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

Hyeong Choi; Byung Hee Han; Yong Suk Shim; Sung Kwon Kang; Chang Keun Sung

doi:10.1107/S160053681004866X

. 2010 Nov 27;66(Pt 12):o3303–o3304. doi: 10.1107/S160053681004866X

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

Hyeong Choi ^a, Byung Hee Han ^a, Yong Suk Shim ^a, Sung Kwon Kang ^a,^*, Chang Keun Sung ^b

PMCID: PMC3011736 PMID: 21589582

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

Experimental

Crystal data

C₁₆H₁₈N₂O₄S
M _r = 334.38
Monoclinic,
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
Δρ_max = 0.50 e Å⁻³
Δρ_min = −0.27 e Å⁻³

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

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053681004866X/bt5417sup1.cif

e-66-o3303-sup1.cif^{(16KB, cif)}

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

e-66-o3303-Isup2.hkl^{(152.2KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N7—H7⋯S9ⁱ	0.81 (3)	2.61 (3)	3.383 (3)	160 (2)
N10—H10⋯O22ⁱⁱ	0.81 (2)	2.22 (3)	2.975 (3)	156 (2)
O17—H17⋯S9ⁱⁱⁱ	0.97 (3)	2.25 (4)	3.211 (2)	173 (3)

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

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.