PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of actaeInternational Union of Crystallographysearchopen accessarticle submissionjournal home pagethis article
 
Acta Crystallogr Sect E Struct Rep Online. 2010 September 1; 66(Pt 9): o2388–o2389.
Published online 2010 August 25. doi:  10.1107/S1600536810033520
PMCID: PMC3007839

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

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 [triangle]); Hearing & Jimenez (1987 [triangle]); Prota (1988 [triangle]); Grimes et al. (2006 [triangle]); Maeda & Fukuda (1991 [triangle]). For the development of potent inhibitory agents of tyrosinase and melanin formation as whitening agents, see: Ohguchi et al. (2003 [triangle]); Lemic-Stojcevic et al. (1995 [triangle]); Battaini et al. (2000 [triangle]); Cabanes et al. (1994 [triangle]); Liangli (2003 [triangle]); Thanigaimalai et al. (2010 [triangle]); Hong et al. (2008 [triangle]); Lee et al. (2007 [triangle]); Yi et al. (2009 [triangle], 2010 [triangle]); Kwak et al. (2010 [triangle]); Choi et al. (2010 [triangle]); Germanas et al. (2007 [triangle]); Briganti et al. (2003 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o2388-scheme1.jpg

Experimental

Crystal data

  • C17H20N2O4
  • M r = 316.35
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o2388-efi1.jpg
  • 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
  • Δρmax = 0.15 e Å−3
  • Δρmin = −0.16 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: 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/S1600536810033520/vm2041sup1.cif

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

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

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.

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 (I), 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

C17H20N2O4F(000) = 672
Mr = 316.35Dx = 1.313 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 4670 reflections
a = 18.7551 (18) Åθ = 2.9–28.0°
b = 6.8095 (6) ŵ = 0.09 mm1
c = 12.6881 (12) ÅT = 296 K
β = 98.930 (3)°Plate, colourless
V = 1600.8 (3) Å30.31 × 0.28 × 0.08 mm
Z = 4

Data collection

Bruker SMART CCD area-detector diffractometerRint = 0.045
[var phi] and ω scansθmax = 27.5°, θmin = 2.2°
13398 measured reflectionsh = −20→24
3563 independent reflectionsk = −8→5
2473 reflections with I > 2σ(I)l = −16→7

Refinement

Refinement on F20 restraints
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.038w = 1/[σ2(Fo2) + (0.0527P)2 + 0.087P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.108(Δ/σ)max < 0.001
S = 1.03Δρmax = 0.15 e Å3
3563 reflectionsΔρmin = −0.16 e Å3
222 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
C10.81571 (7)0.4546 (2)0.70224 (10)0.0478 (3)
C20.85245 (8)0.6263 (2)0.68225 (10)0.0512 (3)
C30.91672 (8)0.6722 (2)0.74533 (12)0.0594 (4)
H30.94150.78520.73150.071*
C40.94471 (8)0.5516 (2)0.82909 (12)0.0603 (4)
H40.98770.58480.87230.072*
C50.90884 (8)0.3820 (2)0.84865 (11)0.0533 (3)
C60.84471 (8)0.3320 (2)0.78530 (11)0.0515 (3)
H60.82110.21660.79830.062*
N70.75121 (7)0.41428 (19)0.63308 (9)0.0557 (3)
H70.7438 (8)0.482 (2)0.5747 (12)0.061 (4)*
C80.69226 (7)0.31819 (18)0.65892 (10)0.0456 (3)
O90.69222 (6)0.23814 (17)0.74516 (8)0.0696 (3)
N100.63478 (6)0.32245 (17)0.58002 (9)0.0483 (3)
H100.6403 (7)0.3846 (19)0.5222 (11)0.049 (4)*
C110.56284 (7)0.26392 (17)0.58430 (10)0.0420 (3)
C120.51483 (8)0.26886 (18)0.48941 (10)0.0461 (3)
H120.53140.30140.42630.055*
C130.44293 (8)0.22611 (18)0.48762 (11)0.0475 (3)
H130.41180.22950.4230.057*
C140.41582 (7)0.17787 (17)0.58034 (11)0.0460 (3)
C150.46477 (8)0.1691 (2)0.67378 (11)0.0542 (4)
H150.44830.1340.73660.065*
C160.53723 (8)0.2105 (2)0.67713 (10)0.0519 (3)
H160.56870.20260.74130.062*
C170.33652 (8)0.1382 (2)0.57897 (12)0.0567 (4)
H17A0.33090.00880.60860.068*
H17B0.31240.13730.50560.068*
C180.30012 (9)0.2874 (2)0.64108 (12)0.0585 (4)
H18A0.25030.24940.64160.07*
H18B0.32450.29210.71430.07*
O190.30252 (6)0.47658 (15)0.59305 (8)0.0582 (3)
H190.3042 (9)0.563 (3)0.6438 (15)0.085 (6)*
O200.81964 (6)0.73557 (16)0.59742 (9)0.0684 (3)
C210.85404 (10)0.9101 (3)0.57235 (14)0.0816 (5)
H21A0.85960.99670.63280.122*
H21B0.82530.97310.51270.122*
H21C0.90070.87920.55450.122*
O220.94077 (6)0.27125 (18)0.93408 (9)0.0717 (3)
C230.90471 (10)0.1000 (3)0.96033 (14)0.0786 (5)
H23A0.85690.13360.97250.118*
H23B0.9310.04221.02370.118*
H23C0.90170.00770.90260.118*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0455 (8)0.0566 (8)0.0415 (7)−0.0014 (6)0.0072 (6)−0.0008 (6)
C20.0520 (9)0.0562 (8)0.0455 (7)−0.0027 (7)0.0075 (7)0.0017 (6)
C30.0537 (9)0.0628 (9)0.0619 (9)−0.0110 (7)0.0099 (8)−0.0016 (7)
C40.0474 (9)0.0749 (10)0.0567 (9)−0.0025 (7)0.0017 (7)−0.0022 (8)
C50.0476 (8)0.0672 (9)0.0445 (7)0.0075 (7)0.0051 (6)0.0014 (7)
C60.0512 (9)0.0565 (8)0.0468 (7)−0.0010 (6)0.0073 (7)0.0019 (6)
N70.0557 (8)0.0655 (8)0.0434 (6)−0.0115 (6)−0.0001 (6)0.0129 (6)
C80.0517 (8)0.0435 (7)0.0408 (7)0.0000 (6)0.0049 (6)0.0041 (5)
O90.0631 (7)0.0879 (8)0.0550 (6)−0.0102 (5)0.0000 (5)0.0303 (6)
N100.0527 (7)0.0535 (6)0.0381 (6)−0.0037 (5)0.0048 (5)0.0070 (5)
C110.0501 (8)0.0355 (6)0.0400 (6)0.0001 (5)0.0053 (6)−0.0010 (5)
C120.0579 (9)0.0431 (7)0.0368 (6)0.0010 (6)0.0062 (6)0.0032 (5)
C130.0566 (9)0.0420 (6)0.0409 (7)0.0016 (6)−0.0017 (6)−0.0002 (5)
C140.0530 (8)0.0362 (6)0.0482 (7)−0.0004 (6)0.0057 (6)−0.0019 (5)
C150.0608 (10)0.0614 (8)0.0416 (7)−0.0048 (7)0.0118 (7)0.0031 (6)
C160.0558 (9)0.0613 (8)0.0369 (7)−0.0025 (7)0.0012 (6)0.0023 (6)
C170.0572 (9)0.0500 (7)0.0623 (9)−0.0067 (7)0.0070 (7)0.0022 (7)
C180.0607 (10)0.0674 (9)0.0497 (8)−0.0025 (7)0.0154 (7)0.0092 (7)
O190.0772 (7)0.0569 (6)0.0417 (5)0.0039 (5)0.0133 (5)−0.0018 (5)
O200.0651 (7)0.0690 (7)0.0666 (7)−0.0169 (5)−0.0045 (6)0.0212 (5)
C210.0899 (13)0.0691 (10)0.0816 (12)−0.0219 (9)0.0003 (10)0.0213 (9)
O220.0582 (7)0.0874 (8)0.0647 (7)0.0025 (6)−0.0060 (5)0.0186 (6)
C230.0776 (12)0.0815 (12)0.0741 (11)0.0069 (9)0.0035 (9)0.0232 (10)

Geometric parameters (Å, °)

C1—C61.3875 (19)C13—C141.3913 (18)
C1—C21.4000 (19)C13—H130.93
C1—N71.4069 (18)C14—C151.3835 (19)
C2—O201.3731 (17)C14—C171.5090 (19)
C2—C31.375 (2)C15—C161.382 (2)
C3—C41.381 (2)C15—H150.93
C3—H30.93C16—H160.93
C4—C51.378 (2)C17—C181.512 (2)
C4—H40.93C17—H17A0.97
C5—O221.3787 (17)C17—H17B0.97
C5—C61.381 (2)C18—O191.4286 (17)
C6—H60.93C18—H18A0.97
N7—C81.3677 (17)C18—H18B0.97
N7—H70.865 (15)O19—H190.867 (18)
C8—O91.2226 (15)O20—C211.4122 (18)
C8—N101.3528 (17)C21—H21A0.96
N10—C111.4159 (17)C21—H21B0.96
N10—H100.867 (14)C21—H21C0.96
C11—C121.3874 (19)O22—C231.414 (2)
C11—C161.3878 (18)C23—H23A0.96
C12—C131.3764 (19)C23—H23B0.96
C12—H120.93C23—H23C0.96
C6—C1—C2119.60 (13)C15—C14—C13116.99 (13)
C6—C1—N7123.65 (13)C15—C14—C17121.59 (12)
C2—C1—N7116.72 (12)C13—C14—C17121.42 (13)
O20—C2—C3125.36 (13)C16—C15—C14122.41 (12)
O20—C2—C1114.92 (12)C16—C15—H15118.8
C3—C2—C1119.72 (13)C14—C15—H15118.8
C2—C3—C4120.47 (14)C15—C16—C11119.71 (13)
C2—C3—H3119.8C15—C16—H16120.1
C4—C3—H3119.8C11—C16—H16120.1
C5—C4—C3119.93 (14)C14—C17—C18113.43 (12)
C5—C4—H4120C14—C17—H17A108.9
C3—C4—H4120C18—C17—H17A108.9
C4—C5—O22115.81 (13)C14—C17—H17B108.9
C4—C5—C6120.46 (14)C18—C17—H17B108.9
O22—C5—C6123.73 (14)H17A—C17—H17B107.7
C5—C6—C1119.80 (13)O19—C18—C17109.69 (11)
C5—C6—H6120.1O19—C18—H18A109.7
C1—C6—H6120.1C17—C18—H18A109.7
C8—N7—C1126.35 (11)O19—C18—H18B109.7
C8—N7—H7115.6 (10)C17—C18—H18B109.7
C1—N7—H7116.0 (10)H18A—C18—H18B108.2
O9—C8—N10124.10 (13)C18—O19—H19107.0 (12)
O9—C8—N7122.73 (13)C2—O20—C21117.91 (12)
N10—C8—N7113.16 (11)O20—C21—H21A109.5
C8—N10—C11128.33 (11)O20—C21—H21B109.5
C8—N10—H10116.8 (9)H21A—C21—H21B109.5
C11—N10—H10114.2 (9)O20—C21—H21C109.5
C12—C11—C16118.65 (12)H21A—C21—H21C109.5
C12—C11—N10116.99 (11)H21B—C21—H21C109.5
C16—C11—N10124.31 (12)C5—O22—C23118.12 (12)
C13—C12—C11120.76 (12)O22—C23—H23A109.5
C13—C12—H12119.6O22—C23—H23B109.5
C11—C12—H12119.6H23A—C23—H23B109.5
C12—C13—C14121.44 (13)O22—C23—H23C109.5
C12—C13—H13119.3H23A—C23—H23C109.5
C14—C13—H13119.3H23B—C23—H23C109.5

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N7—H7···O200.865 (15)2.227 (14)2.6113 (16)106.7 (11)
O19—H19···O9i0.867 (18)1.841 (19)2.7080 (14)178.0 (17)
N10—H10···O19ii0.867 (14)2.161 (14)2.9799 (15)157.4 (12)
N7—H7···O19ii0.865 (15)2.189 (15)2.9837 (15)152.6 (13)

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: VM2041).

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.
  • Briganti, S., Camera, E. & Picardo, M. (2003). Pigm. Cell Res.16, 101–110. [PubMed]
  • Bruker (2002). 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., Lee, T., Han, B. H., Kang, S. K. & Sung, C. K. (2010). Acta Cryst. E66, o2088–o2089. [PMC free article] [PubMed]
  • Farrugia, L. J. (1999). J. Appl. Cryst.32, 837–838.
  • Francisco, S., Stefania, B., Mauro, P. & Ghanem, G. (2006). Pigm. 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]
  • Grimes, P., Nordlund, J. J., Pandya, A. G., Taylor, S., Rendon, M. & Ortonne, J. P. (2006). J. Am. Acad. Dermatol.54, 255–261. [PubMed]
  • Hearing, V. J. & Jimenez, M. (1987). Int. J. Biochem.19, 1141–1147. [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]
  • 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]
  • Maeda, K. & Fukuda, M. (1991). J. Soc. Cosmet. Chem.42, 361–368.
  • Ohguchi, K., Tanaka, T., Ito, T., Iinuma, M., Matsumoto, K., Akao, Y. & Nozawa, Y. (2003). Biosci. Biotechnol. Biochem.67, 1587–1589. [PubMed]
  • Prota, G. (1988). Med. Res. Rev.8, 525–556. [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]
  • Yi, W., Cao, R., 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. C. (2010). Eur. J. Med. Chem.45, 639–646. [PubMed]

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography