1-(4-Chloro­phenyl)-2-methyl-4-nitro-5-(1-piperidyl)-1H-imidazole

The only specific inter­actions that influence the crystal packing of the title compound, C₁₅H₁₇ClN₄O₂, are weak C-H...N and C-H...Cl hydrogen bonds, even though there is a possibility of, for example, [pi]-[pi] stacking or halogen bonding. The dihedral angle between the mean planes of the imidazole and benzene rings is 59.82 (5)°. The length of the C-N bond connecting the imidazole and piperidine fragments is correlated with the degree of pyramidalization of the piperidine N atom.

S1. Comment

Nitroimidazoles have been intensively investigated as radiosensitizers of hypoxic tumour cells and as veterinary drugs (Smithen & Hardy, 1982). In particular, 4-nitro-5-aminoimidazole derivatives have been relatively widely studied, due to their expected radiosensitizing activity combined with good water solubility (see, for example, Wolska et al., 1993, 1994). More recently, in the crystal structure of 1,2-dimethyl-4-nitro-5-morpholinylimidazole hydrate, the interesting case of centro–noncentro ambiguity was found (Kubicki et al., 2003). Moreover, a number of simple 4-nitroimidazole derivatives have been used for studying different intermolecular interactions (see, for example, Kubicki, 2005, and references therein). The structure of another 4-nitro-5-aminoimidazole, the title compound, (I), is reported here. The ability of 4-nitroimidazoles to undergo nucleophilic substitution has been widely investigated (see, for example, M\,akosza, 1992) and provides a convenient way of modifying azole derivatives. Some amino derivatives have also been synthesized in this way (M\,akosza & Białecki, 1998; Suwiński & Świerczek, 1996).

Fig. 1 shows a displacement ellipsoid representation of (I). The benzene and imidazole rings are almost perfectly planar, the maximum deviations from the least-squares planes being not larger than 0.015 (1) Å. The dihedral angle between the mean planes of these rings is 59.82 (5)°. The nitro group is also significantly twisted out of the imidazole plane, the dihedral angle between the appropriate planes being 14.7 (2)°. This value is larger than in similar compounds and is probably caused by the presence of the bulky substituent at position 5. The C—N—O angles are asymmetric, and this asymmetry is typical of 5-substituted 4-nitroimidazole derivatives (Kubicki, 2004a). The C4—N4—O41 angle (cis with respect to imidazole ring atom N3) is smaller than the angle trans to N3 (C4—N4—O42) by 1.1°. For 5-H derivatives, this asymmetry in C—N—O angles is also observed, but in reverse: the cis angle is larger than the trans one (Kubicki, 2004b).

The molecular geometry of (I) is quite typical. In this type of compound, there is an interesting correlation between the C5—N51 bond length and the sum of the bond angles around N51: the longer the bond, the larger is the pyramidalization of the N atom, i.e. the smaller the sum of the bond angles. For 16 fragments of 5-(cyclic)amino imidazoles found in the CSD (November 2004 version, February 2005 updates; Allen, 2002), the correlation coefficient is 0.98 (Fig. 2), and the data for (I) fit perfectly into this relation. It might also be noted that there is no such correlation between the C5—N51 bond length and the angles around atom C5.

The piperidine ring is in a chair conformation. The asymmetry parameters (Duax & Norton, 1975) show only minor distortions from the ideal C_3d symmetry (maximum value of the ΔC₂ parameter is 3.83°, and of ΔC_s −3.15°).

In the crystal structure of (I), there are infinite chains of molecules extending along the [100] direction, created by C—H···N3 hydrogen bonds. Using graph-set notation (Etter et al., 1990; Bernstein et al., 1995), this motif can be described as a C(7) chain. Neighbouring chains are connected by weak three-centred C—H···Cl hydrogen bonds {C(12)[R₂¹(5)] chains along the [001] direction}. These two kinds of weak interactions close larger rings of molecules of motif R₄⁴(30) (Fig. 3). The geometric details of these interactions are given in Table 2. Interestingly, in this case no other specific interatomic interactions (e.g. π–π stacking or halogen bonds) take part in the creation of the supramolecular structure, even though these interactions could compete succesfully with weak hydrogen bonding.

S2. Experimental

The title compound was synthesized by nucleophilic replacement of bromine at the 5-position of the imidazole ring by piperidine (see scheme). The reaction was carried out in boiling methanol with an excess of piperidine over 24 h with a high yield. In contrast with the reactivity of the 1-alkyl derivative, in which double substitution of the bromo and nitro groups was observed (Kulkarni et al., 1987), the arene substituent significantly decreases the reactivity of the imidazole moiety. Crystals of (I) for X-ray data collection were grown from a methanol solution.

S3. Refinement

The positions of the H atoms were freely refined. For each group of these atoms, i.e. for the methyl group, for each CH₂ group and for ring H atoms, one common U_iso(H) parameter was refined.

Computing details

Data collection: CrysAlis CCD (Oxford Diffraction, 2002); cell refinement: CrysAlis CCD; data reduction: CrysAlis RED (Oxford Diffraction, 2002); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: Stereochemical Workstation Operation Manual (Siemens, 1989); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. A view of the molecule of (I), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. A correlation between the C—N bond length and the sum of the valence angles around the amino N atom for 5-(cyclic)aminoimidazoles.
	Fig. 3. The crystal packing of (I), viewed approximately along the [010] direction. Hydrogen bonds are depicted as dashed lines. [Symmetry codes: (iii) −1 + x, y, z; (iv) 3/2 − x, −y, 1/2 + z; (v) 3/2 − x, −y, 1/2 + z; (vi) 5/2 − x, −y, 1/2 + z; (vii) 1/2 − x, −y, −1/2 + z; (viii) 5/2 − x, −y, −1/2 + z. For other symmetry codes, see Table 2.]

1-(4-Chlorophenyl)-2-methyl-4-nitro-5-(1-piperidyl)-1H-imidazole

Crystal data

C15H17ClN4O2	F(000) = 672
Mr = 320.78	Dx = 1.466 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 2320 reflections
a = 8.5841 (12) Å	θ = 3–20°
b = 9.0352 (12) Å	µ = 0.28 mm^−1
c = 18.738 (2) Å	T = 90 K
V = 1453.3 (3) Å^3	Needle, colourless
Z = 4	0.4 × 0.15 × 0.1 mm

Data collection

Kuma KM4 CCD four-circle diffractometer	4072 independent reflections
Radiation source: fine-focus sealed tube	3298 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.027
ω scans	θmax = 30.0°, θmin = 3.1°
Absorption correction: multi-scan (SORTAV; Blessing, 1989)	h = −12→12
Tmin = 0.958, Tmax = 0.972	k = −12→12
15516 measured reflections	l = −25→23

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.031	All H-atom parameters refined
wR(F^2) = 0.054	w = 1/[σ^2(Fo^2) + (0.021P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 0.93	(Δ/σ)max = 0.008
4069 reflections	Δρmax = 0.25 e Å^−3
257 parameters	Δρmin = −0.22 e Å^−3
0 restraints	Absolute structure: Flack (1983), with how many Friedel pairs?
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.03 (4)

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
N1	0.19042 (12)	0.07948 (15)	0.71631 (6)	0.0126 (3)
C11	0.33192 (15)	0.04219 (17)	0.75320 (8)	0.0124 (3)
C12	0.47264 (15)	0.09400 (18)	0.72753 (8)	0.0137 (3)
H12	0.4765 (17)	0.1533 (18)	0.6841 (9)	0.019 (2)*
C13	0.60879 (15)	0.05860 (18)	0.76298 (8)	0.0157 (3)
H13	0.7086 (17)	0.0936 (17)	0.7448 (8)	0.019 (2)*
C14	0.59994 (16)	−0.02462 (17)	0.82484 (8)	0.0150 (3)
Cl14	0.76976 (4)	−0.07192 (5)	0.86936 (2)	0.02338 (10)
C15	0.45927 (15)	−0.07465 (19)	0.85163 (8)	0.0142 (3)
H15	0.4595 (18)	−0.1330 (18)	0.8939 (9)	0.019 (2)*
C16	0.32332 (17)	−0.04355 (18)	0.81422 (8)	0.0140 (3)
H16	0.2236 (17)	−0.0833 (18)	0.8289 (8)	0.019 (2)*
C2	0.06975 (15)	0.16119 (17)	0.74527 (8)	0.0148 (3)
C21	0.07373 (19)	0.2204 (2)	0.81911 (9)	0.0213 (4)
H21A	−0.010 (2)	0.293 (2)	0.8260 (10)	0.045 (3)*
H21B	0.165 (2)	0.271 (2)	0.8307 (10)	0.045 (3)*
H21C	0.056 (2)	0.140 (2)	0.8538 (11)	0.045 (3)*
N3	−0.04125 (14)	0.18348 (15)	0.69922 (7)	0.0159 (3)
C4	0.00696 (15)	0.11221 (17)	0.63817 (8)	0.0144 (3)
N4	−0.09856 (13)	0.09276 (15)	0.58097 (7)	0.0178 (3)
O41	−0.22275 (12)	0.16262 (13)	0.58280 (6)	0.0239 (3)
O42	−0.06557 (12)	0.00420 (14)	0.53316 (6)	0.0246 (3)
C5	0.15393 (14)	0.04953 (17)	0.64545 (8)	0.0133 (3)
N51	0.25744 (14)	−0.01388 (14)	0.59974 (6)	0.0143 (3)
C52	0.32780 (17)	−0.15815 (18)	0.61540 (8)	0.0149 (3)
H52A	0.2683 (18)	−0.2385 (17)	0.5884 (8)	0.016 (3)*
H52B	0.3182 (17)	−0.1755 (18)	0.6671 (9)	0.016 (3)*
C53	0.49641 (17)	−0.1627 (2)	0.59020 (9)	0.0173 (3)
H53A	0.5566 (18)	−0.098 (2)	0.6202 (9)	0.024 (3)*
H53B	0.5392 (19)	−0.263 (2)	0.5973 (9)	0.024 (3)*
C54	0.50843 (18)	−0.1180 (2)	0.51212 (9)	0.0195 (4)
H54A	0.4547 (17)	−0.1915 (18)	0.4839 (8)	0.015 (3)*
H54B	0.6182 (17)	−0.1056 (17)	0.4983 (8)	0.015 (3)*
C55	0.43086 (17)	0.0315 (2)	0.49973 (9)	0.0180 (4)
H55A	0.4873 (17)	0.1138 (19)	0.5230 (8)	0.018 (3)*
H55B	0.4351 (16)	0.0596 (19)	0.4499 (9)	0.018 (3)*
C56	0.26227 (17)	0.02967 (19)	0.52466 (8)	0.0170 (3)
H56A	0.2142 (17)	0.1267 (18)	0.5202 (8)	0.019 (3)*
H56B	0.2013 (17)	−0.0394 (18)	0.4944 (8)	0.019 (3)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0101 (5)	0.0132 (7)	0.0145 (6)	0.0013 (5)	0.0005 (4)	0.0004 (6)
C11	0.0098 (5)	0.0126 (9)	0.0149 (7)	0.0011 (5)	−0.0003 (5)	−0.0021 (6)
C12	0.0146 (6)	0.0117 (8)	0.0148 (8)	−0.0019 (6)	0.0011 (5)	−0.0005 (7)
C13	0.0120 (6)	0.0145 (9)	0.0205 (8)	−0.0006 (6)	0.0005 (5)	−0.0039 (7)
C14	0.0129 (6)	0.0135 (9)	0.0186 (8)	0.0029 (5)	−0.0052 (5)	−0.0060 (7)
Cl14	0.01719 (15)	0.0261 (2)	0.0268 (2)	0.00672 (16)	−0.00870 (15)	−0.00548 (19)
C15	0.0182 (6)	0.0109 (8)	0.0134 (7)	0.0024 (6)	0.0000 (5)	−0.0003 (7)
C16	0.0146 (6)	0.0136 (9)	0.0138 (7)	−0.0013 (6)	0.0008 (5)	−0.0026 (6)
C2	0.0113 (6)	0.0128 (9)	0.0205 (8)	0.0008 (5)	0.0034 (5)	0.0001 (7)
C21	0.0188 (8)	0.0254 (11)	0.0197 (9)	0.0066 (7)	0.0022 (6)	−0.0030 (8)
N3	0.0131 (6)	0.0170 (8)	0.0177 (7)	0.0020 (5)	0.0006 (5)	0.0013 (6)
C4	0.0115 (6)	0.0148 (9)	0.0170 (8)	−0.0005 (5)	−0.0007 (5)	0.0023 (7)
N4	0.0129 (5)	0.0192 (8)	0.0214 (7)	−0.0003 (6)	−0.0010 (5)	0.0031 (6)
O41	0.0130 (5)	0.0260 (7)	0.0326 (7)	0.0055 (5)	−0.0065 (5)	0.0005 (5)
O42	0.0189 (5)	0.0306 (8)	0.0245 (6)	0.0017 (5)	−0.0038 (5)	−0.0077 (6)
C5	0.0119 (6)	0.0112 (8)	0.0169 (8)	−0.0004 (5)	−0.0002 (5)	0.0016 (6)
N51	0.0136 (5)	0.0154 (7)	0.0139 (6)	0.0044 (5)	0.0017 (5)	0.0021 (5)
C52	0.0150 (6)	0.0133 (9)	0.0163 (8)	0.0006 (6)	0.0011 (6)	−0.0004 (7)
C53	0.0162 (7)	0.0171 (9)	0.0186 (9)	0.0050 (6)	0.0012 (6)	0.0011 (7)
C54	0.0187 (7)	0.0210 (10)	0.0187 (9)	0.0030 (6)	0.0046 (6)	−0.0002 (7)
C55	0.0179 (7)	0.0202 (10)	0.0160 (8)	0.0019 (6)	0.0030 (6)	0.0025 (7)
C56	0.0173 (7)	0.0200 (10)	0.0136 (7)	0.0030 (6)	−0.0003 (6)	0.0025 (6)

Geometric parameters (Å, º)

N1—C2	1.383 (2)	C4—N4	1.414 (2)
N1—C5	1.391 (2)	N4—O42	1.234 (2)
N1—C11	1.438 (2)	N4—O41	1.239 (2)
C11—C12	1.382 (2)	C5—N51	1.361 (2)
C11—C16	1.383 (2)	N51—C56	1.462 (2)
C12—C13	1.382 (2)	N51—C52	1.466 (2)
C12—H12	0.98 (2)	C52—C53	1.523 (2)
C13—C14	1.384 (2)	C52—H52A	1.02 (2)
C13—H13	0.97 (2)	C52—H52B	0.98 (2)
C14—C15	1.384 (2)	C53—C54	1.521 (2)
C14—Cl14	1.733 (1)	C53—H53A	0.96 (2)
C15—C16	1.390 (2)	C53—H53B	0.99 (2)
C15—H15	0.95 (2)	C54—C55	1.524 (2)
C16—H16	0.97 (2)	C54—H54A	0.97 (2)
C2—N3	1.301 (2)	C54—H54B	0.98 (2)
C2—C21	1.484 (2)	C55—C56	1.521 (2)
C21—H21A	0.98 (2)	C55—H55A	0.99 (2)
C21—H21B	0.93 (2)	C55—H55B	0.97 (2)
C21—H21C	0.99 (2)	C56—H56A	0.97 (2)
N3—C4	1.376 (2)	C56—H56B	0.99 (2)
C4—C5	1.390 (2)
C2—N1—C5	108.1 (1)	N51—C5—C4	134.7 (1)
C2—N1—C11	124.7 (1)	N51—C5—N1	122.4 (1)
C5—N1—C11	127.1 (1)	C4—C5—N1	102.6 (1)
C12—C11—C16	121.6 (1)	C5—N51—C56	120.7 (1)
C12—C11—N1	119.5 (1)	C5—N51—C52	121.2 (1)
C16—C11—N1	118.9 (1)	C56—N51—C52	114.9 (1)
C13—C12—C11	119.6 (1)	N51—C52—C53	110.7 (1)
C13—C12—H12	120.0 (9)	N51—C52—H52A	109.1 (9)
C11—C12—H12	120.4 (9)	C53—C52—H52A	107.6 (9)
C12—C13—C14	118.8 (1)	N51—C52—H52B	107.7 (9)
C12—C13—H13	120.0 (9)	C53—C52—H52B	112.3 (9)
C14—C13—H13	121.1 (9)	H52A—C52—H52B	109 (1)
C15—C14—C13	122.0 (1)	C54—C53—C52	110.8 (1)
C15—C14—Cl14	118.6 (1)	C54—C53—H53A	112 (1)
C13—C14—Cl14	119.4 (1)	C52—C53—H53A	108.3 (9)
C14—C15—C16	118.9 (1)	C54—C53—H53B	110 (1)
C14—C15—H15	118.8 (9)	C52—C53—H53B	110 (1)
C16—C15—H15	122 (1)	H53A—C53—H53B	106 (1)
C11—C16—C15	119.0 (1)	C53—C54—C55	110.6 (1)
C11—C16—H16	119.3 (9)	C53—C54—H54A	108.1 (9)
C15—C16—H16	121.6 (9)	C55—C54—H54A	108.5 (9)
N3—C2—N1	111.8 (1)	C53—C54—H54B	110.4 (9)
N3—C2—C21	125.4 (1)	C55—C54—H54B	106.1 (9)
N1—C2—C21	122.8 (1)	H54A—C54—H54B	113 (1)
C2—C21—H21A	110 (1)	C56—C55—C54	111.1 (1)
C2—C21—H21B	115 (1)	C56—C55—H55A	109.8 (9)
H21A—C21—H21B	105 (2)	C54—C55—H55A	112.7 (9)
C2—C21—H21C	110 (1)	C56—C55—H55B	109.6 (8)
H21A—C21—H21C	107 (2)	C54—C55—H55B	111 (1)
H21B—C21—H21C	110 (2)	H55A—C55—H55B	102 (1)
C2—N3—C4	105.0 (1)	N51—C56—C55	109.0 (1)
N3—C4—C5	112.5 (1)	N51—C56—H56A	108.3 (9)
N3—C4—N4	119.7 (1)	C55—C56—H56A	111.6 (9)
C5—C4—N4	127.2 (1)	N51—C56—H56B	111.5 (9)
O42—N4—O41	123.2 (1)	C55—C56—H56B	109.5 (8)
O42—N4—C4	118.9 (1)	H56A—C56—H56B	107 (1)
O41—N4—C4	117.8 (1)
C2—N1—C11—C12	−117.5 (2)	C5—C4—N4—O42	5.0 (2)
C5—N1—C11—C12	58.1 (2)	N3—C4—N4—O41	12.1 (2)
C2—N1—C11—C16	61.7 (2)	C5—C4—N4—O41	−177.4 (1)
C5—N1—C11—C16	−122.6 (2)	N3—C4—C5—N51	−170.3 (2)
C16—C11—C12—C13	0.6 (2)	N4—C4—C5—N51	18.7 (3)
N1—C11—C12—C13	179.9 (2)	N3—C4—C5—N1	3.1 (2)
C11—C12—C13—C14	−1.9 (2)	N4—C4—C5—N1	−167.9 (1)
C12—C13—C14—C15	0.8 (2)	C2—N1—C5—N51	172.0 (1)
C12—C13—C14—Cl14	179.2 (1)	C11—N1—C5—N51	−4.3 (2)
C13—C14—C15—C16	1.7 (2)	C2—N1—C5—C4	−2.5 (2)
Cl14—C14—C15—C16	−176.8 (1)	C11—N1—C5—C4	−178.7 (1)
C12—C11—C16—C15	1.8 (2)	C4—C5—N51—C56	28.5 (2)
N1—C11—C16—C15	−177.4 (1)	N1—C5—N51—C56	−143.9 (2)
C14—C15—C16—C11	−3.0 (2)	C4—C5—N51—C52	−130.1 (2)
C5—N1—C2—N3	1.1 (2)	N1—C5—N51—C52	57.5 (2)
C11—N1—C2—N3	177.4 (1)	C5—N51—C52—C53	−143.6 (1)
C5—N1—C2—C21	−176.3 (2)	C56—N51—C52—C53	56.7 (2)
C11—N1—C2—C21	0.1 (2)	N51—C52—C53—C54	−53.0 (2)
N1—C2—N3—C4	0.9 (2)	C52—C53—C54—C55	53.8 (2)
C21—C2—N3—C4	178.1 (2)	C53—C54—C55—C56	−55.9 (2)
C2—N3—C4—C5	−2.6 (2)	C5—N51—C56—C55	142.4 (1)
C2—N3—C4—N4	169.2 (1)	C52—N51—C56—C55	−57.8 (2)
N3—C4—N4—O42	−165.5 (1)	C54—C55—C56—N51	56.3 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C13—H13···N3^i	0.97 (2)	2.45 (2)	3.424 (2)	180 (1)
C54—H54B···Cl14^ii	0.98 (2)	3.06 (2)	3.705 (2)	125 (1)
C55—H55B···Cl14^ii	0.97 (2)	2.95 (1)	3.564 (2)	122 (1)

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