Issue contents
Download PDF of article
Download CIF
3D view
Navigation
Highlighting
Dictionary of Crystallography reference
IUPAC Gold Book reference
more ...
Download citation
FormatBIBTeX
EndNote
RefMan
Refer
Medline
CIF
SGML
Plain Text
share
Previous article
Next article
Previous article
Issue contents
Download PDF of article
Download CIF
3D view
Navigation
Highlighting
Dictionary of Crystallography reference
IUPAC Gold Book reference
more ...
Download citation
FormatBIBTeX
EndNote
RefMan
Refer
Medline
CIF
SGML
Plain Text
share
Next article

organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 70| Part 3| March 2014| Page o278
doi:10.1107/S1600536814002773

4-Hy­dr­oxy-3-meth­­oxy­benzaldehyde 4-phenyl­thio­semicarbazone

Adriano Bof de Oliveira,a* Bárbara Regina Santos Feitosa,a Christian Nätherb and Inke Jessb

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

(Received 5 February 2014; accepted 6 February 2014; online 12 February 2014)

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[Lovejoy, D. & Richardson, D. R. (2008). The development of iron chelators for the treatment of cancer - Aroylhydrazone and thiosemicarbazone chelators for cancer treatment, pp. 1-117. Köln, Germany: Lambert Academic Publishing AG & Co. KG.]). For one of the first reports on the synthesis of thio­semicarbazone derivatives, see: Freund & Schander (1902[Freund, M. & Schander, A. (1902). Chem. Ber. 35, 2602-2606.]).

[Scheme 1]

Experimental

Crystal data

  • C15H15N3O2S

  • Mr = 301.36

  • Monoclinic, P 21 /c

  • a = 11.1010 (5) Å

  • b = 8.7279 (4) Å

  • c = 15.7921 (7) Å

  • β = 105.008 (4)°

  • V = 1477.88 (12) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.23 mm−1

  • T = 200 K

  • 0.3 × 0.2 × 0.15 mm
Data collection

  • Stoe IPDS-1 diffractometer

  • 7883 measured reflections

  • 2814 independent reflections

  • 2401 reflections with I > 2σ(I)

  • Rint = 0.050
Refinement

  • R[F2 > 2σ(F2)] = 0.034

  • wR(F2) = 0.083

  • S = 1.04

  • 2814 reflections

  • 193 parameters

  • H-atom parameters constrained

  • Δρmax = 0.22 e Å−3

  • Δρmin = −0.18 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

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+{\script{1\over 2}}, z-{\script{1\over 2}}]; (ii) -x+1, -y, -z+1; (iii) -x, -y+1, -z+1.

Data collection: X-AREA (Stoe & Cie, 2008[Stoe & Cie (2008). X-AREA, X-RED32 and X-SHAPE. Stoe & Cie, Darmstadt, Germany.]); cell refinement: X-AREA; data reduction: X-RED32 (Stoe & Cie, 2008[Stoe & Cie (2008). X-AREA, X-RED32 and X-SHAPE. Stoe & Cie, Darmstadt, Germany.]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: DIAMOND (Brandenburg, 2006[Brandenburg, K. (2006). DIAMOND. Crystal Impact GbR, Bonn, Germany.]); software used to prepare material for publication: publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Supporting information

CCDC reference: 985574

Crystal structure: contains datablocks I, publication_text. DOI: 10.1107/S1600536814002773/bt6961sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536814002773/bt6961Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536814002773/bt6961Isup3.cml

checkCIF report


Comment top

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).

Related literature top

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 top

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.

Refinement top

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.

Computing details top

Data collection: X-AREA (Stoe & Cie, 2008); cell refinement: 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).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound with labeling and displacement ellipsoids drawn at the 40% probability level.
[Figure 2] 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.
3-[(4-Hydroxy-3-methoxybenzylidene)amino]-1-phenylthiourea top
Crystal data top
C15H15N3O2SF(000) = 632
Mr = 301.36Dx = 1.354 Mg m−3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 2916 reflections
a = 11.1010 (5) Åθ = 1.9–26.0°
b = 8.7279 (4) ŵ = 0.23 mm−1
c = 15.7921 (7) ÅT = 200 K
β = 105.008 (4)°Plate, yellow
V = 1477.88 (12) Å30.3 × 0.2 × 0.15 mm
Z = 4
Data collection top
Stoe IPDS-1
diffractometer		2401 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube, Stoe IPDS-1Rint = 0.050
Graphite monochromatorθmax = 26.0°, θmin = 1.9°
φ scansh = −13→13
7883 measured reflectionsk = −10→10
2814 independent reflectionsl = −19→16
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.034H-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 reflectionsΔρmax = 0.22 e Å−3
193 parametersΔρmin = −0.18 e Å−3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0051 (19)
Crystal data top
C15H15N3O2SV = 1477.88 (12) Å3
Mr = 301.36Z = 4
Monoclinic, P21/cMo Kα radiation
a = 11.1010 (5) ŵ = 0.23 mm−1
b = 8.7279 (4) ÅT = 200 K
c = 15.7921 (7) Å0.3 × 0.2 × 0.15 mm
β = 105.008 (4)°
Data collection top
Stoe IPDS-1
diffractometer		2401 reflections with I > 2σ(I)
7883 measured reflectionsRint = 0.050
2814 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0340 restraints
wR(F2) = 0.083H-atom parameters constrained
S = 1.04Δρmax = 0.22 e Å−3
2814 reflectionsΔρmin = −0.18 e Å−3
193 parameters
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.09380 (14)0.31502 (18)0.38433 (10)0.0277 (3)
C2−0.00285 (14)0.23811 (19)0.32665 (11)0.0312 (4)
H20.00980.13690.30850.037*
C3−0.11786 (14)0.30837 (19)0.29539 (11)0.0308 (4)
H3−0.18420.25430.25690.037*
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)
C60.07610 (14)0.46702 (18)0.40785 (10)0.0279 (3)
H60.14260.52090.44630.033*
O1−0.24864 (10)0.53058 (14)0.29167 (8)0.0384 (3)
H1O1−0.29570.47960.25130.058*
O2−0.06289 (10)0.68653 (13)0.39208 (8)0.0354 (3)
C70.03941 (16)0.7771 (2)0.43923 (13)0.0408 (4)
H7A0.07120.73530.49840.061*
H7B0.01160.88290.44300.061*
H7C0.10580.77540.40870.061*
C80.21140 (14)0.23577 (18)0.41893 (11)0.0298 (4)
H80.22540.14160.39280.036*
N10.29680 (11)0.28779 (15)0.48318 (9)0.0283 (3)
N20.40487 (11)0.20239 (15)0.50512 (9)0.0292 (3)
H1N20.41600.12760.47060.035*
C90.49347 (13)0.23299 (17)0.57920 (10)0.0262 (3)
S10.62845 (4)0.13258 (5)0.60149 (3)0.03137 (14)
N30.46941 (12)0.34351 (16)0.63052 (9)0.0319 (3)
H1N30.39550.38730.61590.038*
C100.55817 (14)0.39469 (17)0.70857 (11)0.0293 (4)
C110.55360 (17)0.3387 (3)0.78865 (12)0.0442 (5)
H110.49330.26390.79290.053*
C120.63836 (19)0.3927 (3)0.86368 (13)0.0574 (6)
H120.63700.35360.91960.069*
C130.72416 (17)0.5025 (3)0.85702 (14)0.0530 (6)
H130.78060.54080.90850.064*
C140.72884 (18)0.5569 (2)0.77684 (15)0.0501 (5)
H140.78900.63190.77270.060*
C150.64570 (16)0.5026 (2)0.70154 (13)0.0407 (4)
H150.64900.53950.64560.049*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0247 (7)0.0305 (8)0.0259 (8)0.0031 (6)0.0030 (6)0.0008 (6)
C20.0306 (8)0.0301 (8)0.0297 (9)0.0020 (6)0.0021 (7)−0.0022 (6)
C30.0257 (7)0.0330 (8)0.0285 (8)−0.0013 (6)−0.0025 (6)−0.0008 (7)
C40.0228 (7)0.0344 (8)0.0273 (8)0.0037 (6)0.0022 (6)0.0037 (6)
C50.0269 (7)0.0271 (8)0.0282 (8)0.0029 (6)0.0057 (6)0.0012 (6)
C60.0236 (7)0.0303 (8)0.0272 (8)0.0002 (6)0.0022 (6)−0.0011 (6)
O10.0251 (6)0.0409 (7)0.0421 (7)0.0077 (5)−0.0044 (5)−0.0037 (5)
O20.0308 (6)0.0288 (6)0.0421 (7)0.0050 (5)0.0011 (5)−0.0036 (5)
C70.0380 (9)0.0296 (8)0.0518 (12)−0.0023 (7)0.0061 (8)−0.0067 (8)
C80.0269 (7)0.0291 (8)0.0301 (9)0.0040 (6)0.0014 (7)−0.0020 (6)
N10.0238 (6)0.0286 (7)0.0295 (7)0.0053 (5)0.0017 (5)0.0014 (5)
N20.0243 (6)0.0300 (7)0.0292 (7)0.0068 (5)−0.0002 (5)−0.0053 (6)
C90.0245 (7)0.0266 (7)0.0253 (8)0.0002 (6)0.0025 (6)−0.0005 (6)
S10.0239 (2)0.0357 (2)0.0300 (2)0.00726 (16)−0.00104 (15)−0.00724 (17)
N30.0249 (6)0.0327 (7)0.0334 (8)0.0063 (5)−0.0010 (6)−0.0083 (6)
C100.0263 (7)0.0275 (8)0.0315 (9)0.0047 (6)0.0029 (6)−0.0075 (6)
C110.0332 (9)0.0618 (12)0.0379 (10)−0.0056 (8)0.0099 (8)−0.0032 (9)
C120.0436 (11)0.0995 (18)0.0290 (10)0.0041 (12)0.0093 (9)−0.0088 (11)
C130.0331 (9)0.0692 (14)0.0500 (13)0.0050 (9)−0.0013 (9)−0.0333 (11)
C140.0405 (10)0.0360 (10)0.0659 (14)−0.0051 (8)−0.0002 (10)−0.0125 (9)
C150.0405 (9)0.0313 (9)0.0461 (11)−0.0028 (7)0.0034 (8)0.0023 (8)
Geometric parameters (Å, º) top
C1—C21.387 (2)N1—N21.3783 (17)
C1—C61.405 (2)N2—C91.3458 (19)
C1—C81.453 (2)N2—H1N20.8800
C2—C31.387 (2)C9—N31.331 (2)
C2—H20.9500C9—S11.6924 (15)
C3—C41.383 (2)N3—C101.4356 (19)
C3—H30.9500N3—H1N30.8800
C4—O11.3710 (18)C10—C111.369 (3)
C4—C51.406 (2)C10—C151.378 (2)
C5—O21.3645 (19)C11—C121.390 (3)
C5—C61.380 (2)C11—H110.9500
C6—H60.9500C12—C131.375 (3)
O1—H1O10.8400C12—H120.9500
O2—C71.425 (2)C13—C141.366 (3)
C7—H7A0.9800C13—H130.9500
C7—H7B0.9800C14—C151.386 (3)
C7—H7C0.9800C14—H140.9500
C8—N11.2792 (19)C15—H150.9500
C8—H80.9500
C2—C1—C6119.54 (14)C8—N1—N2115.18 (13)
C2—C1—C8118.90 (14)C9—N2—N1120.24 (13)
C6—C1—C8121.57 (14)C9—N2—H1N2119.9
C3—C2—C1120.26 (15)N1—N2—H1N2119.9
C3—C2—H2119.9N3—C9—N2117.17 (13)
C1—C2—H2119.9N3—C9—S1123.73 (11)
C4—C3—C2120.26 (14)N2—C9—S1119.10 (12)
C4—C3—H3119.9C9—N3—C10123.17 (13)
C2—C3—H3119.9C9—N3—H1N3118.4
O1—C4—C3122.45 (14)C10—N3—H1N3118.4
O1—C4—C5117.57 (14)C11—C10—C15120.93 (16)
C3—C4—C5119.98 (14)C11—C10—N3120.05 (15)
O2—C5—C6124.74 (14)C15—C10—N3119.01 (16)
O2—C5—C4115.64 (13)C10—C11—C12119.19 (19)
C6—C5—C4119.62 (14)C10—C11—H11120.4
C5—C6—C1120.26 (14)C12—C11—H11120.4
C5—C6—H6119.9C13—C12—C11120.0 (2)
C1—C6—H6119.9C13—C12—H12120.0
C4—O1—H1O1109.5C11—C12—H12120.0
C5—O2—C7116.78 (12)C14—C13—C12120.46 (18)
O2—C7—H7A109.5C14—C13—H13119.8
O2—C7—H7B109.5C12—C13—H13119.8
H7A—C7—H7B109.5C13—C14—C15119.98 (19)
O2—C7—H7C109.5C13—C14—H14120.0
H7A—C7—H7C109.5C15—C14—H14120.0
H7B—C7—H7C109.5C10—C15—C14119.41 (19)
N1—C8—C1122.57 (15)C10—C15—H15120.3
N1—C8—H8118.7C14—C15—H15120.3
C1—C8—H8118.7
C6—C1—C2—C3−2.8 (3)C1—C8—N1—N2−177.00 (14)
C8—C1—C2—C3177.29 (16)C8—N1—N2—C9−170.17 (15)
C1—C2—C3—C41.4 (3)N1—N2—C9—N32.5 (2)
C2—C3—C4—O1−179.19 (16)N1—N2—C9—S1−176.66 (11)
C2—C3—C4—C51.4 (3)N2—C9—N3—C10−176.04 (15)
O1—C4—C5—O2−2.8 (2)S1—C9—N3—C103.1 (2)
C3—C4—C5—O2176.67 (15)C9—N3—C10—C11−97.2 (2)
O1—C4—C5—C6177.76 (15)C9—N3—C10—C1584.1 (2)
C3—C4—C5—C6−2.8 (2)C15—C10—C11—C120.3 (3)
O2—C5—C6—C1−178.00 (16)N3—C10—C11—C12−178.35 (17)
C4—C5—C6—C11.4 (2)C10—C11—C12—C131.0 (3)
C2—C1—C6—C51.4 (2)C11—C12—C13—C14−1.5 (3)
C8—C1—C6—C5−178.71 (16)C12—C13—C14—C150.8 (3)
C6—C5—O2—C76.7 (2)C11—C10—C15—C14−1.1 (3)
C4—C5—O2—C7−172.72 (15)N3—C10—C15—C14177.63 (16)
C2—C1—C8—N1−167.58 (16)C13—C14—C15—C100.5 (3)
C6—C1—C8—N112.5 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1O1···S1i0.842.503.2844 (13)157
N2—H1N2···S1ii0.882.533.3460 (14)155
N3—H1N3···O1iii0.882.563.2068 (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.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1O1···S1i0.842.503.2844 (13)156.6
N2—H1N2···S1ii0.882.533.3460 (14)154.5
N3—H1N3···O1iii0.882.563.2068 (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

First citationBrandenburg, K. (2006). DIAMOND. Crystal Impact GbR, Bonn, Germany.  Google Scholar
 First citationFreund, M. & Schander, A. (1902). Chem. Ber. 35, 2602–2606.  CrossRef CAS Google Scholar
 First citationLovejoy, D. & Richardson, D. R. (2008). The development of iron chelators for the treatment of cancer - Aroylhydrazone and thiosemicarbazone chelators for cancer treatment, pp. 1–117. Köln, Germany: Lambert Academic Publishing AG & Co. KG.  Google Scholar
 First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationStoe & Cie (2008). X-AREA, X-RED32 and X-SHAPE. Stoe & Cie, Darmstadt, Germany.  Google Scholar
 First citationWestrip, S. P. (2010). J. Appl. Cryst. 43, 920–925.  Web of Science CrossRef CAS IUCr Journals Google Scholar

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.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 70| Part 3| March 2014| Page o278
doi:10.1107/S1600536814002773
Follow Acta Cryst. E
Sign up for e-alerts
E-alerts
Follow Acta Cryst. on Twitter
Twitter
Follow us on facebook
Facebook
Sign up for RSS feeds
RSS