—N3—C2—C1	3.8 (10)	C12—C7—C8—C9	4.8 (12)
N2—C1—C2—N3	−2.3 (10)	C6—C7—C8—C9	179.8 (7)
N1—C1—C2—N3	178.8 (7)	C7—C8—C9—C10	−3.0 (13)
C2—N3—C3—N2	−3.8 (9)	C8—C9—C10—C11	2.2 (13)
C2—N3—C3—C13	176.0 (8)	C9—C10—C11—C12	−3.3 (13)
C1—N2—C3—N3	2.5 (8)	C9—C10—C11—Br1	−179.6 (6)
C4—N2—C3—N3	−179.8 (6)	C10—C11—C12—C7	5.1 (11)
C1—N2—C3—C13	−177.3 (7)	Br1—C11—C12—C7	−178.5 (6)
C4—N2—C3—C13	0.3 (11)	C8—C7—C12—C11	−5.8 (11)
C1—N2—C4—C5	−81.4 (9)	C6—C7—C12—C11	179.4 (7)
C3—N2—C4—C5	101.6 (8)

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
C4—H4a···O2i	0.99	2.59	3.494 (10)	152

Symmetry codes: (i) x, y, z−1.