organic compounds
4-Hydroxy-3-methoxybenzaldehyde 4-phenylthiosemicarbazone
aDepartamento de Química, Universidade Federal de Sergipe, Av. Marechal Rondon s/n, Campus, 49100-000 São Cristóvão, SE, Brazil, and bInstitut für Anorganische Chemie, Christian-Albrechts-Universität zu Kiel, Max-Eyth Strasse 2, D-24118 Kiel, Germany
*Correspondence e-mail: adriano@daad-alumni.de
In the title compound, C15H15N3O2S, the central C—N—N—C unit has an anti conformation [torsion angle = −170.17 (15)°]. The phenyl substituent is oriented perpendicular to this unit [dihedral angle of 89.2 (1)°], whereas the substituted ring is rotated out of this plane by only 18.86 (17)°. In the crystal, molecules are linked by pairs of N—H⋯S hydrogen bonds into inversion dimers that are further connected via N—H⋯O and O—H⋯S hydrogen bonds into a three-dimensional network.
CCDC reference: 985574
Related literature
For the synthesis and biological applications of thiosemicarbazone derivatives, see: Lovejoy & Richardson (2008). For one of the first reports on the synthesis of thiosemicarbazone derivatives, see: Freund & Schander (1902).
Experimental
Crystal data
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Data collection: X-AREA (Stoe & Cie, 2008); cell X-AREA; data reduction: X-RED32 (Stoe & Cie, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg, 2006); software used to prepare material for publication: publCIF (Westrip, 2010).
Supporting information
CCDC reference: 985574
10.1107/S1600536814002773/bt6961sup1.cif
contains datablocks I, publication_text. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536814002773/bt6961Isup2.hkl
Supporting information file. DOI: 10.1107/S1600536814002773/bt6961Isup3.cml
Starting materials were commercially available and were used without further purification. The title compound synthesis was adapted from a procedure reported previously (Freund & Schander, 1902). The hydrochloric acid catalyzed reaction of vanillin (8,83 mmol) and 4-phenylthiosemicarbazide (8,83 mmol) in ethanol (50 ml) was refluxed for 6 h. After cooling and filtering, the title compound was obtained. Crystals suitable for X-ray diffraction were obtained in ethanol by the slow evaporation of solvent.
All non-hydrogen atoms were refined anisotropic. All H atoms were located in difference map but were positioned with idealized geometry (methyl and O—H H atoms allowed to rotate but no to tip) and were refined isotropic with Uiso(H) = 1.2 Ueq(C, N,O) (1.5 for methyl and O—H H atoms) using a riding model with C—H = 0.95 Å for aromatic, C—H = 0.98 Å for methyl, N—H = 0.88 Å for amine and hydrazine O—H = 0.84 Å for hydroxyl H atoms.
Data collection: X-AREA (Stoe & Cie, 2008); cell
X-AREA (Stoe & Cie, 2008); data reduction: X-RED32 (Stoe & Cie, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg, 2006); software used to prepare material for publication: publCIF (Westrip, 2010).Fig. 1. The molecular structure of the title compound with labeling and displacement ellipsoids drawn at the 40% probability level. | |
Fig. 2. Part of the crystal structure of the title compound with view along the crystallographic c-axis. Intermolecular hydrogen bonding is shown as dashed lines. |
C15H15N3O2S | F(000) = 632 |
Mr = 301.36 | Dx = 1.354 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ybc | Cell parameters from 2916 reflections |
a = 11.1010 (5) Å | θ = 1.9–26.0° |
b = 8.7279 (4) Å | µ = 0.23 mm−1 |
c = 15.7921 (7) Å | T = 200 K |
β = 105.008 (4)° | Plate, yellow |
V = 1477.88 (12) Å3 | 0.3 × 0.2 × 0.15 mm |
Z = 4 |
Stoe IPDS-1 diffractometer | 2401 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube, Stoe IPDS-1 | Rint = 0.050 |
Graphite monochromator | θmax = 26.0°, θmin = 1.9° |
φ scans | h = −13→13 |
7883 measured reflections | k = −10→10 |
2814 independent reflections | l = −19→16 |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.034 | H-atom parameters constrained |
wR(F2) = 0.083 | w = 1/[σ2(Fo2) + (0.0283P)2 + 0.5666P] where P = (Fo2 + 2Fc2)/3 |
S = 1.04 | (Δ/σ)max = 0.001 |
2814 reflections | Δρmax = 0.22 e Å−3 |
193 parameters | Δρmin = −0.18 e Å−3 |
0 restraints | Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0051 (19) |
C15H15N3O2S | V = 1477.88 (12) Å3 |
Mr = 301.36 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 11.1010 (5) Å | µ = 0.23 mm−1 |
b = 8.7279 (4) Å | T = 200 K |
c = 15.7921 (7) Å | 0.3 × 0.2 × 0.15 mm |
β = 105.008 (4)° |
Stoe IPDS-1 diffractometer | 2401 reflections with I > 2σ(I) |
7883 measured reflections | Rint = 0.050 |
2814 independent reflections |
R[F2 > 2σ(F2)] = 0.034 | 0 restraints |
wR(F2) = 0.083 | H-atom parameters constrained |
S = 1.04 | Δρmax = 0.22 e Å−3 |
2814 reflections | Δρmin = −0.18 e Å−3 |
193 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. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.09380 (14) | 0.31502 (18) | 0.38433 (10) | 0.0277 (3) | |
C2 | −0.00285 (14) | 0.23811 (19) | 0.32665 (11) | 0.0312 (4) | |
H2 | 0.0098 | 0.1369 | 0.3085 | 0.037* | |
C3 | −0.11786 (14) | 0.30837 (19) | 0.29539 (11) | 0.0308 (4) | |
H3 | −0.1842 | 0.2543 | 0.2569 | 0.037* | |
C4 | −0.13632 (14) | 0.45689 (19) | 0.31995 (10) | 0.0289 (3) | |
C5 | −0.03748 (14) | 0.53832 (18) | 0.37529 (10) | 0.0277 (3) | |
C6 | 0.07610 (14) | 0.46702 (18) | 0.40785 (10) | 0.0279 (3) | |
H6 | 0.1426 | 0.5209 | 0.4463 | 0.033* | |
O1 | −0.24864 (10) | 0.53058 (14) | 0.29167 (8) | 0.0384 (3) | |
H1O1 | −0.2957 | 0.4796 | 0.2513 | 0.058* | |
O2 | −0.06289 (10) | 0.68653 (13) | 0.39208 (8) | 0.0354 (3) | |
C7 | 0.03941 (16) | 0.7771 (2) | 0.43923 (13) | 0.0408 (4) | |
H7A | 0.0712 | 0.7353 | 0.4984 | 0.061* | |
H7B | 0.0116 | 0.8829 | 0.4430 | 0.061* | |
H7C | 0.1058 | 0.7754 | 0.4087 | 0.061* | |
C8 | 0.21140 (14) | 0.23577 (18) | 0.41893 (11) | 0.0298 (4) | |
H8 | 0.2254 | 0.1416 | 0.3928 | 0.036* | |
N1 | 0.29680 (11) | 0.28779 (15) | 0.48318 (9) | 0.0283 (3) | |
N2 | 0.40487 (11) | 0.20239 (15) | 0.50512 (9) | 0.0292 (3) | |
H1N2 | 0.4160 | 0.1276 | 0.4706 | 0.035* | |
C9 | 0.49347 (13) | 0.23299 (17) | 0.57920 (10) | 0.0262 (3) | |
S1 | 0.62845 (4) | 0.13258 (5) | 0.60149 (3) | 0.03137 (14) | |
N3 | 0.46941 (12) | 0.34351 (16) | 0.63052 (9) | 0.0319 (3) | |
H1N3 | 0.3955 | 0.3873 | 0.6159 | 0.038* | |
C10 | 0.55817 (14) | 0.39469 (17) | 0.70857 (11) | 0.0293 (4) | |
C11 | 0.55360 (17) | 0.3387 (3) | 0.78865 (12) | 0.0442 (5) | |
H11 | 0.4933 | 0.2639 | 0.7929 | 0.053* | |
C12 | 0.63836 (19) | 0.3927 (3) | 0.86368 (13) | 0.0574 (6) | |
H12 | 0.6370 | 0.3536 | 0.9196 | 0.069* | |
C13 | 0.72416 (17) | 0.5025 (3) | 0.85702 (14) | 0.0530 (6) | |
H13 | 0.7806 | 0.5408 | 0.9085 | 0.064* | |
C14 | 0.72884 (18) | 0.5569 (2) | 0.77684 (15) | 0.0501 (5) | |
H14 | 0.7890 | 0.6319 | 0.7727 | 0.060* | |
C15 | 0.64570 (16) | 0.5026 (2) | 0.70154 (13) | 0.0407 (4) | |
H15 | 0.6490 | 0.5395 | 0.6456 | 0.049* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0247 (7) | 0.0305 (8) | 0.0259 (8) | 0.0031 (6) | 0.0030 (6) | 0.0008 (6) |
C2 | 0.0306 (8) | 0.0301 (8) | 0.0297 (9) | 0.0020 (6) | 0.0021 (7) | −0.0022 (6) |
C3 | 0.0257 (7) | 0.0330 (8) | 0.0285 (8) | −0.0013 (6) | −0.0025 (6) | −0.0008 (7) |
C4 | 0.0228 (7) | 0.0344 (8) | 0.0273 (8) | 0.0037 (6) | 0.0022 (6) | 0.0037 (6) |
C5 | 0.0269 (7) | 0.0271 (8) | 0.0282 (8) | 0.0029 (6) | 0.0057 (6) | 0.0012 (6) |
C6 | 0.0236 (7) | 0.0303 (8) | 0.0272 (8) | 0.0002 (6) | 0.0022 (6) | −0.0011 (6) |
O1 | 0.0251 (6) | 0.0409 (7) | 0.0421 (7) | 0.0077 (5) | −0.0044 (5) | −0.0037 (5) |
O2 | 0.0308 (6) | 0.0288 (6) | 0.0421 (7) | 0.0050 (5) | 0.0011 (5) | −0.0036 (5) |
C7 | 0.0380 (9) | 0.0296 (8) | 0.0518 (12) | −0.0023 (7) | 0.0061 (8) | −0.0067 (8) |
C8 | 0.0269 (7) | 0.0291 (8) | 0.0301 (9) | 0.0040 (6) | 0.0014 (7) | −0.0020 (6) |
N1 | 0.0238 (6) | 0.0286 (7) | 0.0295 (7) | 0.0053 (5) | 0.0017 (5) | 0.0014 (5) |
N2 | 0.0243 (6) | 0.0300 (7) | 0.0292 (7) | 0.0068 (5) | −0.0002 (5) | −0.0053 (6) |
C9 | 0.0245 (7) | 0.0266 (7) | 0.0253 (8) | 0.0002 (6) | 0.0025 (6) | −0.0005 (6) |
S1 | 0.0239 (2) | 0.0357 (2) | 0.0300 (2) | 0.00726 (16) | −0.00104 (15) | −0.00724 (17) |
N3 | 0.0249 (6) | 0.0327 (7) | 0.0334 (8) | 0.0063 (5) | −0.0010 (6) | −0.0083 (6) |
C10 | 0.0263 (7) | 0.0275 (8) | 0.0315 (9) | 0.0047 (6) | 0.0029 (6) | −0.0075 (6) |
C11 | 0.0332 (9) | 0.0618 (12) | 0.0379 (10) | −0.0056 (8) | 0.0099 (8) | −0.0032 (9) |
C12 | 0.0436 (11) | 0.0995 (18) | 0.0290 (10) | 0.0041 (12) | 0.0093 (9) | −0.0088 (11) |
C13 | 0.0331 (9) | 0.0692 (14) | 0.0500 (13) | 0.0050 (9) | −0.0013 (9) | −0.0333 (11) |
C14 | 0.0405 (10) | 0.0360 (10) | 0.0659 (14) | −0.0051 (8) | −0.0002 (10) | −0.0125 (9) |
C15 | 0.0405 (9) | 0.0313 (9) | 0.0461 (11) | −0.0028 (7) | 0.0034 (8) | 0.0023 (8) |
C1—C2 | 1.387 (2) | N1—N2 | 1.3783 (17) |
C1—C6 | 1.405 (2) | N2—C9 | 1.3458 (19) |
C1—C8 | 1.453 (2) | N2—H1N2 | 0.8800 |
C2—C3 | 1.387 (2) | C9—N3 | 1.331 (2) |
C2—H2 | 0.9500 | C9—S1 | 1.6924 (15) |
C3—C4 | 1.383 (2) | N3—C10 | 1.4356 (19) |
C3—H3 | 0.9500 | N3—H1N3 | 0.8800 |
C4—O1 | 1.3710 (18) | C10—C11 | 1.369 (3) |
C4—C5 | 1.406 (2) | C10—C15 | 1.378 (2) |
C5—O2 | 1.3645 (19) | C11—C12 | 1.390 (3) |
C5—C6 | 1.380 (2) | C11—H11 | 0.9500 |
C6—H6 | 0.9500 | C12—C13 | 1.375 (3) |
O1—H1O1 | 0.8400 | C12—H12 | 0.9500 |
O2—C7 | 1.425 (2) | C13—C14 | 1.366 (3) |
C7—H7A | 0.9800 | C13—H13 | 0.9500 |
C7—H7B | 0.9800 | C14—C15 | 1.386 (3) |
C7—H7C | 0.9800 | C14—H14 | 0.9500 |
C8—N1 | 1.2792 (19) | C15—H15 | 0.9500 |
C8—H8 | 0.9500 | ||
C2—C1—C6 | 119.54 (14) | C8—N1—N2 | 115.18 (13) |
C2—C1—C8 | 118.90 (14) | C9—N2—N1 | 120.24 (13) |
C6—C1—C8 | 121.57 (14) | C9—N2—H1N2 | 119.9 |
C3—C2—C1 | 120.26 (15) | N1—N2—H1N2 | 119.9 |
C3—C2—H2 | 119.9 | N3—C9—N2 | 117.17 (13) |
C1—C2—H2 | 119.9 | N3—C9—S1 | 123.73 (11) |
C4—C3—C2 | 120.26 (14) | N2—C9—S1 | 119.10 (12) |
C4—C3—H3 | 119.9 | C9—N3—C10 | 123.17 (13) |
C2—C3—H3 | 119.9 | C9—N3—H1N3 | 118.4 |
O1—C4—C3 | 122.45 (14) | C10—N3—H1N3 | 118.4 |
O1—C4—C5 | 117.57 (14) | C11—C10—C15 | 120.93 (16) |
C3—C4—C5 | 119.98 (14) | C11—C10—N3 | 120.05 (15) |
O2—C5—C6 | 124.74 (14) | C15—C10—N3 | 119.01 (16) |
O2—C5—C4 | 115.64 (13) | C10—C11—C12 | 119.19 (19) |
C6—C5—C4 | 119.62 (14) | C10—C11—H11 | 120.4 |
C5—C6—C1 | 120.26 (14) | C12—C11—H11 | 120.4 |
C5—C6—H6 | 119.9 | C13—C12—C11 | 120.0 (2) |
C1—C6—H6 | 119.9 | C13—C12—H12 | 120.0 |
C4—O1—H1O1 | 109.5 | C11—C12—H12 | 120.0 |
C5—O2—C7 | 116.78 (12) | C14—C13—C12 | 120.46 (18) |
O2—C7—H7A | 109.5 | C14—C13—H13 | 119.8 |
O2—C7—H7B | 109.5 | C12—C13—H13 | 119.8 |
H7A—C7—H7B | 109.5 | C13—C14—C15 | 119.98 (19) |
O2—C7—H7C | 109.5 | C13—C14—H14 | 120.0 |
H7A—C7—H7C | 109.5 | C15—C14—H14 | 120.0 |
H7B—C7—H7C | 109.5 | C10—C15—C14 | 119.41 (19) |
N1—C8—C1 | 122.57 (15) | C10—C15—H15 | 120.3 |
N1—C8—H8 | 118.7 | C14—C15—H15 | 120.3 |
C1—C8—H8 | 118.7 | ||
C6—C1—C2—C3 | −2.8 (3) | C1—C8—N1—N2 | −177.00 (14) |
C8—C1—C2—C3 | 177.29 (16) | C8—N1—N2—C9 | −170.17 (15) |
C1—C2—C3—C4 | 1.4 (3) | N1—N2—C9—N3 | 2.5 (2) |
C2—C3—C4—O1 | −179.19 (16) | N1—N2—C9—S1 | −176.66 (11) |
C2—C3—C4—C5 | 1.4 (3) | N2—C9—N3—C10 | −176.04 (15) |
O1—C4—C5—O2 | −2.8 (2) | S1—C9—N3—C10 | 3.1 (2) |
C3—C4—C5—O2 | 176.67 (15) | C9—N3—C10—C11 | −97.2 (2) |
O1—C4—C5—C6 | 177.76 (15) | C9—N3—C10—C15 | 84.1 (2) |
C3—C4—C5—C6 | −2.8 (2) | C15—C10—C11—C12 | 0.3 (3) |
O2—C5—C6—C1 | −178.00 (16) | N3—C10—C11—C12 | −178.35 (17) |
C4—C5—C6—C1 | 1.4 (2) | C10—C11—C12—C13 | 1.0 (3) |
C2—C1—C6—C5 | 1.4 (2) | C11—C12—C13—C14 | −1.5 (3) |
C8—C1—C6—C5 | −178.71 (16) | C12—C13—C14—C15 | 0.8 (3) |
C6—C5—O2—C7 | 6.7 (2) | C11—C10—C15—C14 | −1.1 (3) |
C4—C5—O2—C7 | −172.72 (15) | N3—C10—C15—C14 | 177.63 (16) |
C2—C1—C8—N1 | −167.58 (16) | C13—C14—C15—C10 | 0.5 (3) |
C6—C1—C8—N1 | 12.5 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1O1···S1i | 0.84 | 2.50 | 3.2844 (13) | 157 |
N2—H1N2···S1ii | 0.88 | 2.53 | 3.3460 (14) | 155 |
N3—H1N3···O1iii | 0.88 | 2.56 | 3.2068 (18) | 131 |
Symmetry codes: (i) x−1, −y+1/2, z−1/2; (ii) −x+1, −y, −z+1; (iii) −x, −y+1, −z+1. |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1O1···S1i | 0.84 | 2.50 | 3.2844 (13) | 156.6 |
N2—H1N2···S1ii | 0.88 | 2.53 | 3.3460 (14) | 154.5 |
N3—H1N3···O1iii | 0.88 | 2.56 | 3.2068 (18) | 131.4 |
Symmetry codes: (i) x−1, −y+1/2, z−1/2; (ii) −x+1, −y, −z+1; (iii) −x, −y+1, −z+1. |
Acknowledgements
We gratefully acknowledge financial support by the State of Schleswig–Holstein, Germany. We thank Professor Dr Wolfgang Bensch for access to his experimental facilities. BRSF thanks CNPq/UFS for the award of a PIBIC scholarship and ABO acknowledges financial support through the FAPITEC/SE/FUNTEC/CNPq PPP 04/2011 program.
References
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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.
The thiosemicarbazone chemistry has some impact on the search for new compounds used for the treatment of cancer. Thiosemicarbazone derivatives can act as ligands, e.g. with iron in the active centre of Fe-containing proteins and showing anti-proliferative activity against tumor cells (Lovejoy & Richardson, 2008). As part of our study on synthesis and structural chemistry of thiosemicarbazone derivatives, we report herein the crystal structure of a derivative of vanillin (4-Hydroxy-3-methoxybenzaldehyde).
In the crystal structure of the title compound the central CNNC unit is nearly planar with an torsion angle along C8—N1—N2—C9 of 170.17 (15)° and maximum deviations from the mean plane of 0.0542 (8) Å. The substituted phenyl ring (C1—C6) is slightly rotated out of this plane by 18.86 (17) °. In contrast, the unsubstituted phenyl ring (C10—C15) is perpendicular to the CNNC fragment with an dihedral angle of 89.2 (1)° (Fig. 1). The molecule shows a trans conformation about the C8—N1 and N1—N2 bonds.
In the crystal structure the molecules are linked by pairs of N—H···S hydrogen bonds into dimers that are located on centres of inversion (Fig. 2 and Table 1). These dimers are further linked by intermolecular N—H···O and O—H···S hydrogen bonding into a three-dimensional hydrogen bonded network (Fig. 2 and Table 1).