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.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.030
• wR factor = 0.071
• Data-to-parameter ratio = 13.3

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT089_ALERT_3_C Poor Data / Parameter Ratio (Zmax < 18) ........       7.07 Note
PLAT420_ALERT_2_C D-H Without Acceptor       N2     -   HN2    ...     Please Check
PLAT790_ALERT_4_C Centre of Gravity not Within Unit Cell: Resd.  #          1 Note
              C11 H15 N3 O2 S

Alert level G
PLAT005_ALERT_5_G No _iucr_refine_instructions_details  in the CIF     Please Do !
PLAT199_ALERT_1_G Reported _cell_measurement_temperature ..... (K)        293 Check
PLAT200_ALERT_1_G Reported   _diffrn_ambient_temperature ..... (K)        293 Check
PLAT720_ALERT_4_G Number of Unusual/Non-Standard Labels ..........          3 Note
PLAT764_ALERT_4_G Overcomplete CIF Bond List Detected (Rep/Expd) .       1.12 Ratio
PLAT910_ALERT_3_G Missing # of FCF Reflections Below Th(Min) .....          3 Why ?

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   3 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   6 ALERT level G = General information/check it is not something unexpected

   2 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
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   3 ALERT type 4 Improvement, methodology, query or suggestion
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S1. Related Literature

For Biological activities of thio­semicarbazone derivatives see Lovejoy & Richardson, 2008.

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, C₁₁H₁₅N₃O₂S, 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,

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).

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.

Computing details

Data collection: COLLECT (Nonius, 1998); cell refinement: HKL SCALEPACK (Otwinowski & Minor, 1997); data reduction: HKL, DENZO and SCALEPACK (Otwinowski & Minor, 1997); 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

	Fig. 1. The molecular structure of the title compound with labeling and displacement ellipsoids drawn at the 50% probability level.
	Fig. 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.

4-Hydroxy-3-methoxybenzaldehyde 4-ethylthiosemicarbazone

Crystal data

C11H15N3O2S	F(000) = 536
Mr = 253.32	Dx = 1.358 Mg m^−3
Orthorhombic, Pna21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2c -2n	Cell parameters from 31793 reflections
a = 8.9962 (2) Å	θ = 2.9–27.5°
b = 16.1159 (2) Å	µ = 0.26 mm^−1
c = 8.5491 (1) Å	T = 293 K
V = 1239.46 (3) Å^3	Prism, yellow
Z = 4	0.15 × 0.13 × 0.12 mm

Data collection

Nonius Kappa CCD diffractometer	2837 independent reflections
Radiation source: fine-focus sealed tube, Nonius KappaCCD	2590 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.050
Detector resolution: 9 pixels mm^-1	θmax = 27.5°, θmin = 3.4°
CCD rotation images, thick slices scans	h = −11→11
Absorption correction: multi-scan (Blessing, 1995)	k = −20→20
Tmin = 0.939, Tmax = 0.990	l = −11→11
22619 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.030	All H-atom parameters refined
wR(F^2) = 0.071	w = 1/[σ^2(Fo^2) + (0.0355P)^2 + 0.3575P] where P = (Fo^2 + 2Fc^2)/3
S = 1.01	(Δ/σ)max < 0.001
2837 reflections	Δρmax = 0.15 e Å^−3
214 parameters	Δρmin = −0.23 e Å^−3
1 restraint	Absolute structure: Flack (1983), ???? Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.03 (6)

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 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 (Ų)

	x	y	z	Uiso*/Ueq
S1	−0.13718 (5)	−0.18485 (2)	−0.32559 (6)	0.02743 (12)
O1	0.63909 (13)	0.01577 (7)	−0.84398 (16)	0.0256 (3)
O2	0.77231 (14)	−0.08623 (8)	−1.02714 (15)	0.0254 (3)
N1	0.21760 (16)	−0.15200 (8)	−0.58307 (17)	0.0196 (3)
N2	0.10393 (16)	−0.18657 (9)	−0.49707 (18)	0.0212 (3)
N3	0.03634 (18)	−0.05684 (9)	−0.41867 (19)	0.0210 (3)
C1	0.42396 (18)	−0.17397 (10)	−0.7544 (2)	0.0189 (3)
C2	0.47154 (19)	−0.09078 (10)	−0.7448 (2)	0.0190 (3)
C3	0.58669 (18)	−0.06350 (9)	−0.8387 (2)	0.0195 (3)
C4	0.65784 (18)	−0.11894 (11)	−0.9413 (2)	0.0193 (3)
C5	0.61052 (19)	−0.20035 (11)	−0.9515 (2)	0.0211 (3)
C6	0.49352 (18)	−0.22780 (10)	−0.8580 (2)	0.0208 (3)
C7	0.29879 (19)	−0.20341 (11)	−0.6600 (2)	0.0199 (3)
C8	0.00811 (18)	−0.13729 (10)	−0.4166 (2)	0.0194 (3)
C9	−0.0612 (2)	0.00841 (10)	−0.3584 (2)	0.0242 (4)
C10	−0.1481 (2)	0.04899 (14)	−0.4896 (2)	0.0328 (4)
C11	0.5543 (2)	0.07826 (11)	−0.7660 (3)	0.0306 (4)
HO2	0.795 (3)	−0.1171 (16)	−1.105 (3)	0.052 (8)*
HN2	0.094 (2)	−0.2387 (13)	−0.487 (2)	0.019 (5)*
HN3	0.109 (2)	−0.0442 (13)	−0.461 (2)	0.022 (5)*
H2	0.425 (2)	−0.0549 (12)	−0.676 (2)	0.022 (5)*
H5	0.664 (2)	−0.2354 (12)	−1.029 (2)	0.021 (5)*
H6	0.461 (2)	−0.2851 (12)	−0.866 (2)	0.026 (5)*
H7	0.2793 (19)	−0.2637 (12)	−0.662 (2)	0.017 (4)*
H9A	0.008 (2)	0.0526 (12)	−0.307 (2)	0.023 (5)*
H9B	−0.129 (2)	−0.0134 (12)	−0.279 (2)	0.022 (5)*
H10A	−0.078 (3)	0.0751 (15)	−0.573 (3)	0.047 (7)*
H10B	−0.212 (2)	0.0056 (12)	−0.544 (3)	0.028 (5)*
H10C	−0.215 (3)	0.0921 (15)	−0.450 (3)	0.046 (6)*
H11A	0.604 (2)	0.1297 (13)	−0.788 (3)	0.032 (6)*
H11B	0.448 (3)	0.0771 (13)	−0.803 (3)	0.038 (6)*
H11C	0.553 (3)	0.0652 (14)	−0.645 (3)	0.045 (7)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0304 (2)	0.02365 (19)	0.0283 (2)	−0.00829 (17)	0.0134 (2)	−0.0068 (2)
O1	0.0267 (6)	0.0195 (5)	0.0305 (7)	−0.0043 (5)	0.0100 (6)	−0.0047 (6)
O2	0.0264 (6)	0.0264 (6)	0.0234 (7)	−0.0068 (5)	0.0098 (5)	−0.0045 (5)
N1	0.0187 (7)	0.0211 (7)	0.0190 (7)	−0.0021 (6)	0.0033 (6)	0.0017 (6)
N2	0.0221 (7)	0.0163 (7)	0.0253 (8)	−0.0019 (6)	0.0089 (6)	0.0004 (6)
N3	0.0207 (7)	0.0180 (7)	0.0244 (8)	−0.0002 (6)	0.0054 (6)	0.0001 (6)
C1	0.0183 (8)	0.0217 (8)	0.0168 (7)	0.0011 (6)	−0.0002 (7)	0.0038 (6)
C2	0.0181 (8)	0.0205 (8)	0.0182 (8)	0.0023 (6)	0.0014 (7)	−0.0012 (7)
C3	0.0207 (7)	0.0184 (7)	0.0192 (8)	−0.0006 (6)	−0.0001 (7)	0.0011 (7)
C4	0.0191 (8)	0.0235 (8)	0.0154 (7)	−0.0009 (6)	0.0022 (7)	0.0021 (6)
C5	0.0217 (8)	0.0217 (8)	0.0200 (9)	0.0020 (6)	0.0019 (7)	−0.0016 (7)
C6	0.0209 (8)	0.0188 (7)	0.0226 (8)	−0.0005 (6)	0.0008 (7)	0.0013 (7)
C7	0.0212 (8)	0.0202 (8)	0.0182 (8)	0.0006 (7)	0.0006 (7)	0.0013 (7)
C8	0.0208 (8)	0.0213 (8)	0.0162 (7)	−0.0021 (7)	0.0002 (7)	−0.0015 (7)
C9	0.0299 (9)	0.0190 (7)	0.0238 (9)	0.0026 (7)	0.0081 (8)	−0.0024 (7)
C10	0.0321 (10)	0.0347 (10)	0.0316 (10)	0.0121 (9)	0.0042 (9)	−0.0003 (9)
C11	0.0323 (11)	0.0192 (9)	0.0404 (12)	−0.0005 (8)	0.0100 (9)	−0.0054 (8)

Geometric parameters (Å, º)

S1—C8	1.7035 (17)	C2—H2	0.93 (2)
O1—C3	1.3625 (18)	C3—C4	1.406 (2)
O1—C11	1.429 (2)	C4—C5	1.382 (2)
O2—C4	1.370 (2)	C5—C6	1.394 (2)
O2—HO2	0.86 (3)	C5—H5	0.99 (2)
N1—C7	1.286 (2)	C6—H6	0.97 (2)
N1—N2	1.377 (2)	C7—N1	1.286 (2)
N2—C8	1.359 (2)	C7—H7	0.988 (18)
N2—N1	1.377 (2)	C9—C10	1.515 (3)
N2—HN2	0.85 (2)	C9—H9A	1.046 (19)
N3—C8	1.321 (2)	C9—H9B	0.98 (2)
N3—C9	1.463 (2)	C10—H10A	1.04 (3)
N3—HN3	0.77 (2)	C10—H10B	1.02 (2)
C1—C6	1.389 (2)	C10—H10C	0.98 (3)
C1—C2	1.410 (2)	C11—H11A	0.96 (2)
C1—C7	1.464 (2)	C11—H11B	1.00 (2)
C2—C3	1.382 (2)	C11—H11C	1.06 (3)
C3—O1—C11	117.43 (14)	C5—C6—H6	119.1 (12)
C4—O2—HO2	112.0 (18)	N1—C7—C1	120.67 (15)
C7—N1—N2	115.75 (14)	N1—C7—C1	120.67 (15)
C8—N2—N1	120.31 (14)	N1—C7—H7	122.7 (11)
C8—N2—N1	120.31 (14)	N1—C7—H7	122.7 (11)
C8—N2—HN2	117.5 (13)	C1—C7—H7	116.6 (11)
N1—N2—HN2	122.1 (13)	N3—C8—N2	116.42 (15)
N1—N2—HN2	122.1 (13)	N3—C8—S1	126.51 (13)
C8—N3—C9	125.82 (15)	N2—C8—S1	117.07 (12)
C8—N3—HN3	115.3 (16)	N3—C9—C10	111.04 (15)
C9—N3—HN3	118.8 (16)	N3—C9—H9A	106.1 (10)
C6—C1—C2	119.64 (15)	C10—C9—H9A	109.0 (11)
C6—C1—C7	119.69 (15)	N3—C9—H9B	111.2 (11)
C2—C1—C7	120.63 (15)	C10—C9—H9B	110.1 (11)
C3—C2—C1	119.74 (15)	H9A—C9—H9B	109.3 (16)
C3—C2—H2	120.7 (12)	C9—C10—H10A	111.8 (14)
C1—C2—H2	119.5 (12)	C9—C10—H10B	109.3 (12)
O1—C3—C2	125.22 (15)	H10A—C10—H10B	108.0 (18)
O1—C3—C4	114.69 (14)	C9—C10—H10C	111.4 (15)
C2—C3—C4	120.09 (14)	H10A—C10—H10C	109 (2)
O2—C4—C5	124.25 (15)	H10B—C10—H10C	107.4 (17)
O2—C4—C3	115.59 (14)	O1—C11—H11A	105.6 (12)
C5—C4—C3	120.17 (15)	O1—C11—H11B	110.1 (13)
C4—C5—C6	119.85 (16)	H11A—C11—H11B	113.4 (17)
C4—C5—H5	115.7 (11)	O1—C11—H11C	108.9 (13)
C6—C5—H5	124.4 (11)	H11A—C11—H11C	111.5 (19)
C1—C6—C5	120.50 (15)	H11B—C11—H11C	107 (2)
C1—C6—H6	120.4 (12)
C7—N1—N2—C8	−177.34 (16)	C7—C1—C6—C5	178.46 (16)
C6—C1—C2—C3	0.1 (3)	C4—C5—C6—C1	0.0 (3)
C7—C1—C2—C3	−177.84 (15)	N2—N1—C7—C1	−179.36 (15)
C11—O1—C3—C2	−10.6 (3)	C6—C1—C7—N1	−168.55 (16)
C11—O1—C3—C4	168.32 (16)	C2—C1—C7—N1	9.4 (3)
C1—C2—C3—O1	177.64 (16)	C6—C1—C7—N1	−168.55 (16)
C1—C2—C3—C4	−1.2 (3)	C2—C1—C7—N1	9.4 (3)
O1—C3—C4—O2	2.2 (2)	C9—N3—C8—N2	171.47 (17)
C2—C3—C4—O2	−178.86 (14)	C9—N3—C8—S1	−7.6 (3)
O1—C3—C4—C5	−177.30 (15)	N1—N2—C8—N3	−4.0 (2)
C2—C3—C4—C5	1.6 (3)	N1—N2—C8—N3	−4.0 (2)
O2—C4—C5—C6	179.51 (15)	N1—N2—C8—S1	175.21 (13)
C3—C4—C5—C6	−1.0 (3)	N1—N2—C8—S1	175.21 (13)
C2—C1—C6—C5	0.5 (2)	C8—N3—C9—C10	−99.4 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O2—HO2···S1^i	0.86 (3)	2.26 (3)	3.1144 (14)	173 (2)
N3—HN3···N1	0.77 (2)	2.25 (2)	2.643 (2)	112.4 (19)
N3—HN3···O2^ii	0.77 (2)	2.43 (2)	3.023 (2)	135 (2)
N3—HN3···O1^ii	0.77 (2)	2.52 (2)	3.061 (2)	128.3 (19)

Symmetry codes: (i) x+1, y, z−1; (ii) −x+1, −y, z+1/2.