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Acta Crystallogr Sect E Struct Rep Online. 2010 December 1; 66(Pt 12): o3303–o3304.
Published online 2010 November 27. doi:  10.1107/S160053681004866X
PMCID: PMC3011736

1-(4-Hy­droxy­phen­yl)-3-(3,4,5-tri­methoxy­phen­yl)thio­urea

Abstract

In the title compound, C16H18N2O4S, the dihedral angle between the hy­droxy­phenyl ring and the plane of the thio­urea moiety is 54.53 (8)°. The H atoms of the NH groups of thio­urea are positioned anti to each other. In the crystal, inter­molecular N—H(...)S, N—H(...)O, and O—H(...)S hydrogen bonds link the mol­ecules into a three-dimensional network.

Related literature

For general background to tyrosinase, see: Ha et al. (2007 [triangle]); Kubo et al. (2000 [triangle]). For the development of tyrosinase inhibitors, see: Kojima et al. (1995 [triangle]); Cabanes et al. (1994 [triangle]); Casanola-Martin et al. (2006 [triangle]); Son et al. (2000 [triangle]); Iida et al. (1995 [triangle]). For thio­urea derivatives, see: Thanigaimalai et al. (2010 [triangle]); Klabunde et al. (1998 [triangle]); Criton (2006 [triangle]); Daniel (2006 [triangle]); Yi et al. (2009 [triangle]); Liu et al. (2009 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o3303-scheme1.jpg

Experimental

Crystal data

  • C16H18N2O4S
  • M r = 334.38
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o3303-efi1.jpg
  • a = 10.5705 (5) Å
  • b = 12.8195 (7) Å
  • c = 12.4157 (7) Å
  • β = 99.434 (3)°
  • V = 1659.68 (15) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.22 mm−1
  • T = 296 K
  • 0.15 × 0.08 × 0.03 mm

Data collection

  • Bruker SMART CCD area-detector diffractometer
  • 12193 measured reflections
  • 3166 independent reflections
  • 1723 reflections with I > 2σ(I)
  • R int = 0.050

Refinement

  • R[F 2 > 2σ(F 2)] = 0.045
  • wR(F 2) = 0.121
  • S = 0.94
  • 3166 reflections
  • 219 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.50 e Å−3
  • Δρmin = −0.27 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/S160053681004866X/bt5417sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S160053681004866X/bt5417Isup2.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

Melanin production is primary responsible for the skin color, and melanin plays a key role in protecting human skin from the harmful UV-induced skin damages. Tyrosinase is the key enzyme (Ha et al., 2007; Kubo et al., 2000)) that converts tyrosine to melanin and its inhibitors are the target molecules to develop and research anti-pigmentation agents for the application to skin care. Numerous potential tyrosinase inhibitors have been discovered from natural and synthetic sources, such as ascorbic acid (Kojima et al., 1995), kojic acid (Cabanes et al., 1994), arbutin (Casanola-Martin et al., 2006) and tropolone (Son et al., 2000; Iida et al., 1995). Some thiourea derivatives, such as phenylthiourea (Thanigaimalai et al., 2010; Klabunde et al., 1998; Criton, 2006), alkylthiourea (Daniel, 2006), thiosemicarbazone (Yi et al., 2009) and thiosemicarbazide (Liu et al., 2009) have been also reported. During our works on developing potent whitening agents preventing the inadequacies of current whitening agents (poor skin penetration and toxicity) and minimizing the inhibitory effects of melanin creation, we have synthesized the title compound from the reaction of 3,4,5-trimethoxyphenyl isothiocyanate and 4-aminophenol under ambient condition.

The 3,4,5-trimethoxyphenyl moiety is almost planar with r.m.s. deviation of 0.050 Å from the corresponding least-squares plane defined by the ten constituent atoms. The dihedral angle between the phenyl ring and the plane of thiourea moiety is 54.53 (8) °. In the crystal, intermolecular N—H···S, N—H···O, and O—H···S hydrogen bonds link the molecules into a three-dimensional network (Fig. 2, Table 1). The H atoms of the NH groups of thiourea are positioned anti to each other.

Experimental

The 3,4,5-trimethoxyphenyl thiocyanate and 4-aminophenol 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 3,4,5-trimethoxyphenyl isothiocyanate (0.20 g, 0.89 mmol) with 4-aminophenol (0.10 g, 1.10 mmol) in acetonitrile (6 ml). The reaction was completed within 30 min at room temperature. The reaction mixture was filtered rapidly and washed with n-hexane. Removal of the solvent gave a white solid (66% m.p. 499 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 = 0.93–0.96 Å, and with Uiso(H) = 1.2Ueq (C) for aromatic and 1.5Ueq(C) for methyl H atoms.

Figures

Fig. 1.
Molecular structure of (l), showing the atom-numbering scheme and 50% probability ellipsoids.
Fig. 2.
Part of the crystal structure of (I), showing 3-D network of molecules linked by intermolecular N—H···S, N—H···O, and O—H···S hydrogen bonds (dashed lines). ...

Crystal data

C16H18N2O4SF(000) = 704
Mr = 334.38Dx = 1.338 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 2485 reflections
a = 10.5705 (5) Åθ = 2.5–24.0°
b = 12.8195 (7) ŵ = 0.22 mm1
c = 12.4157 (7) ÅT = 296 K
β = 99.434 (3)°Plate, colourless
V = 1659.68 (15) Å30.15 × 0.08 × 0.03 mm
Z = 4

Data collection

Bruker SMART CCD area-detector diffractometerRint = 0.050
[var phi] and ω scansθmax = 26°, θmin = 2.0°
12193 measured reflectionsh = −13→8
3166 independent reflectionsk = −15→8
1723 reflections with I > 2σ(I)l = −12→15

Refinement

Refinement on F20 restraints
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.045w = 1/[σ2(Fo2) + (0.0578P)2] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.121(Δ/σ)max < 0.001
S = 0.94Δρmax = 0.50 e Å3
3166 reflectionsΔρmin = −0.27 e Å3
219 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
C10.2918 (2)0.0884 (2)0.50738 (19)0.0393 (6)
C20.3504 (2)0.1779 (2)0.4769 (2)0.0418 (6)
H20.30750.22140.42290.05*
C30.4737 (2)0.2018 (2)0.5278 (2)0.0433 (7)
C40.5374 (2)0.1378 (2)0.6101 (2)0.0460 (7)
C50.4764 (2)0.04838 (19)0.63858 (19)0.0373 (6)
C60.3541 (2)0.0237 (2)0.5875 (2)0.0397 (6)
H60.314−0.03640.60710.048*
N70.1622 (2)0.06459 (18)0.4621 (2)0.0459 (6)
H70.119 (2)0.045 (2)0.507 (2)0.055 (9)*
C80.1061 (2)0.06515 (19)0.3571 (2)0.0410 (6)
S9−0.05561 (6)0.05352 (6)0.32614 (6)0.0539 (3)
N100.1831 (2)0.0730 (2)0.28268 (18)0.0489 (7)
H100.259 (2)0.0614 (19)0.302 (2)0.051 (8)*
C110.1464 (2)0.0882 (2)0.1678 (2)0.0420 (7)
C120.1835 (2)0.0159 (2)0.0971 (2)0.0486 (7)
H120.2269−0.04410.12410.058*
C130.1559 (2)0.0330 (2)−0.0148 (2)0.0492 (7)
H130.1821−0.015−0.06290.059*
C140.0900 (3)0.1207 (2)−0.0543 (2)0.0505 (7)
C150.0518 (3)0.1923 (2)0.0164 (2)0.0548 (8)
H150.0060.2512−0.01070.066*
C160.0815 (2)0.1766 (2)0.1278 (2)0.0501 (7)
H160.05770.22590.17570.06*
O170.0601 (2)0.14204 (17)−0.16395 (17)0.0751 (7)
H170.067 (3)0.083 (3)−0.211 (3)0.113*
O180.53853 (18)0.28931 (15)0.50440 (16)0.0652 (6)
C190.4781 (3)0.3585 (2)0.4229 (3)0.0756 (10)
H19A0.53480.41550.41510.113*
H19B0.40060.38490.44370.113*
H19C0.4580.3220.35470.113*
O200.6530 (2)0.1626 (2)0.67179 (19)0.0943 (8)
C210.7566 (3)0.1977 (3)0.6305 (4)0.1032 (14)
H21A0.82550.21170.68920.155*
H21B0.73430.26060.58980.155*
H21C0.7830.14570.58320.155*
O220.54582 (15)−0.01140 (14)0.71848 (14)0.0501 (5)
C230.4836 (3)−0.0992 (2)0.7567 (2)0.0669 (9)
H23A0.5424−0.13480.81170.1*
H23B0.456−0.14580.69690.1*
H23C0.4106−0.07610.78710.1*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0324 (13)0.0531 (16)0.0315 (16)−0.0018 (13)0.0026 (12)−0.0023 (13)
C20.0410 (15)0.0485 (16)0.0356 (16)0.0011 (14)0.0058 (13)0.0035 (12)
C30.0436 (15)0.0451 (16)0.0428 (17)−0.0060 (14)0.0114 (14)−0.0013 (14)
C40.0330 (14)0.0615 (18)0.0408 (17)−0.0099 (14)−0.0024 (13)−0.0017 (14)
C50.0342 (13)0.0489 (16)0.0289 (15)0.0021 (13)0.0054 (12)0.0002 (12)
C60.0350 (14)0.0475 (15)0.0368 (16)−0.0040 (13)0.0061 (12)0.0015 (12)
N70.0326 (12)0.0695 (17)0.0347 (15)−0.0071 (12)0.0027 (12)0.0069 (12)
C80.0348 (13)0.0508 (16)0.0358 (17)−0.0001 (13)0.0008 (13)0.0021 (13)
S90.0326 (4)0.0859 (6)0.0421 (5)−0.0061 (4)0.0031 (3)0.0022 (4)
N100.0282 (12)0.0802 (18)0.0378 (16)0.0027 (13)0.0036 (11)0.0030 (12)
C110.0302 (13)0.0629 (18)0.0328 (17)−0.0070 (13)0.0050 (12)0.0018 (14)
C120.0377 (15)0.0613 (18)0.0468 (19)0.0016 (14)0.0074 (14)0.0023 (15)
C130.0494 (16)0.0583 (18)0.0414 (19)−0.0069 (15)0.0120 (14)−0.0037 (14)
C140.0537 (17)0.0601 (19)0.0368 (18)−0.0173 (16)0.0043 (15)0.0055 (15)
C150.0609 (18)0.0531 (18)0.050 (2)−0.0024 (15)0.0070 (16)0.0067 (15)
C160.0483 (16)0.0567 (18)0.045 (2)−0.0036 (15)0.0070 (14)−0.0031 (14)
O170.1081 (19)0.0753 (15)0.0396 (14)−0.0098 (14)0.0056 (13)0.0103 (11)
O180.0618 (13)0.0624 (13)0.0684 (14)−0.0216 (11)0.0022 (11)0.0138 (11)
C190.087 (2)0.0554 (19)0.086 (3)−0.0068 (18)0.020 (2)0.0201 (19)
O200.0543 (14)0.133 (2)0.0873 (18)−0.0382 (14)−0.0146 (13)0.0378 (15)
C210.049 (2)0.092 (3)0.163 (4)−0.006 (2)0.001 (2)0.020 (3)
O220.0386 (10)0.0654 (12)0.0443 (12)0.0019 (9)0.0011 (9)0.0128 (10)
C230.0617 (19)0.078 (2)0.060 (2)0.0053 (18)0.0080 (17)0.0287 (17)

Geometric parameters (Å, °)

C1—C61.377 (3)C12—H120.93
C1—C21.386 (3)C13—C141.371 (4)
C1—N71.426 (3)C13—H130.93
C2—C31.387 (3)C14—O171.374 (3)
C2—H20.93C14—C151.376 (4)
C3—O181.371 (3)C15—C161.381 (4)
C3—C41.394 (3)C15—H150.93
C4—O201.370 (3)C16—H160.93
C4—C51.389 (3)O17—H170.97 (3)
C5—O221.368 (3)O18—C191.416 (3)
C5—C61.380 (3)C19—H19A0.96
C6—H60.93C19—H19B0.96
N7—C81.341 (3)C19—H19C0.96
N7—H70.81 (3)O20—C211.360 (4)
C8—N101.331 (3)C21—H21A0.96
C8—S91.696 (2)C21—H21B0.96
N10—C111.429 (3)C21—H21C0.96
N10—H100.81 (2)O22—C231.423 (3)
C11—C161.375 (3)C23—H23A0.96
C11—C121.377 (3)C23—H23B0.96
C12—C131.389 (3)C23—H23C0.96
C6—C1—C2120.9 (2)C14—C13—H13120.1
C6—C1—N7118.1 (2)C12—C13—H13120.1
C2—C1—N7120.9 (2)C13—C14—O17122.6 (3)
C1—C2—C3119.1 (2)C13—C14—C15120.3 (3)
C1—C2—H2120.4O17—C14—C15117.1 (3)
C3—C2—H2120.4C14—C15—C16120.0 (3)
O18—C3—C2123.3 (2)C14—C15—H15120
O18—C3—C4116.0 (2)C16—C15—H15120
C2—C3—C4120.6 (2)C11—C16—C15120.0 (3)
O20—C4—C5117.2 (2)C11—C16—H16120
O20—C4—C3123.5 (2)C15—C16—H16120
C5—C4—C3118.9 (2)C14—O17—H17115 (2)
O22—C5—C6123.7 (2)C3—O18—C19118.8 (2)
O22—C5—C4115.5 (2)O18—C19—H19A109.5
C6—C5—C4120.7 (2)O18—C19—H19B109.5
C1—C6—C5119.7 (2)H19A—C19—H19B109.5
C1—C6—H6120.2O18—C19—H19C109.5
C5—C6—H6120.2H19A—C19—H19C109.5
C8—N7—C1128.7 (2)H19B—C19—H19C109.5
C8—N7—H7117.2 (19)C21—O20—C4124.5 (3)
C1—N7—H7113.9 (18)O20—C21—H21A109.5
N10—C8—N7116.9 (2)O20—C21—H21B109.5
N10—C8—S9123.9 (2)H21A—C21—H21B109.5
N7—C8—S9119.23 (19)O20—C21—H21C109.5
C8—N10—C11127.3 (2)H21A—C21—H21C109.5
C8—N10—H10117.7 (18)H21B—C21—H21C109.5
C11—N10—H10114.6 (18)C5—O22—C23117.54 (19)
C16—C11—C12120.1 (2)O22—C23—H23A109.5
C16—C11—N10120.7 (2)O22—C23—H23B109.5
C12—C11—N10119.1 (2)H23A—C23—H23B109.5
C11—C12—C13119.8 (3)O22—C23—H23C109.5
C11—C12—H12120.1H23A—C23—H23C109.5
C13—C12—H12120.1H23B—C23—H23C109.5
C14—C13—C12119.8 (3)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N7—H7···S9i0.81 (3)2.61 (3)3.383 (3)160 (2)
N10—H10···O22ii0.81 (2)2.22 (3)2.975 (3)156 (2)
O17—H17···S9iii0.97 (3)2.25 (4)3.211 (2)173 (3)

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BT5417).

References

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