1-(3-Fluoro­phen­yl)-3-(4-nitro­phen­yl)urea

Abstract

In the title compound, C₁₃H₁₀FN₃O₃, the dihedral angle between the fluoro­phenyl and nitro­phenyl ring planes is 6.51 (9)°. The crystal structure features N—H⋯O hydrogen bonds.

Related literature  

The title compound is an activated fragment of sorafenib derivatives. Sorafenib is a VEGFR-2 inhibitor (Ferrara et al., 2003 ▶; Peruzzi et al., 2006 ▶) that has good therapeutic effect for renal carcinoma and liver cancer (Wan et al., 2004 ▶; Wilhelm et al., 2004 ▶).

Experimental  

Crystal data  

• C₁₃H₁₀FN₃O₃

• M _r = 275.24

• Monoclinic,

• a = 8.351 (4) Å

• b = 12.461 (6) Å

• c = 11.912 (6) Å

• β = 100.315 (9)°

• V = 1219.5 (11) ų

• Z = 4

• Mo Kα radiation

• μ = 0.12 mm⁻¹

• T = 113 K

• 0.24 × 0.22 × 0.20 mm

Data collection  

• Rigaku Saturn CCD area-detector diffractometer

• Absorption correction: multi-scan CrystalClear T _min = 0.972, T _max = 0.977

• 12466 measured reflections

• 2900 independent reflections

• 2459 reflections with I > 2σ(I)

• R _int = 0.045

Refinement  

• R[F ² > 2σ(F ²)] = 0.052

• wR(F ²) = 0.131

• S = 1.12

• 2900 reflections

• 189 parameters

• 2 restraints

• H atoms treated by a mixture of independent and constrained refinement

• Δρ_max = 0.30 e Å⁻³

• Δρ_min = −0.26 e Å⁻³

Data collection: CrystalClear (Rigaku, 2005 ▶); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL/PC (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL/PC.

Supplementary Material

Supplementary material file. DOI: 10.1107/S160053681202507X/zj2072Isup3.cml

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
N2—H2A⋯O1i	0.91 (1)	1.99 (1)	2.890 (2)	170 (2)
N3—H3A⋯O2i	0.90 (1)	2.28 (1)	3.157 (2)	168 (2)

Symmetry code: (i) .

supplementary crystallographic information

Comment

Sorafenib is a VEGFR-2 inhibitor (Ferrara et al., 2003; Peruzzi et al., 2006) that has good therapeutic effect for renal carcinoma and liver cancer (Wan et al., 2004; Wilhelm et al., 2004). 1-(3-fluorophenyl)-3-(4-nitrophenyl) urea is an important activated fragment of sorafenib derivatives. We present here the structure characterization of the title compound.

In the molecule of the title compound (Fig.1) bond lengths and angles have normal values. The interplanar angle between the fluorobenzyl and nitrobenzyl ring planes is 6.51 (9)°. The crystal structure is stabilized by the intermolecular N—H···O hydrogen bonds. The crystal structure (Fig.2) is stabilized by intermolecular N—H···O hydrogen bonds (table 1).

Experimental

A solution of 4-nitroaniline (1.38 g, 10 mmol) in DCM (100 ml) was added dropwise to a stirred solution of bis(trichloromethyl) carbonate (5.92 g, 20 mmol) in DCM (20 ml) at the atmosphere of ice-bath.The reaction mixture was stirred for 2 hrs at 0–5°C. Then the reaction mixture was added drpwise to a refluxed and stirred solution of 3-fluoroaniline (1.11 g, 10 mmol) in DCM (40 ml).The reaction was completed within 2 hrs at the reflux temperature.The solvent was removed under reduced pressure.Acetone (100 ml) and H₂O (300 ml) was added to the mixture. The solid was collected and washed with H₂O,then gave a yellow solid. The yield was 2.08 g (75.6%). Put about 0.3 g of the product in the ampoule bottle and add 10 ml absolute ethyl alcohol, yellow single crystals suitable for X-ray diffraction analysis were obtained by slow evaporation of the solvent at room temperature after 3 weeks.

Refinement

All H atoms were detected in a difference map, nevertheless, the H-atoms attached to the nitrogen atoms were refined freely, and the H-atoms attached to the carbon atoms were placed in calculated positions and refined using a riding motion approximation, with C—H=0.95 Å, with U_iso(H)=1.2U_eq(C).

Figures

Fig. 1.

The molecular structure of the title compound, showing the atomic numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.

Fig. 2.

Packing diagram of the title compound viewed along the c axis. Hydrogen bonds are shown as dashed lines.

Crystal data

C13H10FN3O3	F(000) = 568
Mr = 275.24	Dx = 1.499 Mg m−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 4180 reflections
a = 8.351 (4) Å	θ = 1.6–27.8°
b = 12.461 (6) Å	µ = 0.12 mm−1
c = 11.912 (6) Å	T = 113 K
β = 100.315 (9)°	Prism, yellow
V = 1219.5 (11) Å3	0.24 × 0.22 × 0.20 mm
Z = 4

Data collection

Rigaku Saturn CCD area-detector diffractometer	2900 independent reflections
Radiation source: rotating anode	2459 reflections with I > 2σ(I)
Multilayer monochromator	Rint = 0.045
Detector resolution: 14.63 pixels mm-1	θmax = 27.8°, θmin = 2.4°
ω and φ scans	h = −10→10
Absorption correction: multi-scan CrystalClear	k = −16→16
Tmin = 0.972, Tmax = 0.977	l = −15→15
12466 measured reflections

Refinement

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)] = 0.052	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.131	H atoms treated by a mixture of independent and constrained refinement
S = 1.12	w = 1/[σ2(Fo2) + (0.063P)2 + 0.1263P] where P = (Fo2 + 2Fc2)/3
2900 reflections	(Δ/σ)max = 0.003
189 parameters	Δρmax = 0.30 e Å−3
2 restraints	Δρmin = −0.26 e Å−3

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
F1	0.29184 (14)	0.96861 (8)	−0.02312 (9)	0.0449 (3)
O1	−0.04969 (14)	0.17411 (10)	0.34582 (10)	0.0322 (3)
O2	0.01132 (14)	0.04318 (10)	0.24132 (10)	0.0340 (3)
O3	0.19105 (13)	0.60131 (9)	0.05581 (9)	0.0277 (3)
N1	0.01105 (16)	0.13960 (12)	0.26533 (12)	0.0265 (3)
N2	0.26220 (16)	0.43681 (11)	−0.00884 (11)	0.0255 (3)
N3	0.32644 (17)	0.58967 (11)	−0.09569 (11)	0.0258 (3)
C1	0.20093 (18)	0.36633 (13)	0.06336 (13)	0.0236 (3)
C2	0.19815 (19)	0.25683 (13)	0.03495 (13)	0.0252 (4)
H2	0.2380	0.2346	−0.0312	0.030*
C3	0.13910 (19)	0.18127 (13)	0.10071 (14)	0.0264 (4)
H3	0.1371	0.1074	0.0808	0.032*
C4	0.08209 (18)	0.21605 (13)	0.19783 (13)	0.0232 (3)
C5	0.08776 (19)	0.32275 (13)	0.22924 (14)	0.0258 (4)
H5	0.0505	0.3439	0.2967	0.031*
C6	0.14717 (19)	0.39910 (13)	0.16335 (13)	0.0258 (4)
H6	0.1517	0.4725	0.1852	0.031*
C7	0.25437 (18)	0.54780 (13)	−0.01016 (13)	0.0234 (3)
C8	0.35025 (18)	0.69898 (13)	−0.11978 (13)	0.0246 (4)
C9	0.42473 (19)	0.72135 (14)	−0.21284 (14)	0.0268 (4)
H9	0.4554	0.6642	−0.2573	0.032*
C10	0.4543 (2)	0.82664 (14)	−0.24089 (14)	0.0297 (4)
H10	0.5056	0.8406	−0.3044	0.036*
C11	0.4106 (2)	0.91169 (15)	−0.17805 (15)	0.0327 (4)
H11	0.4305	0.9840	−0.1969	0.039*
C12	0.3367 (2)	0.88660 (13)	−0.08702 (15)	0.0307 (4)
C13	0.30351 (19)	0.78355 (14)	−0.05540 (14)	0.0274 (4)
H13	0.2509	0.7705	0.0077	0.033*
H2A	0.314 (2)	0.4069 (14)	−0.0618 (13)	0.037 (5)*
H3A	0.372 (2)	0.5429 (15)	−0.1377 (15)	0.056 (7)*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
F1	0.0653 (8)	0.0268 (6)	0.0451 (7)	−0.0026 (5)	0.0172 (6)	−0.0077 (5)
O1	0.0318 (6)	0.0391 (7)	0.0288 (7)	−0.0028 (5)	0.0136 (5)	0.0027 (5)
O2	0.0370 (7)	0.0269 (6)	0.0393 (7)	−0.0018 (5)	0.0096 (5)	0.0044 (5)
O3	0.0300 (6)	0.0275 (6)	0.0278 (6)	0.0027 (5)	0.0116 (5)	−0.0012 (5)
N1	0.0231 (7)	0.0283 (7)	0.0281 (7)	−0.0001 (6)	0.0044 (5)	0.0032 (6)
N2	0.0292 (7)	0.0241 (7)	0.0265 (7)	0.0010 (6)	0.0141 (6)	0.0009 (6)
N3	0.0303 (7)	0.0235 (7)	0.0265 (7)	0.0016 (6)	0.0130 (6)	0.0012 (6)
C1	0.0206 (7)	0.0276 (8)	0.0236 (8)	0.0013 (6)	0.0060 (6)	0.0015 (6)
C2	0.0259 (8)	0.0284 (8)	0.0228 (8)	0.0016 (6)	0.0084 (6)	−0.0001 (6)
C3	0.0257 (8)	0.0250 (8)	0.0287 (9)	0.0008 (6)	0.0056 (7)	−0.0005 (6)
C4	0.0213 (7)	0.0262 (8)	0.0228 (8)	−0.0009 (6)	0.0057 (6)	0.0044 (6)
C5	0.0259 (8)	0.0285 (9)	0.0250 (8)	0.0023 (6)	0.0097 (6)	−0.0002 (6)
C6	0.0281 (8)	0.0245 (8)	0.0267 (8)	0.0002 (6)	0.0099 (7)	−0.0007 (6)
C7	0.0205 (7)	0.0257 (8)	0.0239 (8)	0.0009 (6)	0.0042 (6)	0.0006 (6)
C8	0.0208 (7)	0.0254 (8)	0.0266 (8)	0.0015 (6)	0.0018 (6)	0.0022 (6)
C9	0.0250 (8)	0.0292 (9)	0.0263 (8)	0.0008 (6)	0.0051 (6)	0.0037 (7)
C10	0.0278 (8)	0.0320 (9)	0.0287 (9)	−0.0021 (7)	0.0032 (7)	0.0051 (7)
C11	0.0352 (9)	0.0275 (9)	0.0342 (9)	−0.0054 (7)	0.0027 (7)	0.0030 (7)
C12	0.0344 (9)	0.0250 (8)	0.0315 (9)	−0.0005 (7)	0.0029 (7)	−0.0035 (7)
C13	0.0286 (8)	0.0279 (8)	0.0257 (8)	−0.0018 (7)	0.0048 (7)	0.0011 (7)

Geometric parameters (Å, º)

F1—C12	1.366 (2)	C3—H3	0.9500
O1—N1	1.2392 (18)	C4—C5	1.380 (2)
O2—N1	1.235 (2)	C5—C6	1.381 (2)
O3—C7	1.2209 (19)	C5—H5	0.9500
N1—C4	1.441 (2)	C6—H6	0.9500
N2—C7	1.384 (2)	C8—C9	1.393 (2)
N2—C1	1.389 (2)	C8—C13	1.399 (2)
N2—H2A	0.907 (9)	C9—C10	1.387 (2)
N3—C7	1.376 (2)	C9—H9	0.9500
N3—C8	1.413 (2)	C10—C11	1.384 (2)
N3—H3A	0.897 (9)	C10—H10	0.9500
C1—C2	1.405 (2)	C11—C12	1.376 (3)
C1—C6	1.407 (2)	C11—H11	0.9500
C2—C3	1.372 (2)	C12—C13	1.380 (2)
C2—H2	0.9500	C13—H13	0.9500
C3—C4	1.397 (2)
O2—N1—O1	122.33 (14)	C5—C6—C1	118.87 (16)
O2—N1—C4	119.72 (14)	C5—C6—H6	120.6
O1—N1—C4	117.95 (14)	C1—C6—H6	120.6
C7—N2—C1	128.07 (14)	O3—C7—N3	124.54 (16)
C7—N2—H2A	115.5 (12)	O3—C7—N2	124.28 (15)
C1—N2—H2A	116.4 (12)	N3—C7—N2	111.18 (14)
C7—N3—C8	127.73 (14)	C9—C8—C13	119.58 (15)
C7—N3—H3A	116.9 (14)	C9—C8—N3	116.97 (15)
C8—N3—H3A	115.1 (14)	C13—C8—N3	123.46 (15)
N2—C1—C2	117.18 (14)	C10—C9—C8	120.35 (16)
N2—C1—C6	123.33 (15)	C10—C9—H9	119.8
C2—C1—C6	119.47 (15)	C8—C9—H9	119.8
C3—C2—C1	121.41 (15)	C11—C10—C9	121.22 (16)
C3—C2—H2	119.3	C11—C10—H10	119.4
C1—C2—H2	119.3	C9—C10—H10	119.4
C2—C3—C4	118.09 (15)	C12—C11—C10	116.83 (16)
C2—C3—H3	121.0	C12—C11—H11	121.6
C4—C3—H3	121.0	C10—C11—H11	121.6
C5—C4—C3	121.57 (15)	F1—C12—C11	118.40 (15)
C5—C4—N1	118.89 (14)	F1—C12—C13	117.07 (15)
C3—C4—N1	119.51 (15)	C11—C12—C13	124.52 (16)
C4—C5—C6	120.54 (15)	C12—C13—C8	117.49 (16)
C4—C5—H5	119.7	C12—C13—H13	121.3
C6—C5—H5	119.7	C8—C13—H13	121.3
C7—N2—C1—C2	168.79 (15)	C8—N3—C7—O3	4.1 (3)
C7—N2—C1—C6	−13.1 (2)	C8—N3—C7—N2	−176.20 (14)
N2—C1—C2—C3	−179.65 (14)	C1—N2—C7—O3	0.8 (3)
C6—C1—C2—C3	2.2 (2)	C1—N2—C7—N3	−178.89 (14)
C1—C2—C3—C4	−0.3 (2)	C7—N3—C8—C9	−179.05 (15)
C2—C3—C4—C5	−1.5 (2)	C7—N3—C8—C13	1.1 (3)
C2—C3—C4—N1	176.62 (13)	C13—C8—C9—C10	0.8 (2)
O2—N1—C4—C5	−176.89 (14)	N3—C8—C9—C10	−179.09 (14)
O1—N1—C4—C5	3.6 (2)	C8—C9—C10—C11	−0.2 (2)
O2—N1—C4—C3	4.9 (2)	C9—C10—C11—C12	0.0 (2)
O1—N1—C4—C3	−174.56 (13)	C10—C11—C12—F1	−179.98 (14)
C3—C4—C5—C6	1.5 (2)	C10—C11—C12—C13	−0.3 (3)
N1—C4—C5—C6	−176.63 (14)	F1—C12—C13—C8	−179.49 (14)
C4—C5—C6—C1	0.4 (2)	C11—C12—C13—C8	0.8 (3)
N2—C1—C6—C5	179.79 (14)	C9—C8—C13—C12	−1.0 (2)
C2—C1—C6—C5	−2.1 (2)	N3—C8—C13—C12	178.82 (15)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···O1i	0.91 (1)	1.99 (1)	2.890 (2)	170 (2)
N3—H3A···O2i	0.90 (1)	2.28 (1)	3.157 (2)	168 (2)

Symmetry code: (i) x+1/2, −y+1/2, z−1/2.