1-(2-Hy­droxy­eth­yl)-3-(3-meth­oxy­phen­yl)thio­urea

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

doi:10.1107/S1600536810034665

. 2010 Sep 4;66(Pt 10):o2487–o2488. doi: 10.1107/S1600536810034665

1-(2-Hydroxyethyl)-3-(3-methoxyphenyl)thiourea

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

PMCID: PMC2983277 PMID: 21587487

Abstract

In the title compound, C₁₀H₁₄N₂O₃S, the 3-methoxyphenyl unit is almost planar, with an r.m.s. deviation of 0.013 Å. The dihedral angle between the benzene ring and the plane of the thiourea unit is 62.57 (4)°. In the crystal, N—H⋯O and O—H⋯S hydrogen bonds link the molecules into a three-dimensional network.

Related literature

For general background to melanin, see: Ha et al. (2007 ▶). For the development of potent inhibitory agents of tyrosinase, 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

C₁₀H₁₄N₂O₂S
M _r = 226.29
Monoclinic,
a = 10.9894 (3) Å
b = 8.0759 (2) Å
c = 12.8067 (4) Å
β = 102.920 (1)°
V = 1107.81 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.27 mm⁻¹
T = 296 K
0.37 × 0.21 × 0.2 mm

Data collection

Bruker SMART CCD area-detector diffractometer
8965 measured reflections
2478 independent reflections
2013 reflections with I > 2σ(I)
R _int = 0.059

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.107
S = 1.08
2478 reflections
148 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.36 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/S1600536810034665/tk2706sup1.cif

e-66-o2487-sup1.cif^{(13.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810034665/tk2706Isup2.hkl

e-66-o2487-Isup2.hkl^{(119.3KB, 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⋯O13ⁱ	0.824 (19)	2.059 (19)	2.8619 (16)	164.6 (17)
N10—H10⋯O14ⁱⁱ	0.817 (19)	2.316 (19)	3.0877 (17)	157.8 (15)
O13—H13⋯S9ⁱⁱⁱ	0.81 (2)	2.47 (2)	3.2532 (14)	163 (2)

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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 is the pigment responsible for the color of human skin and it is formed through a series of oxidative reactions in the presence of key enzyme tyrosinase (Ha et al., 2007) that converts tyrosine into melanin. It is secreted by melanocyte cells distributed in the basal layer of the dermis. Its role is to protect the skin from ultraviolet (UV) damage by absorbing the UV sunlight and removing reactive oxygen species. Therefore, its inhibitors are target molecules for developing anti-pigmentation agents. 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 described. However, only few of the reported compounds are used in medicinal and cosmetic products because of their lower activities, poor skin penetration, or serious side effects. Consequently, there is still a need to search and develop novel tyrosinase inhibitors with better activities together with lower side effects. To complement the inadequacy of current whitening agents and maximize the effect of inhibition of melanin creation, we have synthesized the title compound, (I), from the reaction of 3-methoxyphenyl isothiocyanate and ethanolamine under ambient condition. Here, the crystal structure of (I) is described (Fig. 1).

The 3-methoxyphenyl unit is essentially planar, with a r.m.s. deviation of 0.013 Å from the corresponding least-squares plane defined by the eight constituent atoms. The dihedral angle between the benzene ring and the plane of the thiourea moiety is 62.57 (4) °. In the crystal, N—H···O and O—H···S hydrogen bonds link the molecules into a 3-D network (Fig. 2, Table 1). The H atoms of the NH groups of thiourea are positioned anti to each other.

Experimental

Ethanolamine and 3-methoxyphenyl isothiocyanate were purchased from Sigma Chemical Co. Solvents used for organic synthesis were distilled 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-methoxyphenyl isothiocyanate (0.4 ml, 1 mmol) with ethanolamine (0.2 ml, 1.2 mmol) in acetonitrile (6 ml). The reaction was completed within 30 min at room temperature. The reaction mixture was filtered and washed with dry n-hexane. Removal of the solvent under vacuum gave a white solid (80%, m.p. 398 K). Single crystals were obtained by slow evaporation of the ethanol solution held at room temperature.