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 November 1; 66(Pt 11): o2705–o2706.
Published online 2010 October 2. doi:  10.1107/S1600536810038535
PMCID: PMC3009132

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

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

An external file that holds a picture, illustration, etc.
Object name is e-66-o2705-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-o2705-efi1.jpg
  • 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
  • Δρmax = 0.32 e Å−3
  • Δρmin = −0.46 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/S1600536810038535/jh2214sup1.cif

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

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

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.

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 (dashed lines).

Crystal data

C17H20N2O4F(000) = 672
Mr = 316.35Dx = 1.265 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 5519 reflections
a = 10.7275 (6) Åθ = 2.5–27.8°
b = 9.6016 (5) ŵ = 0.09 mm1
c = 16.9388 (10) ÅT = 296 K
β = 107.838 (2)°Needle, colourless
V = 1660.84 (16) Å30.31 × 0.27 × 0.13 mm
Z = 4

Data collection

Bruker SMART CCD area-detector diffractometerRint = 0.044
[var phi] and ω scansθmax = 26.0°, θmin = 2.0°
13358 measured reflectionsh = −13→6
3184 independent reflectionsk = −11→9
2296 reflections with I > 2σ(I)l = −20→16

Refinement

Refinement on F20 restraints
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.059w = 1/[σ2(Fo2) + (0.0966P)2 + 0.4089P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.186(Δ/σ)max < 0.001
S = 1.06Δρmax = 0.32 e Å3
3184 reflectionsΔρmin = −0.46 e Å3
218 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
C10.3898 (2)0.5854 (2)0.12845 (14)0.0581 (5)
C20.5212 (2)0.6136 (3)0.13837 (16)0.0698 (7)
C30.5565 (3)0.6644 (3)0.0720 (2)0.0856 (8)
H30.6440.68350.07830.103*
C40.4643 (3)0.6869 (3)−0.00277 (19)0.0845 (8)
H40.48960.7201−0.04710.101*
C50.3347 (3)0.6610 (3)−0.01298 (15)0.0724 (7)
C60.2967 (2)0.6085 (2)0.05238 (14)0.0636 (6)
H60.2090.5890.04520.076*
N70.35963 (18)0.5297 (2)0.19699 (12)0.0639 (5)
H70.423 (3)0.498 (3)0.2325 (16)0.068 (7)*
C80.24229 (19)0.5317 (2)0.21258 (12)0.0540 (5)
O90.14248 (14)0.58188 (19)0.16417 (9)0.0701 (5)
N100.24242 (19)0.4718 (2)0.28412 (11)0.0638 (5)
H100.315 (3)0.441 (3)0.3168 (16)0.075 (8)*
C110.1271 (2)0.4629 (3)0.31035 (13)0.0683 (7)
H11A0.13420.38140.34530.082*
H11B0.05140.45010.26180.082*
C120.1046 (2)0.5896 (3)0.35756 (13)0.0684 (7)
H12A0.09490.67060.3220.082*
H12B0.02310.57740.37030.082*
C130.21277 (19)0.6172 (2)0.43716 (13)0.0558 (5)
C140.2326 (3)0.5296 (3)0.50382 (15)0.0820 (8)
H140.17920.45190.49920.098*
C150.3299 (3)0.5540 (3)0.57772 (16)0.0874 (9)
H150.34130.49260.62190.105*
C160.40944 (19)0.6679 (2)0.58626 (13)0.0597 (6)
C170.3892 (2)0.7585 (2)0.52187 (14)0.0638 (6)
H170.44040.83830.52740.077*
C180.2917 (2)0.7315 (2)0.44770 (14)0.0654 (6)
H180.27980.79350.40380.078*
O190.50449 (17)0.6876 (2)0.66089 (11)0.0816 (6)
H190.552 (3)0.759 (4)0.658 (2)0.122*
O200.60539 (16)0.5880 (3)0.21599 (12)0.0954 (7)
C210.7414 (3)0.6140 (7)0.2294 (2)0.1518 (19)
H21A0.78980.59140.28570.228*
H21B0.75410.71050.21920.228*
H21C0.77190.55740.19230.228*
O220.2495 (2)0.6902 (3)−0.08960 (12)0.0991 (7)
C230.1155 (4)0.6852 (3)−0.10046 (19)0.1056 (11)
H23A0.06810.7078−0.15690.158*
H23B0.0940.7512−0.0640.158*
H23C0.09190.5933−0.08790.158*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0566 (11)0.0614 (13)0.0551 (12)0.0002 (9)0.0154 (10)−0.0068 (10)
C20.0567 (13)0.0777 (16)0.0735 (15)−0.0004 (11)0.0175 (12)−0.0106 (12)
C30.0665 (15)0.097 (2)0.100 (2)−0.0084 (14)0.0355 (15)−0.0010 (17)
C40.0879 (18)0.0901 (19)0.0855 (19)−0.0109 (15)0.0411 (16)0.0065 (15)
C50.0828 (16)0.0724 (16)0.0603 (14)−0.0089 (12)0.0195 (12)0.0028 (11)
C60.0610 (12)0.0702 (15)0.0565 (13)−0.0088 (10)0.0135 (10)−0.0019 (11)
N70.0488 (10)0.0852 (14)0.0512 (11)0.0095 (9)0.0059 (8)0.0050 (9)
C80.0531 (11)0.0588 (12)0.0426 (10)0.0045 (9)0.0037 (9)−0.0033 (9)
O90.0538 (8)0.0941 (12)0.0551 (9)0.0151 (8)0.0057 (7)0.0144 (8)
N100.0603 (11)0.0815 (13)0.0453 (10)0.0137 (9)0.0100 (8)0.0071 (9)
C110.0644 (13)0.0858 (17)0.0483 (12)−0.0152 (11)0.0079 (10)−0.0045 (11)
C120.0465 (11)0.1008 (18)0.0511 (12)0.0057 (11)0.0050 (9)−0.0050 (12)
C130.0456 (10)0.0698 (14)0.0466 (11)0.0055 (9)0.0061 (8)−0.0026 (10)
C140.0843 (17)0.0838 (17)0.0614 (14)−0.0297 (14)−0.0020 (12)0.0050 (13)
C150.1003 (19)0.0795 (17)0.0587 (14)−0.0219 (15)−0.0109 (13)0.0176 (13)
C160.0501 (11)0.0611 (13)0.0541 (12)0.0033 (9)−0.0044 (9)0.0008 (10)
C170.0597 (12)0.0574 (12)0.0646 (13)−0.0045 (10)0.0047 (10)0.0023 (10)
C180.0679 (14)0.0651 (14)0.0544 (12)0.0060 (11)0.0056 (10)0.0120 (10)
O190.0738 (11)0.0760 (12)0.0659 (10)−0.0059 (8)−0.0214 (8)0.0041 (8)
O200.0496 (9)0.1491 (19)0.0801 (12)0.0044 (10)0.0088 (8)−0.0044 (12)
C210.0506 (16)0.283 (6)0.114 (3)−0.004 (2)0.0139 (17)−0.020 (3)
O220.0948 (14)0.1328 (18)0.0650 (11)−0.0083 (12)0.0173 (10)0.0177 (11)
C230.136 (3)0.0730.0813 (19)−0.0271 (17)−0.0063 (19)0.0146 (15)

Geometric parameters (Å, °)

C1—C61.385 (3)C12—H12A0.97
C1—C21.394 (3)C12—H12B0.97
C1—N71.403 (3)C13—C181.364 (3)
C2—O201.370 (3)C13—C141.371 (3)
C2—C31.381 (4)C14—C151.382 (3)
C3—C41.364 (4)C14—H140.93
C3—H30.93C15—C161.367 (3)
C4—C51.370 (4)C15—H150.93
C4—H40.93C16—C171.360 (3)
C5—O221.368 (3)C16—O191.373 (2)
C5—C61.387 (3)C17—C181.391 (3)
C6—H60.93C17—H170.93
N7—C81.363 (3)C18—H180.93
N7—H70.82 (3)O19—H190.86 (4)
C8—O91.230 (2)O20—C211.429 (3)
C8—N101.341 (3)C21—H21A0.96
N10—C111.440 (3)C21—H21B0.96
N10—H100.86 (3)C21—H21C0.96
C11—C121.515 (4)O22—C231.394 (4)
C11—H11A0.97C23—H23A0.96
C11—H11B0.97C23—H23B0.96
C12—C131.509 (3)C23—H23C0.96
C6—C1—C2119.7 (2)C13—C12—H12B108.7
C6—C1—N7123.2 (2)C11—C12—H12B108.7
C2—C1—N7117.1 (2)H12A—C12—H12B107.6
O20—C2—C3125.5 (2)C18—C13—C14116.88 (19)
O20—C2—C1115.2 (2)C18—C13—C12122.3 (2)
C3—C2—C1119.3 (2)C14—C13—C12120.8 (2)
C4—C3—C2120.7 (2)C13—C14—C15121.7 (2)
C4—C3—H3119.7C13—C14—H14119.1
C2—C3—H3119.7C15—C14—H14119.1
C3—C4—C5120.5 (3)C16—C15—C14120.3 (2)
C3—C4—H4119.7C16—C15—H15119.8
C5—C4—H4119.7C14—C15—H15119.8
O22—C5—C4116.1 (2)C17—C16—C15119.08 (19)
O22—C5—C6123.9 (2)C17—C16—O19122.8 (2)
C4—C5—C6120.0 (2)C15—C16—O19118.1 (2)
C1—C6—C5119.8 (2)C16—C17—C18119.7 (2)
C1—C6—H6120.1C16—C17—H17120.1
C5—C6—H6120.1C18—C17—H17120.1
C8—N7—C1127.99 (19)C13—C18—C17122.2 (2)
C8—N7—H7118.4 (18)C13—C18—H18118.9
C1—N7—H7113.4 (18)C17—C18—H18118.9
O9—C8—N10122.0 (2)C16—O19—H19110 (2)
O9—C8—N7122.9 (2)C2—O20—C21117.5 (3)
N10—C8—N7115.05 (18)O20—C21—H21A109.5
C8—N10—C11122.76 (19)O20—C21—H21B109.5
C8—N10—H10118.8 (17)H21A—C21—H21B109.5
C11—N10—H10118.4 (17)O20—C21—H21C109.5
N10—C11—C12114.0 (2)H21A—C21—H21C109.5
N10—C11—H11A108.8H21B—C21—H21C109.5
C12—C11—H11A108.8C5—O22—C23118.7 (2)
N10—C11—H11B108.8O22—C23—H23A109.5
C12—C11—H11B108.8O22—C23—H23B109.5
H11A—C11—H11B107.7H23A—C23—H23B109.5
C13—C12—C11114.19 (19)O22—C23—H23C109.5
C13—C12—H12A108.7H23A—C23—H23C109.5
C11—C12—H12A108.7H23B—C23—H23C109.5

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N7—H7···O200.82 (3)2.23 (2)2.617 (3)109 (2)
N7—H7···O19i0.82 (3)2.48 (3)3.182 (3)144 (2)
N10—H10···O19i0.86 (3)2.23 (3)3.005 (3)150 (2)
O19—H19···O9ii0.86 (4)1.80 (4)2.654 (3)172 (4)

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: JH2214).

References

  • 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]
  • Casanola-Martin, G. M., Khan, M. T. H., Marrero-Ponce, Y., Ather, A., Sultankhodzhaev, F. & Torrens, F. (2006). Bioorg. Med. Chem. Lett.16, 324–330. [PubMed]
  • Farrugia, L. J. (1999). J. Appl. Cryst.32, 837–838.
  • Garcia, A. & Fulrton, J. E. (1996). Dermatol. Surg.22, 443–447. [PubMed]
  • Khan, K. M., Maharvi, G. M., Khan, M. T. H., Shaikh, A. J., Perveen, S., Begum, S. & Choudhary, M. I. (2006). Bioorg. Med. Chem.14, 344–351. [PubMed]
  • Kojima, S., Yamaguch, K., Morita, K., Ueno, Y. & Paolo, R. (1995). Biol. Pharm. Bull.18, 1076–1080. [PubMed]
  • Kubo, I., Kinst-Hori, I., Chaudhuri, S. K., Sanchez, Y. & Ogura, T. (2000). Bioorg. Med. Chem.8, 1749–1755. [PubMed]
  • Lemic-Stojcevic, L., Nias, A. H. & Breathnach, A. S. (1995). Exp. Dermatol.4, 79–81. [PubMed]
  • Passi, S. & Nazzaro-Porro, M. (1981). Br. J. Dermatol.104, 659–665. [PubMed]
  • Perez-Gilbert, M. & Garcia-Carmona, F. (2001). Biochem. Biophys. Res. Commun.285, 257–261. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Shiino, M., Watanabe, Y. & Umezawa, K. (2001). Bioorg. Med. Chem.9, 1233–1240. [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]

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