N-(2,5-Dimeth­oxy­phen­yl)-N′-(4-hy­droxy­pheneth­yl)urea

Hyeong Choi; Byung Hee Han; Yong Suk Shim; Sung Kwon Kang; Chang Keun Sung

doi:10.1107/S1600536810038535

. 2010 Oct 2;66(Pt 11):o2705–o2706. doi: 10.1107/S1600536810038535

N-(2,5-Dimethoxyphenyl)-N′-(4-hydroxyphenethyl)urea

Hyeong Choi ^a, Byung Hee Han ^a, Yong Suk Shim ^a, Sung Kwon Kang ^a,^*, Chang Keun Sung ^b

PMCID: PMC3009132 PMID: 21588920

Abstract

In the title compound, C₁₇H₂₀N₂O₄, the 2,5-dimethoxyphenyl unit is almost planar, with an r.m.s. deviation of 0.015 Å. The dihedral angle between the 2,5-dimethoxyphenyl ring and the urea plane is 20.95 (8)°. The H atoms of the urea NH groups are positioned syn to each other. The molecular structure is stabilized by a short intramolecular N—H⋯O hydrogen bond. In the crystal, intermolecular N—H⋯O and O—H⋯O hydrogen bonds link the molecules into a three-dimensional network.

Related literature

For general background to tyrosinase, see: Kubo et al. (2000 ▶); Perez-Gilbert & Garcia-Carmona (2001 ▶). For the development of tyrosinase inhibitors, see: Shiino et al. (2001 ▶); Khan et al. (2006 ▶); Garcia & Fulrton (1996 ▶); Kojima et al. (1995 ▶); Cabanes et al. (1994 ▶); Lemic-Stojcevic et al. 1995 ▶); Casanola-Martin et al. (2006 ▶); Thanigaimalai et al. (2010 ▶); Passi & Nazzaro-Porro (1981 ▶).

Experimental

Crystal data

C₁₇H₂₀N₂O₄
M _r = 316.35
Monoclinic,
a = 10.7275 (6) Å
b = 9.6016 (5) Å
c = 16.9388 (10) Å
β = 107.838 (2)°
V = 1660.84 (16) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 296 K
0.31 × 0.27 × 0.13 mm

Data collection

Bruker SMART CCD area-detector diffractometer
13358 measured reflections
3184 independent reflections
2296 reflections with I > 2σ(I)
R _int = 0.044

Refinement

R[F ² > 2σ(F ²)] = 0.059
wR(F ²) = 0.186
S = 1.06
3184 reflections
218 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.46 e Å⁻³

Data collection: SMART (Bruker, 2002 ▶); cell refinement: SAINT (Bruker, 2002 ▶); 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, 2010 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810038535/jh2214sup1.cif

e-66-o2705-sup1.cif^{(16.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810038535/jh2214Isup2.hkl

e-66-o2705-Isup2.hkl^{(153.1KB, 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
N7—H7⋯O20	0.82 (3)	2.23 (2)	2.617 (3)	109 (2)
N7—H7⋯O19ⁱ	0.82 (3)	2.48 (3)	3.182 (3)	144 (2)
N10—H10⋯O19ⁱ	0.86 (3)	2.23 (3)	3.005 (3)	150 (2)
O19—H19⋯O9ⁱⁱ	0.86 (4)	1.80 (4)	2.654 (3)	172 (4)

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

This work is the result of a study performed under the ‘Human Resource Development Center for Economic Region Leading Industry’ Project, supported by the Ministry of Education, Science & Technology (MEST) and the National Research Foundation of Korea (NRF).

supplementary crystallographic information

Comment

Tyrosinase known as a polyphenol oxidase, is a multifunctional copper-containing enzyme widely distributed in nature. It is the key enzyme in the undesirable browning of fruits and vegetables, and coloring of skin, hair, and eyes in animals (Kubo et al., 2000; Perez-Gilbert & Garcia-Carmona, 2001). Nowadays, tyrosinase inhibitors are thought to be clinically useful for the treatment of some dermatological disorders associated with melanin hyperpigmentation (Shiino et al., 2001) and useful in cosmetic products and food industry (Khan et al., 2006). Recently, various tyrosinase inhibitors have been reported such as hydroquinone (Garcia & Fulrton, 1996), ascorbic acid derivatives (Kojima et al., 1995), kojic acid (Cabanes et al., 1994), azelaic acid (Lemic-Stojcevic et al., 1995), arbutin (Casanola-Martin et al., 2006) and N-phenylthiourea (PTU) (Thanigaimalai et al., 2010). Most of the tyrosinase inhibitors are phenol/catechol derivatives, structurally similar to tyrosine or L-DOPA, which act as suicide substrates of tyrosinase (Passi & Nazzaro-Porro, 1981). However, most of them are not potent enough to put into practical use due to their weak individual activities or safety concerns. Undoubtedly, it is required to search and develop novel tyrosinase inhibitors with better activities together with lower side effects. In continuing our research on the development of tyrosinase inhibitors for new whitening agents, we have synthesized the title compound, (I), from the reaction of 2-(4-hydroxyphenyl)ethyl amine and 2,5-dimethoxyphenyl isocyanate under ambient condition. Here, we report the crystal structure of the title compound, (I).

The 2,5-dimethoxyphenyl moiety is almost planar with r.m.s. deviation of 0.015 Å from the corresponding least-squares plane defined by the nine constituent atoms. The dihedral angle between the phenyl ring and the plane of urea moiety is 20.95 (8) °. The molecular structure is stabilized by a short intramolecular N7—H7···O20 hydrogen bond (Fig. 1). In the crystal, intermolecular N—H···O and O—H···O hydrogen bonds link the molecules into a three-dimensional network (Fig. 2, Table 1). The H atoms of the NH groups of urea are positioned syn to each other.

Experimental

The tyramine and 2,5-dimethoxyphenyl isocyanate were purchased from Sigma Chemical Co. Solvents used for organic synthesis were redistilled before use. All other chemicals and solvents were of analytical grade and used without further purification. The title compound (I) was prepared from the reaction of 2-(4-hydroxyphenyl)ethyl amine (0.20 g, 1 mmol) with 2,5-dimethoxyphenyl isocyanate (0.18 g, 1.2 mmol) in acetonitrile (8 ml) and added 4-(dimethylamino)pyridine (0.06 g, 0.5 mmol) as a catalyst, with stirring. The reaction was completed within 5 h at room temperature. The solvents were removed under reduced pressure. The solids collected and washed with dichloromethane. Removal of the solvent gave a light yellow solid (69%, m.p. 436 K). Single crystals were obtained by slow evaporation of the ethanol at room temperature.