1-(4-Hy-droxy-phen-yl)-3-(3,4,5-tri-methoxy-phen-yl)thio-urea.

In the title compound, C(16)H(18)N(2)O(4)S, the dihedral angle between the hy-droxy-phenyl ring and the plane of the thio-urea moiety is 54.53 (8)°. The H atoms of the NH groups of thio-urea are positioned anti to each other. In the crystal, inter-molecular N-H⋯S, N-H⋯O, and O-H⋯S hydrogen bonds link the mol-ecules 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 = 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

Δρmax = 0.50 e Å−3

Δρmin = −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 ▶).

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

C16H18N2O4S	F(000) = 704
Mr = 334.38	Dx = 1.338 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 2485 reflections
a = 10.5705 (5) Å	θ = 2.5–24.0°
b = 12.8195 (7) Å	µ = 0.22 mm−1
c = 12.4157 (7) Å	T = 296 K
β = 99.434 (3)°	Plate, colourless
V = 1659.68 (15) Å3	0.15 × 0.08 × 0.03 mm
Z = 4

Bruker SMART CCD area-detector diffractometer	Rint = 0.050
φ and ω scans	θmax = 26°, θmin = 2.0°
12193 measured reflections	h = −13→8
3166 independent reflections	k = −15→8
1723 reflections with I > 2σ(I)	l = −12→15

Refinement on F2	0 restraints
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.045	w = 1/[σ2(Fo2) + (0.0578P)2] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.121	(Δ/σ)max < 0.001
S = 0.94	Δρmax = 0.50 e Å−3
3166 reflections	Δρmin = −0.27 e Å−3
219 parameters

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.

	x	y	z	Uiso*/Ueq
C1	0.2918 (2)	0.0884 (2)	0.50738 (19)	0.0393 (6)
C2	0.3504 (2)	0.1779 (2)	0.4769 (2)	0.0418 (6)
H2	0.3075	0.2214	0.4229	0.05*
C3	0.4737 (2)	0.2018 (2)	0.5278 (2)	0.0433 (7)
C4	0.5374 (2)	0.1378 (2)	0.6101 (2)	0.0460 (7)
C5	0.4764 (2)	0.04838 (19)	0.63858 (19)	0.0373 (6)
C6	0.3541 (2)	0.0237 (2)	0.5875 (2)	0.0397 (6)
H6	0.314	−0.0364	0.6071	0.048*
N7	0.1622 (2)	0.06459 (18)	0.4621 (2)	0.0459 (6)
H7	0.119 (2)	0.045 (2)	0.507 (2)	0.055 (9)*
C8	0.1061 (2)	0.06515 (19)	0.3571 (2)	0.0410 (6)
S9	−0.05561 (6)	0.05352 (6)	0.32614 (6)	0.0539 (3)
N10	0.1831 (2)	0.0730 (2)	0.28268 (18)	0.0489 (7)
H10	0.259 (2)	0.0614 (19)	0.302 (2)	0.051 (8)*
C11	0.1464 (2)	0.0882 (2)	0.1678 (2)	0.0420 (7)
C12	0.1835 (2)	0.0159 (2)	0.0971 (2)	0.0486 (7)
H12	0.2269	−0.0441	0.1241	0.058*
C13	0.1559 (2)	0.0330 (2)	−0.0148 (2)	0.0492 (7)
H13	0.1821	−0.015	−0.0629	0.059*
C14	0.0900 (3)	0.1207 (2)	−0.0543 (2)	0.0505 (7)
C15	0.0518 (3)	0.1923 (2)	0.0164 (2)	0.0548 (8)
H15	0.006	0.2512	−0.0107	0.066*
C16	0.0815 (2)	0.1766 (2)	0.1278 (2)	0.0501 (7)
H16	0.0577	0.2259	0.1757	0.06*
O17	0.0601 (2)	0.14204 (17)	−0.16395 (17)	0.0751 (7)
H17	0.067 (3)	0.083 (3)	−0.211 (3)	0.113*
O18	0.53853 (18)	0.28931 (15)	0.50440 (16)	0.0652 (6)
C19	0.4781 (3)	0.3585 (2)	0.4229 (3)	0.0756 (10)
H19A	0.5348	0.4155	0.4151	0.113*
H19B	0.4006	0.3849	0.4437	0.113*
H19C	0.458	0.322	0.3547	0.113*
O20	0.6530 (2)	0.1626 (2)	0.67179 (19)	0.0943 (8)
C21	0.7566 (3)	0.1977 (3)	0.6305 (4)	0.1032 (14)
H21A	0.8255	0.2117	0.6892	0.155*
H21B	0.7343	0.2606	0.5898	0.155*
H21C	0.783	0.1457	0.5832	0.155*
O22	0.54582 (15)	−0.01140 (14)	0.71848 (14)	0.0501 (5)
C23	0.4836 (3)	−0.0992 (2)	0.7567 (2)	0.0669 (9)
H23A	0.5424	−0.1348	0.8117	0.1*
H23B	0.456	−0.1458	0.6969	0.1*
H23C	0.4106	−0.0761	0.7871	0.1*

	U11	U22	U33	U12	U13	U23
C1	0.0324 (13)	0.0531 (16)	0.0315 (16)	−0.0018 (13)	0.0026 (12)	−0.0023 (13)
C2	0.0410 (15)	0.0485 (16)	0.0356 (16)	0.0011 (14)	0.0058 (13)	0.0035 (12)
C3	0.0436 (15)	0.0451 (16)	0.0428 (17)	−0.0060 (14)	0.0114 (14)	−0.0013 (14)
C4	0.0330 (14)	0.0615 (18)	0.0408 (17)	−0.0099 (14)	−0.0024 (13)	−0.0017 (14)
C5	0.0342 (13)	0.0489 (16)	0.0289 (15)	0.0021 (13)	0.0054 (12)	0.0002 (12)
C6	0.0350 (14)	0.0475 (15)	0.0368 (16)	−0.0040 (13)	0.0061 (12)	0.0015 (12)
N7	0.0326 (12)	0.0695 (17)	0.0347 (15)	−0.0071 (12)	0.0027 (12)	0.0069 (12)
C8	0.0348 (13)	0.0508 (16)	0.0358 (17)	−0.0001 (13)	0.0008 (13)	0.0021 (13)
S9	0.0326 (4)	0.0859 (6)	0.0421 (5)	−0.0061 (4)	0.0031 (3)	0.0022 (4)
N10	0.0282 (12)	0.0802 (18)	0.0378 (16)	0.0027 (13)	0.0036 (11)	0.0030 (12)
C11	0.0302 (13)	0.0629 (18)	0.0328 (17)	−0.0070 (13)	0.0050 (12)	0.0018 (14)
C12	0.0377 (15)	0.0613 (18)	0.0468 (19)	0.0016 (14)	0.0074 (14)	0.0023 (15)
C13	0.0494 (16)	0.0583 (18)	0.0414 (19)	−0.0069 (15)	0.0120 (14)	−0.0037 (14)
C14	0.0537 (17)	0.0601 (19)	0.0368 (18)	−0.0173 (16)	0.0043 (15)	0.0055 (15)
C15	0.0609 (18)	0.0531 (18)	0.050 (2)	−0.0024 (15)	0.0070 (16)	0.0067 (15)
C16	0.0483 (16)	0.0567 (18)	0.045 (2)	−0.0036 (15)	0.0070 (14)	−0.0031 (14)
O17	0.1081 (19)	0.0753 (15)	0.0396 (14)	−0.0098 (14)	0.0056 (13)	0.0103 (11)
O18	0.0618 (13)	0.0624 (13)	0.0684 (14)	−0.0216 (11)	0.0022 (11)	0.0138 (11)
C19	0.087 (2)	0.0554 (19)	0.086 (3)	−0.0068 (18)	0.020 (2)	0.0201 (19)
O20	0.0543 (14)	0.133 (2)	0.0873 (18)	−0.0382 (14)	−0.0146 (13)	0.0378 (15)
C21	0.049 (2)	0.092 (3)	0.163 (4)	−0.006 (2)	0.001 (2)	0.020 (3)
O22	0.0386 (10)	0.0654 (12)	0.0443 (12)	0.0019 (9)	0.0011 (9)	0.0128 (10)
C23	0.0617 (19)	0.078 (2)	0.060 (2)	0.0053 (18)	0.0080 (17)	0.0287 (17)

C1—C6	1.377 (3)	C12—H12	0.93
C1—C2	1.386 (3)	C13—C14	1.371 (4)
C1—N7	1.426 (3)	C13—H13	0.93
C2—C3	1.387 (3)	C14—O17	1.374 (3)
C2—H2	0.93	C14—C15	1.376 (4)
C3—O18	1.371 (3)	C15—C16	1.381 (4)
C3—C4	1.394 (3)	C15—H15	0.93
C4—O20	1.370 (3)	C16—H16	0.93
C4—C5	1.389 (3)	O17—H17	0.97 (3)
C5—O22	1.368 (3)	O18—C19	1.416 (3)
C5—C6	1.380 (3)	C19—H19A	0.96
C6—H6	0.93	C19—H19B	0.96
N7—C8	1.341 (3)	C19—H19C	0.96
N7—H7	0.81 (3)	O20—C21	1.360 (4)
C8—N10	1.331 (3)	C21—H21A	0.96
C8—S9	1.696 (2)	C21—H21B	0.96
N10—C11	1.429 (3)	C21—H21C	0.96
N10—H10	0.81 (2)	O22—C23	1.423 (3)
C11—C16	1.375 (3)	C23—H23A	0.96
C11—C12	1.377 (3)	C23—H23B	0.96
C12—C13	1.389 (3)	C23—H23C	0.96
C6—C1—C2	120.9 (2)	C14—C13—H13	120.1
C6—C1—N7	118.1 (2)	C12—C13—H13	120.1
C2—C1—N7	120.9 (2)	C13—C14—O17	122.6 (3)
C1—C2—C3	119.1 (2)	C13—C14—C15	120.3 (3)
C1—C2—H2	120.4	O17—C14—C15	117.1 (3)
C3—C2—H2	120.4	C14—C15—C16	120.0 (3)
O18—C3—C2	123.3 (2)	C14—C15—H15	120
O18—C3—C4	116.0 (2)	C16—C15—H15	120
C2—C3—C4	120.6 (2)	C11—C16—C15	120.0 (3)
O20—C4—C5	117.2 (2)	C11—C16—H16	120
O20—C4—C3	123.5 (2)	C15—C16—H16	120
C5—C4—C3	118.9 (2)	C14—O17—H17	115 (2)
O22—C5—C6	123.7 (2)	C3—O18—C19	118.8 (2)
O22—C5—C4	115.5 (2)	O18—C19—H19A	109.5
C6—C5—C4	120.7 (2)	O18—C19—H19B	109.5
C1—C6—C5	119.7 (2)	H19A—C19—H19B	109.5
C1—C6—H6	120.2	O18—C19—H19C	109.5
C5—C6—H6	120.2	H19A—C19—H19C	109.5
C8—N7—C1	128.7 (2)	H19B—C19—H19C	109.5
C8—N7—H7	117.2 (19)	C21—O20—C4	124.5 (3)
C1—N7—H7	113.9 (18)	O20—C21—H21A	109.5
N10—C8—N7	116.9 (2)	O20—C21—H21B	109.5
N10—C8—S9	123.9 (2)	H21A—C21—H21B	109.5
N7—C8—S9	119.23 (19)	O20—C21—H21C	109.5
C8—N10—C11	127.3 (2)	H21A—C21—H21C	109.5
C8—N10—H10	117.7 (18)	H21B—C21—H21C	109.5
C11—N10—H10	114.6 (18)	C5—O22—C23	117.54 (19)
C16—C11—C12	120.1 (2)	O22—C23—H23A	109.5
C16—C11—N10	120.7 (2)	O22—C23—H23B	109.5
C12—C11—N10	119.1 (2)	H23A—C23—H23B	109.5
C11—C12—C13	119.8 (3)	O22—C23—H23C	109.5
C11—C12—H12	120.1	H23A—C23—H23C	109.5
C13—C12—H12	120.1	H23B—C23—H23C	109.5
C14—C13—C12	119.8 (3)

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)

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)

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