N-(2,5-Dimeth­oxy­phen­yl)-N′-[4-(2-hy­droxy­eth­yl)phen­yl]urea

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

doi:10.1107/S1600536810033520

. 2010 Aug 25;66(Pt 9):o2388–o2389. doi: 10.1107/S1600536810033520

N-(2,5-Dimethoxyphenyl)-N′-[4-(2-hydroxyethyl)phenyl]urea

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

PMCID: PMC3007839 PMID: 21588724

Abstract

In the title compound, C₁₇H₂₀N₂O₄, the 2,5-dimethoxyphenyl unit is essentially planar, with an r.m.s. deviation of 0.015 Å. The dihedral angle between the benzene rings is 43.66 (4)°. 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 melanin synthesis, melanogenesis and tyrosinase, see: Francisco et al. (2006 ▶); Hearing & Jimenez (1987 ▶); Prota (1988 ▶); Grimes et al. (2006 ▶); Maeda & Fukuda (1991 ▶). For the development of potent inhibitory agents of tyrosinase and melanin formation as whitening agents, see: Ohguchi et al. (2003 ▶); Lemic-Stojcevic et al. (1995 ▶); Battaini et al. (2000 ▶); Cabanes et al. (1994 ▶); Liangli (2003 ▶); Thanigaimalai et al. (2010 ▶); Hong et al. (2008 ▶); Lee et al. (2007 ▶); Yi et al. (2009 ▶, 2010 ▶); Kwak et al. (2010 ▶); Choi et al. (2010 ▶); Germanas et al. (2007 ▶); Briganti et al. (2003 ▶).

Experimental

Crystal data

C₁₇H₂₀N₂O₄
M _r = 316.35
Monoclinic,
a = 18.7551 (18) Å
b = 6.8095 (6) Å
c = 12.6881 (12) Å
β = 98.930 (3)°
V = 1600.8 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 296 K
0.31 × 0.28 × 0.08 mm

Data collection

Bruker SMART CCD area-detector diffractometer
13398 measured reflections
3563 independent reflections
2473 reflections with I > 2σ(I)
R _int = 0.045

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.108
S = 1.03
3563 reflections
222 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.15 e Å⁻³
Δρ_min = −0.16 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/S1600536810033520/vm2041sup1.cif

e-66-o2388-sup1.cif^{(16.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810033520/vm2041Isup2.hkl

e-66-o2388-Isup2.hkl^{(171.2KB, 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	0.865 (15)	2.227 (14)	2.6113 (16)	106.7 (11)
O19—H19⋯O9ⁱ	0.867 (18)	1.841 (19)	2.7080 (14)	178.0 (17)
N10—H10⋯O19ⁱⁱ	0.867 (14)	2.161 (14)	2.9799 (15)	157.4 (12)
N7—H7⋯O19ⁱⁱ	0.865 (15)	2.189 (15)	2.9837 (15)	152.6 (13)

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

Acknowledgments

This work is the result of a study on 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

Melanin synthesis is the major source of skin color and plays an important role in protection against ultraviolet rays from the sun (Francisco et al., 2006). Melanogenesis is initiated with the first step of tyrosine oxidation to dopaquinone catalyzed by tyrosinase (Hearing & Jimenez, 1987). Tyrosinase known as a polyphenol oxidase (PPO), is a multifunctional copper-containing enzyme widely distributed in nature, including bacteria, fungi, higher plants and animals (Prota, 1988). However, overproduction of melanin posed not only an esthetic problem but also a dermatological issue (Grimes et al., 2006). Therefore, tyrosinase inhibitors have become increasingly important for medicinal, food and cosmetic products that may be used to prevent or treat pigmentation disorders (Maeda & Fukuda, 1991). In this regard, diverse tyrosinase inhibitors have been actively discovered such as hydroxystilbene compounds like resveratrol (Ohguchi et al., 2003), azelaic acid (Lemic-Stojcevic et al., 1995), kojic acid (Battaini et al., 2000), albutin (Cabanes et al., 1994), (R)-HTCCA (Liangli, 2003) and N-phenylthiourea (Thanigaimalai et al., 2010). They contain aromatic, methoxy, hydroxyl (Hong et al., 2008; Lee et al., 2007), aldehyde (Yi et al., 2010), amide (Kwak et al., 2010; Choi et al., 2010), thiosemicarbazone (Yi et al., 2009) and thiazole (Germanas et al., 2007) groups in their structure, and act as a specific functional group to make the skin whiter by inhibiting the production of melanin. Although numerous compounds have been reported as skin whitening depigmenting agents, most of them have been utilized for the treatment of hyperpigmentation disorders, but none are completely satisfactory owing to adverse effects such as toxicity and/or safety concerns (Briganti et al., 2003). In our continuing search for tyrosinase inhibitors, we have synthesized the title compound, (I), from the reaction of 4-aminophenethyl alcohol and 2,5-dimethoxyphenyl isocyanate under ambient condition. Here, the crystal structure of (I) is described (Fig.1).

The 2,5-dimethoxyphenyl moiety is essentially planar, with r.m.s. deviation of 0.015 Å from the corresponding least-squares plane defined by the eleven constituent atoms. The dihedral angle between the benzene rings is 43.66 (4) °. 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).

Experimental

4-aminophenethyl alcohol 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 were used without further purification. The title compound (I) was prepared from the reaction of 4-aminophenethyl alcohol (0.18 g, 1.2 mmol) with 2,5-dimethoxyphenyl isocyanate (0.2 g, 1 mmol) in acetonitrile (6 ml). The reaction was completed within 30 min at room temperature. The reaction mixture was filtered, the solids collected and washed with dried hexane. Removal of the solvent gave a white solid (90%, m.p. 427 K). Single crystals were obtained by slow evaporation in ethanol at room temperature.