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Acta Crystallogr Sect E Struct Rep Online. 2010 August 1; 66(Pt 8): o2088–o2089.
Published online 2010 July 24. doi:  10.1107/S1600536810028436
PMCID: PMC3007247

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

Abstract

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.

Related literature

For general background, see: Francisco et al. (2006 [triangle]); Jimenez et al. (2001 [triangle]); Korner & Pawelek (1982 [triangle]); Urabe et al. (1998 [triangle]). For the development of potent inhibitory agents of tyrosinase and melanin formation as whitening agents, see: Battaini et al. (2000 [triangle]); Cabanes et al. (1994 [triangle]); Choi et al. (2010 [triangle]); Germanas et al. (2007 [triangle]); Hong et al. (2008 [triangle]); Kwak et al. (2010 [triangle]); Lemic-Stojcevic et al. (1995 [triangle]); Lee et al. (2007 [triangle]); Liangli (2003 [triangle]); Thanigaimalai et al. (2010 [triangle]); Yi et al. (2009 [triangle], 2010 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o2088-scheme1.jpg

Experimental

Crystal data

  • C11H16N2O4
  • M r = 240.26
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o2088-efi1.jpg
  • a = 10.8571 (9) Å
  • b = 11.5559 (10) Å
  • c = 9.9337 (8) Å
  • β = 109.514 (4)°
  • V = 1174.73 (17) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.10 mm−1
  • T = 173 K
  • 0.21 × 0.18 × 0.09 mm

Data collection

  • Bruker SMART CCD area-detector diffractometer
  • 9411 measured reflections
  • 2352 independent reflections
  • 1982 reflections with I > 2σ(I)
  • R int = 0.062

Refinement

  • R[F 2 > 2σ(F 2)] = 0.034
  • wR(F 2) = 0.090
  • S = 1.07
  • 2352 reflections
  • 168 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.19 e Å−3
  • Δρmin = −0.25 e Å−3

Data collection: SMART (Bruker, 2002 [triangle]); cell refinement: SAINT (Bruker, 2002 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 [triangle]) and DIAMOND (Brandenburg, 2010 [triangle]); software used to prepare material for publication: WinGX (Farrugia, 1999 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810028436/jh2184sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810028436/jh2184Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

We wish to thank the DBIO company for partial support of this work.

supplementary crystallographic information

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; 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. 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-(2-hydroxyethyl)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.

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 Uiso(H) = 1.2Ueq (C) for aromatic and metylene, and 1.5Ueq(C) for methyl H atoms.

Figures

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.
Fig. 2.
Part of the crystal structure of (I), showing 3-D network of molecules linked by intermolecular N—H···O and O—H···O hydrogen bonds.

Crystal data

C11H16N2O4F(000) = 512
Mr = 240.26Dx = 1.358 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 4246 reflections
a = 10.8571 (9) Åθ = 2.8–28.2°
b = 11.5559 (10) ŵ = 0.10 mm1
c = 9.9337 (8) ÅT = 173 K
β = 109.514 (4)°Block, colourless
V = 1174.73 (17) Å30.21 × 0.18 × 0.09 mm
Z = 4

Data collection

Bruker SMART CCD area-detector diffractometerRint = 0.062
[var phi] and ω scansθmax = 26.5°, θmin = 2.7°
9411 measured reflectionsh = −6→13
2352 independent reflectionsk = −14→9
1982 reflections with I > 2σ(I)l = −12→7

Refinement

Refinement on F20 restraints
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.034w = 1/[σ2(Fo2) + (0.0526P)2] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.090(Δ/σ)max < 0.001
S = 1.07Δρmax = 0.19 e Å3
2352 reflectionsΔρmin = −0.25 e Å3
168 parameters

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
C10.26322 (10)0.50237 (9)0.48181 (12)0.0208 (2)
C20.15431 (11)0.43224 (9)0.47055 (12)0.0220 (3)
C30.05312 (11)0.42372 (9)0.34222 (12)0.0252 (3)
H3−0.0190.37780.33570.03*
C40.05831 (11)0.48333 (9)0.22288 (13)0.0264 (3)
H4−0.01010.47780.13660.032*
C50.16604 (11)0.55102 (9)0.23333 (12)0.0242 (3)
C60.26888 (11)0.56150 (9)0.36195 (12)0.0228 (3)
H60.34070.60760.36770.027*
N70.36023 (9)0.50709 (8)0.61700 (10)0.0234 (2)
H70.3458 (12)0.4616 (12)0.6799 (15)0.035 (4)*
C80.45894 (10)0.58708 (9)0.66522 (12)0.0205 (2)
O90.48440 (8)0.65994 (6)0.58761 (8)0.0260 (2)
N100.52601 (9)0.57919 (8)0.80586 (11)0.0250 (2)
H100.5012 (13)0.5293 (11)0.8553 (15)0.033 (3)*
C110.62695 (11)0.66229 (10)0.87792 (12)0.0268 (3)
H11A0.58920.73910.86960.032*
H11B0.69360.66310.83290.032*
C120.68773 (11)0.63093 (10)1.03317 (13)0.0271 (3)
H12A0.73150.55681.04070.032*
H12B0.75310.68841.08010.032*
O130.59367 (8)0.62435 (7)1.10450 (9)0.0260 (2)
H130.5628 (15)0.6954 (15)1.1048 (16)0.054 (5)*
O140.15906 (8)0.37701 (6)0.59484 (9)0.0274 (2)
C150.05328 (12)0.30175 (10)0.58780 (14)0.0312 (3)
H15A−0.02650.34540.56190.047*
H15B0.06860.26620.67930.047*
H15C0.04650.24290.51750.047*
O160.16393 (8)0.60560 (7)0.10891 (9)0.0329 (2)
C170.26678 (12)0.68455 (11)0.11745 (14)0.0343 (3)
H17A0.2670.74540.18330.051*
H17B0.25390.7170.02480.051*
H17C0.34890.64450.150.051*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0197 (5)0.0189 (5)0.0216 (6)0.0014 (4)0.0039 (5)−0.0032 (4)
C20.0235 (6)0.0185 (5)0.0240 (6)0.0011 (4)0.0078 (5)−0.0006 (4)
C30.0214 (6)0.0238 (6)0.0283 (7)−0.0040 (5)0.0057 (5)−0.0044 (5)
C40.0232 (6)0.0288 (6)0.0226 (7)−0.0007 (5)0.0013 (5)−0.0040 (5)
C50.0259 (6)0.0244 (6)0.0207 (6)0.0029 (5)0.0058 (5)−0.0004 (4)
C60.0213 (6)0.0227 (5)0.0234 (6)−0.0017 (4)0.0063 (5)−0.0010 (5)
N70.0239 (5)0.0238 (5)0.0197 (5)−0.0049 (4)0.0034 (5)0.0027 (4)
C80.0192 (6)0.0200 (5)0.0215 (6)0.0012 (4)0.0058 (5)−0.0016 (4)
O90.0280 (5)0.0256 (4)0.0225 (5)−0.0062 (3)0.0061 (4)0.0023 (3)
N100.0258 (5)0.0261 (5)0.0200 (6)−0.0075 (4)0.0034 (5)0.0014 (4)
C110.0240 (6)0.0309 (6)0.0237 (7)−0.0082 (5)0.0054 (5)−0.0030 (5)
C120.0223 (6)0.0321 (6)0.0241 (7)−0.0023 (5)0.0042 (5)−0.0035 (5)
O130.0307 (5)0.0228 (4)0.0247 (5)−0.0005 (3)0.0095 (4)0.0010 (3)
O140.0259 (4)0.0278 (4)0.0264 (5)−0.0069 (3)0.0060 (4)0.0041 (3)
C150.0289 (6)0.0268 (6)0.0378 (7)−0.0076 (5)0.0111 (6)0.0028 (5)
O160.0316 (5)0.0406 (5)0.0220 (5)−0.0059 (4)0.0031 (4)0.0058 (4)
C170.0330 (7)0.0360 (7)0.0326 (7)−0.0024 (5)0.0092 (6)0.0094 (6)

Geometric parameters (Å, °)

C1—C61.3918 (15)N10—H100.856 (14)
C1—N71.4039 (15)C11—C121.5051 (16)
C1—C21.4068 (15)C11—H11A0.97
C2—O141.3754 (13)C11—H11B0.97
C2—C31.3806 (17)C12—O131.4262 (13)
C3—C41.3883 (16)C12—H12A0.97
C3—H30.93C12—H12B0.97
C4—C51.3819 (16)O13—H130.887 (17)
C4—H40.93O14—C151.4236 (13)
C5—O161.3809 (13)C15—H15A0.96
C5—C61.3931 (17)C15—H15B0.96
C6—H60.93C15—H15C0.96
N7—C81.3746 (14)O16—C171.4224 (14)
N7—H70.870 (14)C17—H17A0.96
C8—O91.2337 (12)C17—H17B0.96
C8—N101.3457 (15)C17—H17C0.96
N10—C111.4531 (14)
C6—C1—N7124.46 (10)N10—C11—C12110.24 (9)
C6—C1—C2119.40 (10)N10—C11—H11A109.6
N7—C1—C2116.14 (10)C12—C11—H11A109.6
O14—C2—C3125.13 (9)N10—C11—H11B109.6
O14—C2—C1114.68 (10)C12—C11—H11B109.6
C3—C2—C1120.19 (10)H11A—C11—H11B108.1
C2—C3—C4120.42 (10)O13—C12—C11112.35 (10)
C2—C3—H3119.8O13—C12—H12A109.1
C4—C3—H3119.8C11—C12—H12A109.1
C5—C4—C3119.44 (11)O13—C12—H12B109.1
C5—C4—H4120.3C11—C12—H12B109.1
C3—C4—H4120.3H12A—C12—H12B107.9
O16—C5—C4115.51 (10)C12—O13—H13106.6 (10)
O16—C5—C6123.35 (10)C2—O14—C15116.85 (9)
C4—C5—C6121.13 (10)O14—C15—H15A109.5
C1—C6—C5119.41 (10)O14—C15—H15B109.5
C1—C6—H6120.3H15A—C15—H15B109.5
C5—C6—H6120.3O14—C15—H15C109.5
C8—N7—C1127.44 (9)H15A—C15—H15C109.5
C8—N7—H7117.6 (9)H15B—C15—H15C109.5
C1—N7—H7114.0 (9)C5—O16—C17117.49 (9)
O9—C8—N10122.59 (10)O16—C17—H17A109.5
O9—C8—N7123.54 (10)O16—C17—H17B109.5
N10—C8—N7113.87 (9)H17A—C17—H17B109.5
C8—N10—C11121.61 (9)O16—C17—H17C109.5
C8—N10—H10118.4 (9)H17A—C17—H17C109.5
C11—N10—H10119.5 (9)H17B—C17—H17C109.5

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N7—H7···O140.870 (14)2.153 (13)2.5995 (12)111.4 (11)
N7—H7···O13i0.870 (14)2.251 (14)3.0473 (13)152.3 (12)
N10—H10···O13i0.856 (14)2.156 (14)2.9642 (12)157.1 (12)
O13—H13···O9ii0.887 (17)1.858 (18)2.7417 (11)174.0 (15)

Symmetry codes: (i) −x+1, −y+1, −z+2; (ii) x, −y+3/2, z+1/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: JH2184).

References

  • Battaini, G., Monzani, E., Casella, L., Santagostini, L. & Pagliarin, R. (2000). J. Biol. Inorg. Chem.5, 262–268. [PubMed]
  • Brandenburg, K. (2010). DIAMOND Crystal Impact GbR, Bonn, Germany.
  • Bruker (2002). SADABS, SAINT and SMART Bruker AXS Inc., Madison, Wisconsin, USA.
  • Cabanes, J., Chazarra, S. & Garcia-Carmona, F. (1994). J. Pharm. Pharmacol.46, 982–985. [PubMed]
  • Choi, H., Han, B. H., Lee, T., Kang, S. K. & Sung, C. K. (2010). Acta Cryst. E66, o1142. [PMC free article] [PubMed]
  • Farrugia, L. J. (1997). J. Appl. Cryst.30, 565.
  • Farrugia, L. J. (1999). J. Appl. Cryst.32, 837–838.
  • Francisco, S., Stefania, B., Mauro, P. & Ghanem, G. (2006). Pigment Cell Res.19, 550–571. [PubMed]
  • Germanas, J. P., Wang, S., Miner, A., Hao, W. & Ready, J. M. (2007). Bioorg. Med. Chem. Lett.17, 6871–6875. [PubMed]
  • Hong, W. K., Heo, J. Y., Han, B. H., Sung, C. K. & Kang, S. K. (2008). Acta Cryst. E64, o49. [PMC free article] [PubMed]
  • Jimenez, M., Chazarra, S., Escribano, J., Cabanes, J. & Garcia-Carmona, F. (2001). J. Agric. Food Chem.49, 4060–4063. [PubMed]
  • Korner, A. M. & Pawelek, J. M. (1982). Science, 217, 1163–1165. [PubMed]
  • Kwak, S. Y., Noh, J. M., Park, S. H., Byun, J. W. & Choi, H. R. (2010). Bioorg. Med. Chem. Lett.20, 738–742. [PubMed]
  • Lee, C. W., Son, E. M., Kim, H. S. & Xu, P. (2007). Bioorg. Med. Chem. Lett.17, 5462–5464. [PubMed]
  • Lemic-Stojcevic, L., Nias, A. H. & Breathnach, A. S. (1995). Exp. Dermatol.4, 79–81. [PubMed]
  • Liangli, Y. (2003). J. Agric. Food Chem.51, 2344–2347. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Thanigaimalai, P., Le, H. T. A., Lee, K. C., Bang, S. C., Sharma, V. K., Yun, C. Y., Roh, E., Hwang, B. Y., Kim, Y. S. & Jung, S. H. (2010). Bioorg. Med. Chem. Lett.20, 2991–2993. [PubMed]
  • Urabe, K., Nakayama, J., Hori, Y., Norlund, J. J., Biossy, R. E., Hearing, V. J., King, R. A. & Ortonne, J. P. (1998). The Pigmentary System: Physiology and Pathophysiology, pp. 909–991. New York: Oxford University Press Inc.
  • Yi, W., Cao, R. H., Chen, Z. Y. Yu. L. Ma. L. & Song, H. C. (2009). Chem. Pharm. Bull.7, 1273–1277. [PubMed]
  • Yi, W., Cao, R., Peng, W., Wen, H., Yan, Q., Zhou, B., Ma, L. & Song, H. (2010). Eur. J. Med. Chem.45, 639–646. [PubMed]

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