(E)-1-[(2-Chloro-5-methyl­pyridin-3-yl)methyl­ene]thiosemicarbazide

Wang, Z.; Ma, Y.; Xu, Y.; Ling, Y.; Yang, X.

doi:10.1107/S1600536810004915

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 66| Part 3| March 2010| Page o604

doi:10.1107/S1600536810004915

Open

access

(E)-1-[(2-Chloro-5-methylpyridin-3-yl)methylene]thiosemicarbazide

Zhen Wang,^a Yongqiang Ma,^a Yan Xu,^a Yun Ling ^a and Xinling Yang ^a ^*

^aCollege of Science, China Agricultural University, Beijing, 100193, People's Republic of China.
^*Correspondence e-mail: yangxl@cau.edu.cn

(Received 15 January 2010; accepted 8 February 2010; online 13 February 2010)

The title compound, C₈H₉ClN₄S, which has potential insecticidal activity, was synthesized by the reaction of 2-chloro-5-methylnicotinaldehyde and thiosemicarbazide. In the crystal structure, the molecules are linked via intermolecular N—H⋯N, N—H⋯S and N—H⋯Cl hydrogen bonds, forming a three-dimensional network stacked down a.

Related literature

Tyrosinase is a key enzyme in the moulting process of insects, see: Kramer & Knost (2001 ). For the inhibitory activity on tyrosinase of benzaldehyde thiosemicarbazones, see: Xue et al. (2007 ). For the synthesis of the title compound, see: Liu et al. (2008 ).

Experimental

Crystal data

C₈H₉ClN₄S
M_r = 228.70
Monoclinic, P 2₁ /c
a = 8.776 (3) Å
b = 15.523 (4) Å
c = 7.540 (2) Å
β = 96.193 (16)°
V = 1021.2 (5) Å³
Z = 4
Cu Kα radiation
μ = 4.95 mm⁻¹
T = 173 K
0.45 × 0.30 × 0.30 mm

Data collection

Rigaku R-AXIS Rapid diffractometer
Absorption correction: numerical (ABSCOR; Higashi, 1995 ) T_min = 0.214, T_max = 0.319
6565 measured reflections
1847 independent reflections
1598 reflections with I > 2σ(I)
R_int = 0.048

Refinement

R[F² > 2σ(F²)] = 0.037
wR(F²) = 0.105
S = 1.11
1847 reflections
129 parameters
H-atom parameters constrained
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3B⋯S1ⁱ	0.88	2.52	3.379 (2)	166
N4—H4B⋯N1ⁱⁱ	0.88	2.15	3.012 (3)	168
N4—H4B⋯Cl1ⁱⁱ	0.88	2.98	3.609 (2)	130
Symmetry codes: (i) -x+2, -y+1, -z; (ii) $[x+1, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]$ .

Data collection: RAPID-AUTO (Rigaku, 2001 ); cell refinement: RAPID-AUTO; data reduction: RAPID-AUTO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks I, New_Global_Publ_Block. DOI: 10.1107/S1600536810004915/ds2018sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536810004915/ds2018Isup2.hkl

checkCIF report

Comment top

Tyrosinase is a key enzyme in the molting process of insect (Kramer & Knost 2001), and benzaldehyde thiosemicarbazones have inhibitory activity on tyrosinase (Xue et al., 2007). In order to look for highly potent tyrosinase inhibitors, the title compound was synthesized by the reaction of thiosemicarbazide and 2-chloro-5-methylnicotinaldehyde (Liu et al., 2008). Finally in the preliminary bioassay, we found that it showed obvious inhibitory activity against tyrosinase from cotton bollworm. To get more information about the structure, we prepared a single crystal of the title compound and its crystal will be reported herein.

The bond distances between N2 and C7 is 1.277 (3) Å, which is in the range of typical bond length of imine double bond. The bond distance of 1.683 (2) Å for the thiocarbonyl group (S1–C8) is about the average value of the typical C=S double bond (1.56 Å) and C–S single bond (1.82 Å), showing a partial double bond character in feature. The partial double bond character also appears between N3 and C8 as well as N4 and C8, which show the distance of 1.355 (3) and 1.322 (3) Å, respectively. In the cryatal structure, there are three intermolecular hydrogen bonds: N3–H3···S1, N4–H4···N1, N4–H4···Cl1 (Table 1).

Related literature top

Tyrosinase is a key enzyme in the moulting process of insects, see: Kramer & Knost (2001). Benzaldehyde thiosemicarbazones have inhibitory activity on tyrosinase, see: Xue et al. (2007). For the synthesis of the title compound, see: Liu et al. (2008).

Experimental top

1.6 g (10 mmol) 2-Chloro-5-methylnicotinaldehyde was dissolved in anhydrous ethanol (15 ml). To this solution, 0.91 g (10 mmol) thiosemicarbazide and 0.5 mL acetic acid were added. The mixture was refluxed for 24 h and then cooled to room temperatur. The precipitate was formed and collected after filteration. The title compound was obtained in 89% yield after recrystallization of the precipitate from anhydrous MeOH. The colourless crystals suitable for X-ray crystallography was carefully grown from anhydrous methanolic solution.

Computing details top

Data collection: RAPID-AUTO (Rigaku, 2001); cell refinement: RAPID-AUTO (Rigaku, 2001); data reduction: RAPID-AUTO (Rigaku, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELX97 (Sheldrick, 2008).

Figures top

	Fig. 1. The molecular structure of the title compound , showing the labelling scheme. Displacement ellipsoids are drawn at the 30% probability level for all non-H atoms.
	Fig. 2. Packing diagram for the title compound viewed along the a axis.

(E)-1-[(2-Chloro-5-methylpyridin-3-yl)methylene]thiosemicarbazide top

Crystal data top

C₈H₉ClN₄S	F(000) = 472
M_r = 228.70	D_x = 1.488 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54186 Å
Hall symbol: -P 2ybc	Cell parameters from 658 reflections
a = 8.776 (3) Å	θ = 3.1–66.2°
b = 15.523 (4) Å	µ = 4.95 mm⁻¹
c = 7.540 (2) Å	T = 173 K
β = 96.193 (16)°	Block, colorless
V = 1021.2 (5) Å³	0.45 × 0.30 × 0.30 mm
Z = 4

Data collection top

Rigaku R-AXIS Rapid diffractometer	1847 independent reflections
Radiation source: rotating anode	1598 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.048
ω scans at fixed χ = 45°	θ_max = 68.3°, θ_min = 5.1°
Absorption correction: numerical (ABSCOR; Higashi, 1995)	h = −10→9
T_min = 0.214, T_max = 0.319	k = −18→17
6565 measured reflections	l = −8→9

Refinement top

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)] = 0.037	H-atom parameters constrained
wR(F²) = 0.105	w = 1/[σ²(F_o²) + (0.0431P)² + 0.4188P] where P = (F_o² + 2F_c²)/3
S = 1.11	(Δ/σ)_max = 0.001
1847 reflections	Δρ_max = 0.27 e Å⁻³
129 parameters	Δρ_min = −0.22 e Å⁻³
0 restraints	Extinction correction: SHELXL, Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0051 (7)

Crystal data top

C₈H₉ClN₄S	V = 1021.2 (5) Å³
M_r = 228.70	Z = 4
Monoclinic, P2₁/c	Cu Kα radiation
a = 8.776 (3) Å	µ = 4.95 mm⁻¹
b = 15.523 (4) Å	T = 173 K
c = 7.540 (2) Å	0.45 × 0.30 × 0.30 mm
β = 96.193 (16)°

Data collection top

Rigaku R-AXIS Rapid diffractometer	1847 independent reflections
Absorption correction: numerical (ABSCOR; Higashi, 1995)	1598 reflections with I > 2σ(I)
T_min = 0.214, T_max = 0.319	R_int = 0.048
6565 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.037	0 restraints
wR(F²) = 0.105	H-atom parameters constrained
S = 1.11	Δρ_max = 0.27 e Å⁻³
1847 reflections	Δρ_min = −0.22 e Å⁻³
129 parameters

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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

	x	y	z	U_iso*/U_eq
Cl1	0.50443 (6)	0.31852 (4)	0.16529 (8)	0.0385 (2)
S1	1.21803 (7)	0.48033 (4)	−0.12061 (9)	0.0413 (2)
N1	0.5116 (2)	0.15225 (14)	0.1900 (3)	0.0341 (5)
N2	0.9510 (2)	0.28984 (13)	−0.0128 (2)	0.0309 (5)
N3	1.0139 (2)	0.36918 (13)	−0.0313 (3)	0.0349 (5)
H3B	0.9687	0.4145	0.0097	0.042*
N4	1.2069 (2)	0.31191 (13)	−0.1757 (3)	0.0380 (5)
H4A	1.1645	0.2609	−0.1669	0.046*
H4B	1.2914	0.3171	−0.2281	0.046*
C1	0.5935 (3)	0.21864 (16)	0.1461 (3)	0.0308 (5)
C2	0.7391 (2)	0.21399 (15)	0.0899 (3)	0.0289 (5)
C3	0.7996 (3)	0.13151 (16)	0.0783 (3)	0.0315 (5)
H3A	0.8979	0.1246	0.0385	0.038*
C4	0.7192 (3)	0.05922 (17)	0.1237 (3)	0.0336 (5)
C5	0.5753 (3)	0.07344 (16)	0.1798 (3)	0.0357 (6)
H5A	0.5186	0.0249	0.2129	0.043*
C6	0.7836 (3)	−0.03035 (16)	0.1176 (3)	0.0407 (6)
H6A	0.8908	−0.0302	0.1699	0.061*
H6B	0.7779	−0.0498	−0.0067	0.061*
H6C	0.7241	−0.0694	0.1854	0.061*
C7	0.8228 (3)	0.29122 (16)	0.0529 (3)	0.0340 (5)
H7A	0.7804	0.3455	0.0787	0.041*
C8	1.1438 (3)	0.38067 (15)	−0.1105 (3)	0.0305 (5)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0293 (3)	0.0389 (4)	0.0493 (4)	0.0043 (2)	0.0141 (3)	0.0027 (2)
S1	0.0337 (4)	0.0357 (4)	0.0589 (4)	−0.0051 (3)	0.0259 (3)	−0.0051 (3)
N1	0.0275 (10)	0.0380 (11)	0.0387 (11)	0.0010 (9)	0.0119 (8)	0.0023 (9)
N2	0.0255 (10)	0.0368 (11)	0.0313 (10)	−0.0025 (8)	0.0063 (8)	0.0003 (8)
N3	0.0256 (10)	0.0369 (12)	0.0449 (12)	−0.0032 (8)	0.0155 (9)	−0.0046 (9)
N4	0.0283 (11)	0.0369 (12)	0.0519 (13)	−0.0026 (8)	0.0184 (9)	−0.0073 (9)
C1	0.0266 (12)	0.0381 (14)	0.0284 (11)	0.0031 (10)	0.0057 (9)	−0.0013 (9)
C2	0.0242 (11)	0.0374 (14)	0.0263 (11)	−0.0030 (9)	0.0075 (9)	−0.0010 (9)
C3	0.0230 (11)	0.0434 (14)	0.0293 (12)	0.0010 (10)	0.0080 (9)	−0.0014 (10)
C4	0.0290 (12)	0.0422 (14)	0.0307 (12)	0.0001 (10)	0.0080 (9)	−0.0007 (10)
C5	0.0311 (13)	0.0357 (14)	0.0422 (13)	−0.0027 (10)	0.0122 (10)	0.0020 (10)
C6	0.0385 (14)	0.0381 (15)	0.0474 (15)	0.0015 (11)	0.0138 (12)	0.0007 (11)
C7	0.0283 (12)	0.0341 (13)	0.0413 (14)	−0.0017 (10)	0.0115 (10)	−0.0002 (10)
C8	0.0230 (11)	0.0371 (14)	0.0325 (12)	−0.0019 (9)	0.0078 (9)	−0.0004 (9)

Geometric parameters (Å, º) top

Cl1—C1	1.749 (2)	C2—C3	1.392 (3)
S1—C8	1.683 (2)	C2—C7	1.449 (3)
N1—C1	1.319 (3)	C3—C4	1.388 (3)
N1—C5	1.350 (3)	C3—H3A	0.9500
N2—C7	1.277 (3)	C4—C5	1.393 (3)
N2—N3	1.363 (3)	C4—C6	1.503 (3)
N3—C8	1.355 (3)	C5—H5A	0.9500
N3—H3B	0.8800	C6—H6A	0.9800
N4—C8	1.322 (3)	C6—H6B	0.9800
N4—H4A	0.8800	C6—H6C	0.9800
N4—H4B	0.8800	C7—H7A	0.9500
C1—C2	1.391 (3)

C1—N1—C5	117.0 (2)	C3—C4—C6	122.5 (2)
C7—N2—N3	114.1 (2)	C5—C4—C6	120.8 (2)
C8—N3—N2	122.2 (2)	N1—C5—C4	123.7 (2)
C8—N3—H3B	118.9	N1—C5—H5A	118.1
N2—N3—H3B	118.9	C4—C5—H5A	118.1
C8—N4—H4A	120.0	C4—C6—H6A	109.5
C8—N4—H4B	120.0	C4—C6—H6B	109.5
H4A—N4—H4B	120.0	H6A—C6—H6B	109.5
N1—C1—C2	125.4 (2)	C4—C6—H6C	109.5
N1—C1—Cl1	114.30 (17)	H6A—C6—H6C	109.5
C2—C1—Cl1	120.30 (19)	H6B—C6—H6C	109.5
C1—C2—C3	115.8 (2)	N2—C7—C2	123.2 (2)
C1—C2—C7	121.2 (2)	N2—C7—H7A	118.4
C3—C2—C7	123.0 (2)	C2—C7—H7A	118.4
C4—C3—C2	121.4 (2)	N4—C8—N3	117.7 (2)
C4—C3—H3A	119.3	N4—C8—S1	123.06 (18)
C2—C3—H3A	119.3	N3—C8—S1	119.29 (18)
C3—C4—C5	116.7 (2)

C7—N2—N3—C8	−175.1 (2)	C2—C3—C4—C6	−178.2 (2)
C5—N1—C1—C2	0.2 (3)	C1—N1—C5—C4	−1.0 (3)
C5—N1—C1—Cl1	−179.23 (17)	C3—C4—C5—N1	0.7 (4)
N1—C1—C2—C3	0.8 (3)	C6—C4—C5—N1	179.4 (2)
Cl1—C1—C2—C3	−179.73 (16)	N3—N2—C7—C2	−177.63 (19)
N1—C1—C2—C7	−177.0 (2)	C1—C2—C7—N2	−174.1 (2)
Cl1—C1—C2—C7	2.5 (3)	C3—C2—C7—N2	8.3 (4)
C1—C2—C3—C4	−1.2 (3)	N2—N3—C8—N4	2.0 (3)
C7—C2—C3—C4	176.6 (2)	N2—N3—C8—S1	−177.57 (16)
C2—C3—C4—C5	0.5 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3B···S1ⁱ	0.88	2.52	3.379 (2)	166
N4—H4B···N1ⁱⁱ	0.88	2.15	3.012 (3)	168
N4—H4B···Cl1ⁱⁱ	0.88	2.98	3.609 (2)	130

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

Experimental details

Crystal data
Chemical formula	C₈H₉ClN₄S
M_r	228.70
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	173
a, b, c (Å)	8.776 (3), 15.523 (4), 7.540 (2)
β (°)	96.193 (16)
V (Å³)	1021.2 (5)
Z	4
Radiation type	Cu Kα
µ (mm⁻¹)	4.95
Crystal size (mm)	0.45 × 0.30 × 0.30

Data collection
Diffractometer	Rigaku R-AXIS Rapid diffractometer
Absorption correction	Numerical (ABSCOR; Higashi, 1995)
T_min, T_max	0.214, 0.319
No. of measured, independent and observed [I > 2σ(I)] reflections	6565, 1847, 1598
R_int	0.048
(sin θ/λ)_max (Å⁻¹)	0.602

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.037, 0.105, 1.11
No. of reflections	1847
No. of parameters	129
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.27, −0.22

Computer programs: RAPID-AUTO (Rigaku, 2001), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), XP in SHELXTL (Sheldrick, 2008), SHELX97 (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3B···S1ⁱ	0.88	2.52	3.379 (2)	165.7
N4—H4B···N1ⁱⁱ	0.88	2.15	3.012 (3)	167.9
N4—H4B···Cl1ⁱⁱ	0.88	2.98	3.609 (2)	129.7

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

Acknowledgements

This work was supported by the National High Technology Research and Development Program of China (2006 A A10A201). We acknowledge Dr Liang Tongling for collecting the data at the Analysis and Testing Center, Institute of Chemistry Academy of Science, Beijing.

References

Higashi, T. (1995). ABSCOR. Rigaku Corporation, Tokyo, Japan. Google Scholar
Kramer, K. J. & Knost, M. R. (2001). Tetrahedron, 57, 385-392. Web of Science CrossRef CAS Google Scholar
Liu, J., Yi, W., Wan, Y., Ma, L. & Song, H. (2008). Bioorg. Med. Chem. 16, 1096–1102. Web of Science CrossRef PubMed CAS Google Scholar
Rigaku (2001). RAPID-AUTO. Rigaku Corporation, Tokyo, Japan. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Xue, C.-B., Zhang, L., Luo, W.-C., Xie, X.-Y., Jiang, L. & Xiao, T. (2007). Bioorg. Med. Chem. 15, 2006–2015. Web of Science CrossRef PubMed CAS Google Scholar