4-Hydroxy-3-methoxybenzaldehyde 4-phenylthiosemicarbazone

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.

In the title compound, C 15 H 15 N 3 O 2 S, the central C-N-N-C unit has an anti conformation [torsion angle = À170.17 (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-HÁ Á ÁS hydrogen bonds into inversion dimers that are further connected via N-HÁ Á ÁO and O-HÁ Á ÁS hydrogen bonds into a three-dimensional network.

Comment
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).

Experimental
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
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 U iso (  The molecular structure of the title compound with labeling and displacement ellipsoids drawn at the 40% probability level.

Figure 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.

Special details
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 F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.