2-(2,5-Dimeth­oxy­phen­yl)-N-[2-(4-hy­droxy­phen­yl)eth­yl]acetamide

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

doi:10.1107/S1600536812008975

. 2012 Mar 7;68(Pt 4):o966. doi: 10.1107/S1600536812008975

2-(2,5-Dimethoxyphenyl)-N-[2-(4-hydroxyphenyl)ethyl]acetamide

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

PMCID: PMC3343941 PMID: 22590022

Abstract

In the title compound, C₁₈H₂₁NO₄, the dihedral angles between the acetamide group and the methoxy- and hydroxy-substitured benzene rings are 80.81 (5) and 8.19 (12)°, respectively. The benzene rings are twisted with respect to each other, making a dihedral angle of 72.89 (5)°. In the crystal, 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 ▶). For the development of tyrosinase inhibitors, see: Lemic-Stojcevic et al. (1995 ▶); Battaini et al. (2000 ▶); Cabanes et al. (1994 ▶); Thanigaimalai et al. (2010 ▶).

Experimental

Crystal data

C₁₈H₂₁NO₄
M _r = 315.36
Orthorhombic,
a = 8.1628 (8) Å
b = 12.0701 (11) Å
c = 17.0176 (16) Å
V = 1676.7 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 296 K
0.3 × 0.23 × 0.1 mm

Data collection

Bruker SMART CCD area-detector diffractometer
8417 measured reflections
3638 independent reflections
2352 reflections with I > 2σ(I)
R _int = 0.063

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.088
S = 0.87
3638 reflections
216 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.11 e Å⁻³
Δρ_min = −0.12 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: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812008975/tk5063sup1.cif

e-68-0o966-sup1.cif^{(22.7KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812008975/tk5063Isup2.hkl

e-68-0o966-Isup2.hkl^{(174.8KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812008975/tk5063Isup3.cml

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
N10—H10⋯O19ⁱ	0.88 (2)	2.16 (2)	3.023 (2)	165.4 (19)
O19—H19⋯O9ⁱⁱ	0.87 (3)	1.76 (3)	2.6289 (19)	174 (3)

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

Acknowledgments

We wish to thank the DBIO company for partial support of this work.

supplementary crystallographic information

Comment

Tyrosinase is a copper containing enzyme which acts as a catalyst in two different reactions involving the hydroxylation of monophenols to o-diphenols and the oxidation of the o-diphenols to o-quinones. This class of enzyme is widely distributed in the plant, animal and microorganism kingdoms (Kubo et al., 2000), and its inhibition is one of the major strategies in developing new whitening agents. Over the last few decades, various tyrosinase inhibitors, including azelaic acid (Lemic-Stojcevic et al., 1995), kojic acid (Battaini et al., 2000), arbutin (Cabanes et al., 1994), and N-phenylthiourea (PTU) (Thanigaimalai et al., 2010) have been studied. But some of their individual activities are either not potent enough to be considered of practical use or not compatible with safety regulations for food and cosmetic additives. In our continuing search for tyrosinase inhibitors, we have synthesized the title compound, (I), from the reaction of 2,5-dimethoxyphenyl acetyl chloride and tyramine under ambient conditions. Herein, the crystal structure of (I) is described (Fig. 1).

The 2,4-dimethoxyphenyl and 3-hydroxyphenyl moieties are almost planar with r.m.s. deviations of 0.008 and 0.009 Å, respectively, from their corresponding least-squares planes. The dihedral angles between the acetamide group (C7–N10) and the benzene rings (C1–C6 + O20 and O22; and C12–O19) are 80.81 (5) and 8.19 (12)°, respectively. The benzene groups are twisted with respect to each other making a dihedral angle of 72.89 (5)°. The presence of intermolecular N10—H10···O19ⁱ and O19—H19···O9ⁱⁱ [symmetry codes: (i) x - 1/2, -y + 3/2, -z + 1, (ii) -x + 3/2, -y + 1, z + 1/2] hydrogen bonds link the molecules into a three-dimensional network (Fig. 2 and Table 1).

Experimental

The starting materials, 2,5-dimethoxyphenyl acetyl chloride and tyramine, were purchased from Sigma Chemical Co. Solvents 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 was prepared from the reaction of 2,5-dimethoxyphenyl acetyl chloride (0.21 g, 1.0 mmol) and tyramine (0.14 g, 1.0 mmol) by simple substitution in THF (6 ml) triethylamine (0.12 g, 1.2 mmol). The solvent was removed under reduced pressure. The mixture was purified by column chromatography on silica gel (2:1 dichloromethane/ethylacetate) to give the title compound. Colourless crystals were obtained by slow evaporation of its ethanol solution at room temperature.