1-(3-Chloro­benz­yloxy)urea

Xi Mai; Hong-Ying Xia; Yu-Sheng Cao; Wei Tong; Guo-Gang Tu

doi:10.1107/S160053680904553X

. 2009 Nov 4;65(Pt 12):o2983. doi: 10.1107/S160053680904553X

1-(3-Chlorobenzyloxy)urea

Xi Mai ^a,^b, Hong-Ying Xia ^c, Yu-Sheng Cao ^a,^d,^*, Wei Tong ^b, Guo-Gang Tu ^b

PMCID: PMC2972183 PMID: 21578723

Abstract

The asymmetric unit of the crystal structure of the title compound, C₈H₉ClN₂O₂, contains four independent molecules. The dihedral angles between the urea N—(C=O)—N planes and the benzene rings are 83.3 (3), 87.8 (1), 89.1 (1) and 17.5 (2)° in the four molecules. Extensive N—H⋯O hydrogen bonding is present in the crystal structure.

Related literature

For general background to the design and synthesis of hydroxyurea derivatives and their in vitro antitumor activity, see: Mai et al. (2009 ▶). For related structures, see: Armagan et al. (1976 ▶); Nielsen et al. (1993 ▶); Berman & Kim (1967 ▶); Howard et al. (1967 ▶); Larsen & Jerslev (1966 ▶); Thiessen et al. (1978 ▶); Yoshitaka et al. (1993 ▶). graphic file with name e-65-o2983-scheme1.jpg

Experimental

Crystal data

C₈H₉ClN₂O₂
M _r = 200.62
Triclinic,
a = 10.830 (1) Å
b = 13.9410 (14) Å
c = 14.2750 (15) Å
α = 69.672 (1)°
β = 75.828 (2)°
γ = 70.388 (1)°
V = 1883.6 (3) Å³
Z = 8
Mo Kα radiation
μ = 0.37 mm⁻¹
T = 298 K
0.43 × 0.40 × 0.05 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.856, T _max = 0.982
9908 measured reflections
6533 independent reflections
3124 reflections with I > 2σ(I)
R _int = 0.029

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.094
S = 1.01
6533 reflections
469 parameters
H-atom parameters constrained
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.24 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: SAINT (Bruker, 2004 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S160053680904553X/xu2661sup1.cif

e-65-o2983-sup1.cif^{(28.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053680904553X/xu2661Isup2.hkl

e-65-o2983-Isup2.hkl^{(319.7KB, hkl)}

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
N1—H1⋯O5ⁱ	0.90	2.20	3.096 (3)	173
N2—H2A⋯O1ⁱ	0.86	2.16	3.023 (3)	177
N2—H2B⋯O3ⁱⁱ	0.86	2.29	2.971 (3)	136
N4—H4A⋯O7ⁱⁱⁱ	0.86	2.11	2.971 (3)	176
N4—H4B⋯O5	0.86	2.39	3.017 (3)	130
N5—H5⋯O1ⁱ	0.90	2.19	3.090 (3)	176
N6—H6A⋯O5^iv	0.86	2.07	2.925 (3)	177
N7—H7⋯O7^v	0.90	2.04	2.937 (3)	171
N8—H8A⋯O3ⁱⁱ	0.86	2.09	2.947 (3)	177
N8—H8B⋯O1ⁱ	0.86	2.25	2.976 (3)	142

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) .

Acknowledgments

The authors gratefully acknowledge the financial support of this study by the National Key S&T Special Project of China: Grand New Drug R&D (NO. 2009ZX09103–087) and the program of the Nanchang Department of Science and Technology, China (No. 2008368).

supplementary crystallographic information

Comment

Hydroxyurea (HU) is a substance used in cancer chemotherapy for many years, but it has several disadvantages, such as short half-life, extremely polar nature, the rapid development of resistance and so on. To obtain more potent compound, we have designed and synthesized HU derivatives, and evaluated their in vitro antitumor activities in our previous work (Mai et al., 2009). Here we report the crystal structure of the title compound, 3-chlorobenzyloxyurea.

The structure of 3-chlorobenzyloxyurea is shown in Fig. 1. The conformations of the N–O and C=O bonds are opposite to each other, similar to that observed in N-hydroxyurea (Howard et al., 1967; Thiessen et al., 1978; Armagan et al., 1976; Berman et al., 1967; Larsen & Jerslev, 1966), 1-hydroxy-1-methylurea, 1-hydroxy-3-methylurea (Nielsen et al., 1993), N-(6-phenoxy-2H-chromen-3-ylmethyl)-N-hydroxyurea (Yoshitaka et al., 1993) and 1-(2-fluorobenzyl)-1-(2-fluorobenzyloxy) urea (Mai et al., 2009). The bond parameters are similar to 1-(2-fluorobenzyl)-1-(2-fluorobenzyloxy)urea (Mai et al., 2009). The asymmetric unit of the title compound contains four independent molecules. The dihedral angles between the urea N-(C=O)–N planes and benzene ring are 83.3 (3)°, 87.8 (1)°, 89.1 (1)° and 17.5 (2)° for the four molecules. The N–O bonds are twisted out of the urea N–(C=O)–N planes by 18.4 (3)°, 17.9 (3)°, 19.2 (4)° and -17.8 (3)°, respectively in the four molecules. In the crystal structure, molecules are linked through intermolecular N–H···O hydrogen bonds, forming the zigzig chain.

Experimental

The title compound was synthesized by hydroxyurea (0.026 mol) with 3-chlorobenzyl chloride (0.034 mol) in methanol (80 ml) in the presence of potassium hydroxide (0.034 mol). After refluxing for 13 h, solvent was removed under reduced pressure at 308 K. The resulting crude solid was filtered and washed in trichloromethane, then recrystallized in acetone and trichloromethane solution (5:2), filtered and dried. Colorless platelet single crystals of the title compound were recrystallized from the mixed solvent acetone and n-hexane (5:10).