organic compounds
1-[3-(Hydroxymethyl)phenyl]-3-phenylurea
aDepartment of Chemistry, Chungnam National University, Daejeon 305-764, Republic of Korea, and bDepartment of Food Science and Technology, Chungnam National University, Daejeon 305-764, Republic of Korea
*Correspondence e-mail: skkang@cnu.ac.kr
In the title compound, C14H14N2O2, the dihedral angle between the benzene rings is 23.6 (1)°. The H atoms of the urea NH groups are positioned syn to each other. In the crystal, intermolecular N—H⋯O and O—H⋯O hydrogen bonds link the molecules into a three-dimensional network.
Related literature
For general background to melanin, see: Kubo et al. (2000); Claus & Decker (2006). For the development of tyrosinase inhibitors, see: Khan et al. (2006); Kojima et al. (1995); Cabanes et al. (1994); Casañola-Martin et al. (2006); Son et al. (2000); Hong et al. (2008); Lee et al. (2007); Yi et al. (2010); Choi et al. (2010).
Experimental
Crystal data
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Data collection
|
Refinement
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Data collection: SMART (Bruker, 2002); cell 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).
Supporting information
10.1107/S1600536811028315/im2305sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536811028315/im2305Isup2.hkl
Supporting information file. DOI: 10.1107/S1600536811028315/im2305Isup3.cml
3-Aminobenzyl alcohol and phenyl isocyanate 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 used without further purification. The title compound was prepared from the reaction of 3-aminobenzyl alcohol (0.2 g, 1.0 mmol) with phenyl isocyanate (0.23 g, 1.2 mmol) in acetonitrile (6 ml) with stirring. The reaction was completed within 30 min at room temperature under 1 atm of N2 gas. The solvents were removed under reduced pressure. The solids collected and washed with dichloromethane. Removal of the solvent gave a white solid (73%, m.p. 446 K). Single crystals were obtained from an ethanolic solution by slow evaporation of the solvent at room temperature.
H atoms of NH and OH groups were located in a difference Fourier map and refined freely. Rremaining H atoms were positioned geometrically and refined using a riding model with C—H = 0.93–0.97 Å, and with Uiso(H) = 1.2Ueq (C) for aromatic and methylene H atoms.
Data collection: SMART (Bruker, 2002); cell
SAINT (Bruker, 2002); data reduction: SAINT (Bruker, 2002); 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).C14H14N2O2 | F(000) = 512 |
Mr = 242.27 | Dx = 1.334 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ybc | Cell parameters from 2624 reflections |
a = 14.6207 (8) Å | θ = 3.2–28.0° |
b = 7.0692 (4) Å | µ = 0.09 mm−1 |
c = 12.4019 (5) Å | T = 296 K |
β = 109.818 (3)° | Plate, colourless |
V = 1205.90 (11) Å3 | 0.22 × 0.21 × 0.05 mm |
Z = 4 |
Bruker SMART CCD area-detector diffractometer | Rint = 0.052 |
ϕ and ω scans | θmax = 27.5°, θmin = 3.0° |
9960 measured reflections | h = −15→18 |
2694 independent reflections | k = −9→6 |
1664 reflections with I > 2σ(I) | l = −16→9 |
Refinement on F2 | 0 restraints |
Least-squares matrix: full | H atoms treated by a mixture of independent and constrained refinement |
R[F2 > 2σ(F2)] = 0.041 | w = 1/[σ2(Fo2) + (0.0584P)2] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.111 | (Δ/σ)max < 0.001 |
S = 0.93 | Δρmax = 0.14 e Å−3 |
2694 reflections | Δρmin = −0.21 e Å−3 |
175 parameters |
C14H14N2O2 | V = 1205.90 (11) Å3 |
Mr = 242.27 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 14.6207 (8) Å | µ = 0.09 mm−1 |
b = 7.0692 (4) Å | T = 296 K |
c = 12.4019 (5) Å | 0.22 × 0.21 × 0.05 mm |
β = 109.818 (3)° |
Bruker SMART CCD area-detector diffractometer | 1664 reflections with I > 2σ(I) |
9960 measured reflections | Rint = 0.052 |
2694 independent reflections |
R[F2 > 2σ(F2)] = 0.041 | 0 restraints |
wR(F2) = 0.111 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.93 | Δρmax = 0.14 e Å−3 |
2694 reflections | Δρmin = −0.21 e Å−3 |
175 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 | 0.13667 (11) | 0.36148 (19) | 0.11590 (11) | 0.0385 (3) | |
C2 | 0.07277 (11) | 0.2820 (2) | 0.01677 (13) | 0.0471 (4) | |
H2 | 0.0933 | 0.2595 | −0.0453 | 0.057* | |
C3 | −0.02094 (12) | 0.2359 (2) | 0.00922 (14) | 0.0546 (4) | |
H3 | −0.0632 | 0.1839 | −0.0581 | 0.066* | |
C4 | −0.05198 (12) | 0.2664 (2) | 0.10023 (15) | 0.0581 (5) | |
H4 | −0.1149 | 0.2343 | 0.0955 | 0.07* | |
C5 | 0.01144 (13) | 0.3456 (3) | 0.19916 (15) | 0.0619 (5) | |
H5 | −0.0093 | 0.3672 | 0.2611 | 0.074* | |
C6 | 0.10517 (12) | 0.3932 (2) | 0.20757 (12) | 0.0524 (4) | |
H6 | 0.147 | 0.4464 | 0.2748 | 0.063* | |
N7 | 0.22912 (9) | 0.41144 (18) | 0.11382 (11) | 0.0442 (3) | |
H7 | 0.2359 (11) | 0.410 (2) | 0.0471 (14) | 0.049 (4)* | |
C8 | 0.31390 (11) | 0.42001 (18) | 0.20514 (11) | 0.0381 (3) | |
O9 | 0.31723 (8) | 0.41011 (14) | 0.30535 (8) | 0.0495 (3) | |
N10 | 0.39322 (9) | 0.44032 (17) | 0.17245 (10) | 0.0436 (3) | |
H10 | 0.3815 (11) | 0.444 (2) | 0.0964 (15) | 0.057 (5)* | |
C11 | 0.49231 (11) | 0.43970 (18) | 0.24098 (11) | 0.0369 (3) | |
C12 | 0.52658 (11) | 0.44241 (19) | 0.35949 (12) | 0.0454 (4) | |
H12 | 0.4834 | 0.4428 | 0.3999 | 0.055* | |
C13 | 0.62598 (12) | 0.4446 (2) | 0.41732 (13) | 0.0516 (4) | |
H13 | 0.6491 | 0.4462 | 0.497 | 0.062* | |
C14 | 0.69114 (12) | 0.4444 (2) | 0.35936 (13) | 0.0481 (4) | |
H14 | 0.7576 | 0.4466 | 0.3997 | 0.058* | |
C15 | 0.65760 (11) | 0.44079 (19) | 0.24059 (12) | 0.0426 (4) | |
C16 | 0.55875 (11) | 0.43755 (19) | 0.18285 (12) | 0.0423 (4) | |
H16 | 0.5359 | 0.4338 | 0.1032 | 0.051* | |
C17 | 0.72705 (12) | 0.4432 (2) | 0.17456 (14) | 0.0554 (4) | |
H17A | 0.7921 | 0.4684 | 0.2272 | 0.066* | |
H17B | 0.7276 | 0.319 | 0.1415 | 0.066* | |
O18 | 0.70325 (8) | 0.58030 (19) | 0.08550 (9) | 0.0559 (3) | |
H18 | 0.6949 (15) | 0.685 (3) | 0.1155 (18) | 0.094 (8)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0402 (9) | 0.0407 (8) | 0.0384 (7) | 0.0035 (6) | 0.0184 (6) | 0.0040 (6) |
C2 | 0.0471 (10) | 0.0508 (9) | 0.0476 (8) | 0.0011 (7) | 0.0216 (7) | −0.0047 (7) |
C3 | 0.0484 (11) | 0.0514 (10) | 0.0634 (10) | −0.0044 (8) | 0.0181 (8) | −0.0058 (8) |
C4 | 0.0434 (11) | 0.0665 (11) | 0.0697 (11) | 0.0000 (8) | 0.0260 (9) | 0.0141 (9) |
C5 | 0.0524 (12) | 0.0909 (13) | 0.0525 (10) | 0.0108 (10) | 0.0309 (9) | 0.0147 (9) |
C6 | 0.0459 (11) | 0.0747 (11) | 0.0400 (8) | 0.0060 (8) | 0.0190 (7) | 0.0029 (8) |
N7 | 0.0395 (8) | 0.0641 (9) | 0.0327 (6) | −0.0023 (6) | 0.0169 (6) | 0.0007 (6) |
C8 | 0.0433 (9) | 0.0383 (8) | 0.0361 (7) | −0.0014 (6) | 0.0176 (6) | −0.0006 (6) |
O9 | 0.0509 (7) | 0.0673 (7) | 0.0339 (5) | −0.0055 (5) | 0.0193 (5) | −0.0011 (5) |
N10 | 0.0411 (8) | 0.0609 (8) | 0.0315 (6) | −0.0035 (6) | 0.0159 (5) | 0.0003 (6) |
C11 | 0.0389 (9) | 0.0362 (8) | 0.0353 (7) | −0.0021 (6) | 0.0121 (6) | −0.0006 (6) |
C12 | 0.0494 (11) | 0.0538 (9) | 0.0361 (7) | −0.0015 (7) | 0.0185 (7) | −0.0032 (7) |
C13 | 0.0521 (11) | 0.0638 (11) | 0.0354 (7) | 0.0000 (8) | 0.0103 (7) | −0.0011 (7) |
C14 | 0.0424 (10) | 0.0532 (10) | 0.0452 (8) | 0.0018 (7) | 0.0103 (7) | −0.0009 (7) |
C15 | 0.0436 (10) | 0.0410 (8) | 0.0455 (8) | 0.0011 (7) | 0.0181 (7) | −0.0005 (6) |
C16 | 0.0421 (10) | 0.0507 (9) | 0.0354 (7) | −0.0029 (7) | 0.0148 (6) | −0.0011 (6) |
C17 | 0.0457 (11) | 0.0697 (11) | 0.0539 (9) | 0.0013 (8) | 0.0210 (8) | −0.0028 (8) |
O18 | 0.0630 (8) | 0.0707 (9) | 0.0428 (6) | −0.0048 (6) | 0.0294 (6) | −0.0059 (6) |
C1—C6 | 1.3820 (19) | N10—H10 | 0.900 (17) |
C1—C2 | 1.386 (2) | C11—C12 | 1.3829 (19) |
C1—N7 | 1.4058 (19) | C11—C16 | 1.392 (2) |
C2—C3 | 1.380 (2) | C12—C13 | 1.386 (2) |
C2—H2 | 0.93 | C12—H12 | 0.93 |
C3—C4 | 1.369 (2) | C13—C14 | 1.374 (2) |
C3—H3 | 0.93 | C13—H13 | 0.93 |
C4—C5 | 1.381 (2) | C14—C15 | 1.386 (2) |
C4—H4 | 0.93 | C14—H14 | 0.93 |
C5—C6 | 1.380 (2) | C15—C16 | 1.379 (2) |
C5—H5 | 0.93 | C15—C17 | 1.505 (2) |
C6—H6 | 0.93 | C16—H16 | 0.93 |
N7—C8 | 1.3678 (19) | C17—O18 | 1.421 (2) |
N7—H7 | 0.866 (17) | C17—H17A | 0.97 |
C8—O9 | 1.2291 (15) | C17—H17B | 0.97 |
C8—N10 | 1.3597 (18) | O18—H18 | 0.86 (2) |
N10—C11 | 1.4094 (18) | ||
C6—C1—C2 | 118.88 (14) | C11—N10—H10 | 115.1 (10) |
C6—C1—N7 | 124.41 (14) | C12—C11—C16 | 119.05 (14) |
C2—C1—N7 | 116.66 (12) | C12—C11—N10 | 124.67 (13) |
C3—C2—C1 | 120.73 (14) | C16—C11—N10 | 116.28 (12) |
C3—C2—H2 | 119.6 | C11—C12—C13 | 119.26 (14) |
C1—C2—H2 | 119.6 | C11—C12—H12 | 120.4 |
C4—C3—C2 | 120.39 (16) | C13—C12—H12 | 120.4 |
C4—C3—H3 | 119.8 | C14—C13—C12 | 121.38 (14) |
C2—C3—H3 | 119.8 | C14—C13—H13 | 119.3 |
C3—C4—C5 | 119.08 (15) | C12—C13—H13 | 119.3 |
C3—C4—H4 | 120.5 | C13—C14—C15 | 119.84 (15) |
C5—C4—H4 | 120.5 | C13—C14—H14 | 120.1 |
C6—C5—C4 | 121.08 (15) | C15—C14—H14 | 120.1 |
C6—C5—H5 | 119.5 | C16—C15—C14 | 118.90 (14) |
C4—C5—H5 | 119.5 | C16—C15—C17 | 119.96 (13) |
C5—C6—C1 | 119.84 (15) | C14—C15—C17 | 121.13 (14) |
C5—C6—H6 | 120.1 | C15—C16—C11 | 121.56 (13) |
C1—C6—H6 | 120.1 | C15—C16—H16 | 119.2 |
C8—N7—C1 | 127.08 (12) | C11—C16—H16 | 119.2 |
C8—N7—H7 | 115.2 (10) | O18—C17—C15 | 113.44 (13) |
C1—N7—H7 | 116.0 (10) | O18—C17—H17A | 108.9 |
O9—C8—N10 | 124.20 (14) | C15—C17—H17A | 108.9 |
O9—C8—N7 | 123.29 (13) | O18—C17—H17B | 108.9 |
N10—C8—N7 | 112.51 (12) | C15—C17—H17B | 108.9 |
C8—N10—C11 | 128.77 (12) | H17A—C17—H17B | 107.7 |
C8—N10—H10 | 115.9 (10) | C17—O18—H18 | 106.6 (14) |
D—H···A | D—H | H···A | D···A | D—H···A |
N7—H7···O18i | 0.87 (2) | 2.12 (2) | 2.958 (2) | 163 (1) |
N10—H10···O18i | 0.90 (2) | 2.18 (2) | 3.031 (2) | 157 (1) |
O18—H18···O9ii | 0.86 (2) | 1.91 (2) | 2.763 (2) | 175 (2) |
Symmetry codes: (i) −x+1, −y+1, −z; (ii) −x+1, y+1/2, −z+1/2. |
Experimental details
Crystal data | |
Chemical formula | C14H14N2O2 |
Mr | 242.27 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 296 |
a, b, c (Å) | 14.6207 (8), 7.0692 (4), 12.4019 (5) |
β (°) | 109.818 (3) |
V (Å3) | 1205.90 (11) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.22 × 0.21 × 0.05 |
Data collection | |
Diffractometer | Bruker SMART CCD area-detector diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 9960, 2694, 1664 |
Rint | 0.052 |
(sin θ/λ)max (Å−1) | 0.650 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.041, 0.111, 0.93 |
No. of reflections | 2694 |
No. of parameters | 175 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.14, −0.21 |
Computer programs: SMART (Bruker, 2002), SAINT (Bruker, 2002), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999).
D—H···A | D—H | H···A | D···A | D—H···A |
N7—H7···O18i | 0.87 (2) | 2.12 (2) | 2.958 (2) | 163 (1) |
N10—H10···O18i | 0.90 (2) | 2.18 (2) | 3.031 (2) | 157 (1) |
O18—H18···O9ii | 0.86 (2) | 1.91 (2) | 2.763 (2) | 175 (2) |
Symmetry codes: (i) −x+1, −y+1, −z; (ii) −x+1, y+1/2, −z+1/2. |
Acknowledgements
This work was undertaked 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). Also, we wish to thank the DBIO company for partial support of this work.
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This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
Melanin plays a major role in human skin protection as well as in undesirable browning of fruits and vegetables (Kubo et al., 2000). Tyrosinase is a key enzyme involved in the first stage of melanin synthesis. Tyrosinase catalyses two distinct reactions involving molecular oxygen, the hydroxylation of tyrosine to L-DOPA as a monophenolase and the oxidation of L-DOPA to dopaquinone as a diphenolase. Dopaquinone is non-enzymatically converted into dopachrome and dihydroxyindols, which induce the production of melanin pigments (Claus & Decker, 2006). Tyrosinase inhibitors have become increasingly important in both agriculture cosmetic industry and medication due to decreasing the excessive accumulation of pigmentation resulting from the enzyme action (Khan et al., 2006). 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 (Casañola-Martin et al., 2006) and tropolone (Son et al., 2000). They contain aromatic, methoxy, hydroxyl (Hong et al., 2008; Lee et al., 2007), aldehyde (Yi et al., 2010), and amide (Choi et al., 2010) groups in their structure. Nevertheless, 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. Therefore, it is still necessary to search and develop novel tyrosinase inhibitors with potent activities and lower side effects. In our continuing search for tyrosinase inhibitors, we have synthesized the title compound, (I), from the reaction of 3-aminobenzyl alcohol and phenyl isocyanate under ambient condition. Here, the crystal sturucture of (I) is described (Fig.1).
The 3-hydroxymethylphenyl moiety is essentially planar with a mean deviation of 0.010 Å from the corresponding least-squares plane defined by the eight constituent atoms. The dihedral angle between the benzene rings is 23.6 (1) °. The presence of intermolecular N—H···O and O—H···O hydrogen bonds link the molecules into a three-dimensional network (Fig. 2, Table 1). The H atoms of the NH groups of urea are positioned syn to each other.