4-Hydroxy-3-methoxybenzaldehyde 4-ethylthiosemicarbazone

In the crystal structure of the title compound, C11H15N3O2S, the C—N—N—C and C—N—C—C torsion angles involving the benzene ring and ethyl group are 11.91 (15) and 99.4 (2)°, respectively. An intramolecular N—H⋯N hydrogen bond is observed. In the crystal, molecules are linked via N—H⋯O and N—H⋯S hydrogen bonds into a three-dimensional hydrogen bonded network. Finally, the molecules show a herringbone arrangement when viewed along the a axis.


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).

S2. Comment
Thiosemicarbazone derivatives have a wide range of biological properties. For example, some thiosemicarbazones show anti-proliferative activity against tumor cells (Lovejoy & Richardson, 2008). As part of our study on synthesis and structural chemistry of thiosemicarbazone derivatives from natural products, we report herein the crystal structure of a derivative of vanillin.
In the title compound, C 11 H 15 N 3 O 2 S, Fig. 1, the C-N-N-C and C-N-C-C fragments makes torsion angles of 11.91 (15)° and 99.4 (2)° with the benzene ring and ethyl group respectively. The molecule matches the asymmetric unit ( Fig. 1) and shows a trans conformation at the C7-N1 and N1-N2 bonds. In the crystal structure the molecules are linked via N-H···O and O-H···S hydrogen bonds interactions into a crystal packing which shows a herringbone arrangement viewed along the a-axis, Fig.2. Additionally, one N-H···N intramolecular hydrogen bond interactions is observed, Table 1,

S3. Experimental
Starting materials were commercially available and were used without further purification. The synthesis of the title compound was adapted to a procedure reported previously (Freund & Schander, 1902). In a hydrochloric acid catalyzed reaction, a mixture of vanillin (10 mmol) and 4-ethyl-3-thiosemicarbazide (10 mmol) in ethanol (80 ml), was refluxed for 5 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.

S4. Refinement
All hydrogen atoms were localized in a difference density Fourier map. Their positions and isotropic displacement parameters were refined.  The molecular structure of the title compound with labeling and displacement ellipsoids drawn at the 50% probability level.

Figure 2
Crystal structure of the title compound viewed along the b-axis. The herringbone pattern of the crystal packing along the a-axis is observed. KappaCCD Graphite monochromator Detector resolution: 9 pixels mm -1 CCD rotation images, thick slices scans Absorption correction: multi-scan (Blessing, 1995) T 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.