1-(2,5-Dimethoxyphenyl)-3-(2-hydroxyethyl)urea

In the title compound, C11H16N2O4, the 2,5-dimethoxyphenyl moiety is almost planar, with an r.m.s. deviation of 0.026 Å. The dihedral angle between the benzene ring and the plane of the urea moiety is 13.86 (5)°. 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.

In the title compound, C 11 H 16 N 2 O 4 , the 2,5-dimethoxyphenyl moiety is almost planar, with an r.m.s. deviation of 0.026 Å . The dihedral angle between the benzene ring and the plane of the urea moiety is 13.86 (5) . The molecular structure is stabilized by a short intramolecular N-HÁ Á ÁO hydrogen bond. In the crystal, intermolecular N-HÁ Á ÁO and O-HÁ Á ÁO hydrogen bonds link the molecules into a three-dimensional network.
We wish to thank the DBIO company for partial support of this work.
Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: JH2184).

Comment
The melanin production is primarily responsible for the skin color, and melanin plays a vital role in the absorption of free radicals formed in cytoplasm and in protecting human skin from the harmful UV-radiation and from scavenging chemicals (Francisco et al., 2006). Tyrosinase is a multi-functional copper-containing enzyme widely distributed in microorganisms, plants and animals (Jimenez et al., 2001), and it is a key enzyme that catalyzes two distinct reactions of melanin synthesis; the hydroxylation of tyrosine by monophenolase action and the oxidation of L-dopa to o-dopaquinone by diphenolase action (Korner & Pawelek, 1982). The increased production and accumulation of melanin characterizes a large number of dermatological disorders, which include acquired hyper-pigmentation, causing melasma, freckles, post-inflammatory melanoderma, and solar lentigo (Urabe et al., 1998). Therefore, treatments using potent inhibitory agents on tyrosinase and melanin formation may be cosmetically useful. In recent years, various inhibitors were obtained from natural and synthetic sources with their industrial importance such as 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, hyroxyl (Hong et al., 2008;Lee et al., 2007), aldehyde (Yi et al., 2010), amide (Kwak 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. However, most of them are not potent enough to put into practical use due to their weak individual activities, poor skin penetration, low stability of formulations, toxicity and/or safety concerns. Consequently, much research is needed to develop novel tyrosinase inhibitors with better activities together with lower side effects. To complement the inadequacy of current whitening agents mentioned above and maximize the inhibition of melanin creation, we have synthesized the title compound, 1-(2,5-dimethoxyphenyl)-3-(2hydroxyethyl)urea, (I), from the reaction of ethanolamine and 2,5-dimethoxyphenyl isocyanate under ambient condition.
The 2,5-dimethoxyphenyl moiety is almost planar with r.m.s. deviation of 0.026 Å from the corresponding least-squares plane defined by the ten constituent atoms. The dihedral angle between the phenyl ring and the plane of urea moiety is 13.86 (5) °. The molecular structure is stabilized by a short intramolecular N7-H7···O14 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).

Experimental
The ethanolamine 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 ethanolamine (0.1 ml, 2 mmol) with 2,5-dimethoxyphenyl isocyanate (0.5 g, 3 mmol) in acetonitrile (6 ml). The reaction was completed within 10 min at room temperature.
The reaction mixture was filtered rapidly with ether. Removal of the solvent gave a white solid (90% m.p. 419 K). Single crystals were obtained by slow evaporation of the ethanol at room temperature.

supplementary materials sup-2 Refinement
The H atoms of the NH and OH groups were located in a difference Fourier map and refined freely. The remaining H atoms were positioned geometrically and refined using a riding model with C-H = 0.93-0.97 Å, and with U iso (H) = 1.2U eq (C) for aromatic and metylene, and 1.5U eq (C) for methyl H atoms. Fig. 1. Molecular structure of (l), showing the atom-numbering scheme and 50% probability ellipsoids. Intramolecular N-H···O bond is shown as dashed lines.