1-[2-(2,4-Dichloro­phen­oxy)acet­yl]-4-cyclo­hexyl­thio­semicarbazide

Qadeer, G.; Rama, N.H.; Malik, M.A.; Akhtar, J.; Raftery, J.

doi:10.1107/S1600536807034022

1-[2-(2,4-Dichlorophenoxy)acetyl]-4-cyclohexylthiosemicarbazide

G. Qadeer, N. H. Rama, M. A. Malik, J. Akhtar and J. Raftery

The title compound, C₁₅H₁₉Cl₂N₃O₂S, is an important intermediate for the synthesis of biologically active heterocyclic compounds. The thiosemicarbazide group is approximately planar and forms a dihedral angle of 88.03 (5)° with the benzene ring. The structure is stabilized by intermolecular N—H

O and N—H

S hydrogen-bond interactions.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807034022/xu2290sup1.cif Contains datablocks I, global
	Structure factor file (CIF format) https://doi.org/10.1107/S1600536807034022/xu2290Isup2.hkl Contains datablock I

CCDC reference: 657769

checkCIF report

Key indicators

Single-crystal X-ray study
T = 100 K
Mean (C-C) = 0.004 Å
R factor = 0.040
wR factor = 0.107
Data-to-parameter ratio = 19.0

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT180_ALERT_3_C Check Cell Rounding: # of Values Ending with 0 =          3
PLAT431_ALERT_2_C Short Inter HL..A Contact  Cl1    ..  O2      ..       3.06 Ang.

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   2 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   0 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
   1 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

Comment top

Thiosemicarbazide is interesting because of the formation of complexes with biological activities (Shen et al., 1998). Some substituted thiourea derivatives have shown interesting biological effects, including anti-HIV properties (Mao et al., 1999), and thiourea derivatives have also been successfully screened for various biological actions (Antholine & Taketa, 1982). As a ligand with potential S– and N-atom donors, thiosemicarbazide is interesting because of the structural chemistry of its multifunctional coordination modes (N-monodentate, S-monodentate or N:S-bidentate). In order to investigate further this kind of ligand, we synthesized the title compound and describe its structure here.

In the molecule of the title compound (Fig. 1), the bond lengths and angles are in normal ranges (Ji et al., 2002). The thiosemicabazide group is approximately planar and forms a dihedral angles of 88.03 (5)° with the benzene ring. The crystal structure is stabilized by intermolecular N—-H···O and N—H··· S hydrogen bonding (Table 1). Dipole–dipole and van der Waals interactions are also effective in the molecular packing in the crystal structure.

Related literature top

For general background, see: Antholine & Taketa (1982); Mao et al. (1999); Shen et al. (1998). For the related structure, see Ji et al. (2002).

Experimental top

The title compound was prepared by the reaction of 2-(2,4-dichlorophenoxy) acetohydrazide (4.7 g, 20 mmol) and cyclohexylisothiocyanate (2.82 g, 20 mmol) in an ethanol solution (Fig. 3). Single crystals suitable for X-ray measurements were obtained by recrystallization from a water-ethanol solution at room temperature (yield: 80%).

Structure description top

For general background, see: Antholine & Taketa (1982); Mao et al. (1999); Shen et al. (1998). For the related structure, see Ji et al. (2002).

Computing details top

Data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1999); data reduction: SAINT; program(s) used to solve structure: SIR2004 (Burla et al., 2005); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1999); software used to prepare material for publication: SHELXTL.

Figures top

	Fig. 1. The molecular structure of (I) with 50% probability displacement ellipsoids (arbitrary spheres for H atoms).
	Fig. 2. Crystal packing of (I), along b axis.
	Fig. 3. The reaction scheme.

1-[2-(2,4-Dichlorophenoxy)acetyl]-4-cyclohexylthiosemicarbazide top

Crystal data top

C₁₅H₁₉Cl₂N₃O₂S	F(000) = 784
M_r = 376.29	D_x = 1.476 Mg m⁻³ D_m = 1.429 Mg m⁻³ D_m measured by not measured
Monoclinic, P2₁/c	Melting point: 462(1) K
Hall symbol: -P 2ybc	Mo Kα radiation, λ = 0.71073 Å
a = 15.4180 (16) Å	Cell parameters from 2164 reflections
b = 12.1530 (13) Å	θ = 2.1–27.5°
c = 9.285 (1) Å	µ = 0.52 mm⁻¹
β = 103.299 (2)°	T = 100 K
V = 1693.1 (3) Å³	Block, colorless
Z = 4	0.25 × 0.20 × 0.15 mm

Data collection top

Bruker SMART CCD area-detector diffractometer	3957 independent reflections
Radiation source: fine-focus sealed tube	2789 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.048
φ and ω scans	θ_max = 28.3°, θ_min = 1.3°
Absorption correction: multi-scan (SADABS; Sheldrick, 2002)	h = −18→20
T_min = 0.881, T_max = 0.926	k = −15→14
10375 measured reflections	l = −12→10

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.040	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.107	H-atom parameters constrained
S = 0.96	w = 1/[σ²(F_o²) + (0.0451P)²] where P = (F_o² + 2F_c²)/3
3957 reflections	(Δ/σ)_max = 0.001
208 parameters	Δρ_max = 0.40 e Å⁻³
0 restraints	Δρ_min = −0.31 e Å⁻³

Crystal data top

C₁₅H₁₉Cl₂N₃O₂S	V = 1693.1 (3) Å³
M_r = 376.29	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 15.4180 (16) Å	µ = 0.52 mm⁻¹
b = 12.1530 (13) Å	T = 100 K
c = 9.285 (1) Å	0.25 × 0.20 × 0.15 mm
β = 103.299 (2)°

Data collection top

Bruker SMART CCD area-detector diffractometer	3957 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 2002)	2789 reflections with I > 2σ(I)
T_min = 0.881, T_max = 0.926	R_int = 0.048
10375 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.040	0 restraints
wR(F²) = 0.107	H-atom parameters constrained
S = 0.96	Δρ_max = 0.40 e Å⁻³
3957 reflections	Δρ_min = −0.31 e Å⁻³
208 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

	x	y	z	U_iso*/U_eq
C1	0.13846 (17)	0.6689 (2)	0.7485 (3)	0.0166 (6)
C2	0.07493 (17)	0.7128 (2)	0.6323 (3)	0.0181 (6)
H2	0.0368	0.6653	0.5648	0.022*
C3	0.06700 (17)	0.8258 (2)	0.6143 (3)	0.0172 (6)
H3	0.0239	0.8561	0.5342	0.021*
C4	0.12233 (17)	0.8939 (2)	0.7139 (3)	0.0162 (6)
C5	0.18637 (17)	0.8522 (2)	0.8310 (3)	0.0159 (6)
H5	0.2237	0.9000	0.8992	0.019*
C6	0.19441 (17)	0.7396 (2)	0.8458 (3)	0.0154 (6)
C7	0.09777 (17)	0.4823 (2)	0.6805 (3)	0.0159 (6)
H7A	0.1085	0.4896	0.5799	0.019*
H7B	0.0339	0.4967	0.6750	0.019*
C8	0.12191 (16)	0.3672 (2)	0.7391 (3)	0.0143 (6)
C9	0.26704 (17)	0.1994 (2)	0.9505 (3)	0.0142 (6)
C10	0.39401 (16)	0.1555 (2)	0.8427 (3)	0.0153 (6)
H10	0.4187	0.1192	0.9401	0.018*
C11	0.36496 (17)	0.0664 (2)	0.7282 (3)	0.0187 (6)
H11A	0.3397	0.1004	0.6307	0.022*
H11B	0.3180	0.0210	0.7556	0.022*
C12	0.44379 (17)	−0.0063 (2)	0.7176 (3)	0.0209 (6)
H12A	0.4660	−0.0447	0.8130	0.025*
H12B	0.4241	−0.0626	0.6400	0.025*
C13	0.51860 (17)	0.0618 (2)	0.6807 (3)	0.0200 (6)
H13A	0.4984	0.0935	0.5804	0.024*
H13B	0.5704	0.0137	0.6808	0.024*
C14	0.54661 (18)	0.1542 (2)	0.7923 (3)	0.0219 (6)
H14A	0.5922	0.2002	0.7617	0.026*
H14B	0.5737	0.1223	0.8904	0.026*
C15	0.46748 (17)	0.2262 (2)	0.8046 (3)	0.0209 (6)
H15A	0.4870	0.2824	0.8825	0.025*
H15B	0.4442	0.2647	0.7096	0.025*
Cl1	0.11146 (4)	1.03696 (5)	0.69465 (8)	0.01992 (17)
Cl2	0.27468 (5)	0.68394 (6)	0.98848 (8)	0.02279 (18)
N1	0.17825 (14)	0.36264 (18)	0.8738 (2)	0.0151 (5)
H1	0.2046	0.4233	0.9134	0.018*
N2	0.19546 (14)	0.26475 (17)	0.9509 (3)	0.0161 (5)
H2A	0.1578	0.2434	1.0035	0.019*
N3	0.31812 (14)	0.22479 (18)	0.8581 (2)	0.0153 (5)
H3A	0.3063	0.2849	0.8043	0.018*
O1	0.15121 (12)	0.55908 (14)	0.7776 (2)	0.0207 (5)
O2	0.08986 (11)	0.28700 (14)	0.6667 (2)	0.0160 (4)
S1	0.28518 (4)	0.09197 (5)	1.06962 (8)	0.01578 (17)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0196 (14)	0.0135 (14)	0.0166 (15)	0.0021 (11)	0.0043 (12)	0.0014 (11)
C2	0.0175 (13)	0.0156 (14)	0.0192 (16)	−0.0001 (11)	0.0005 (12)	−0.0002 (12)
C3	0.0166 (13)	0.0164 (14)	0.0179 (15)	0.0020 (11)	0.0027 (11)	0.0035 (12)
C4	0.0204 (14)	0.0100 (13)	0.0201 (15)	0.0015 (11)	0.0085 (12)	0.0006 (11)
C5	0.0178 (13)	0.0150 (14)	0.0157 (14)	−0.0020 (11)	0.0054 (11)	−0.0013 (11)
C6	0.0162 (13)	0.0175 (14)	0.0121 (14)	0.0023 (11)	0.0024 (11)	0.0027 (11)
C7	0.0192 (14)	0.0112 (13)	0.0167 (15)	0.0001 (10)	0.0030 (11)	−0.0006 (11)
C8	0.0122 (13)	0.0159 (14)	0.0166 (15)	0.0018 (10)	0.0071 (11)	0.0011 (12)
C9	0.0172 (13)	0.0128 (13)	0.0122 (14)	−0.0016 (10)	0.0025 (11)	−0.0023 (11)
C10	0.0146 (13)	0.0151 (14)	0.0173 (15)	0.0035 (10)	0.0056 (11)	0.0025 (11)
C11	0.0167 (14)	0.0186 (15)	0.0218 (16)	0.0005 (11)	0.0065 (12)	−0.0014 (12)
C12	0.0200 (14)	0.0165 (14)	0.0266 (17)	0.0017 (11)	0.0063 (13)	−0.0040 (12)
C13	0.0177 (14)	0.0222 (16)	0.0214 (16)	0.0036 (11)	0.0071 (12)	−0.0035 (12)
C14	0.0156 (14)	0.0252 (16)	0.0260 (17)	−0.0038 (11)	0.0070 (12)	−0.0037 (13)
C15	0.0215 (14)	0.0170 (15)	0.0270 (17)	−0.0033 (11)	0.0112 (13)	−0.0039 (13)
Cl1	0.0222 (4)	0.0109 (3)	0.0265 (4)	0.0006 (3)	0.0052 (3)	0.0030 (3)
Cl2	0.0248 (4)	0.0185 (4)	0.0204 (4)	0.0000 (3)	−0.0043 (3)	0.0030 (3)
N1	0.0213 (12)	0.0097 (11)	0.0154 (12)	0.0000 (9)	0.0061 (10)	0.0012 (9)
N2	0.0204 (12)	0.0133 (12)	0.0173 (13)	0.0039 (9)	0.0094 (10)	0.0050 (10)
N3	0.0193 (12)	0.0125 (11)	0.0162 (13)	0.0026 (9)	0.0081 (10)	0.0038 (9)
O1	0.0265 (11)	0.0093 (10)	0.0212 (11)	0.0006 (8)	−0.0052 (9)	0.0000 (8)
O2	0.0196 (9)	0.0125 (10)	0.0171 (10)	−0.0026 (7)	0.0069 (8)	−0.0024 (8)
S1	0.0204 (3)	0.0133 (3)	0.0143 (4)	0.0018 (3)	0.0053 (3)	0.0020 (3)

Geometric parameters (Å, º) top

C1—O1	1.367 (3)	C10—C11	1.511 (4)
C1—C2	1.387 (4)	C10—C15	1.527 (4)
C1—C6	1.393 (4)	C10—H10	1.0000
C2—C3	1.386 (4)	C11—C12	1.524 (4)
C2—H2	0.9500	C11—H11A	0.9900
C3—C4	1.381 (4)	C11—H11B	0.9900
C3—H3	0.9500	C12—C13	1.521 (4)
C4—C5	1.385 (4)	C12—H12A	0.9900
C4—Cl1	1.752 (3)	C12—H12B	0.9900
C5—C6	1.378 (4)	C13—C14	1.521 (4)
C5—H5	0.9500	C13—H13A	0.9900
C6—Cl2	1.729 (3)	C13—H13B	0.9900
C7—O1	1.421 (3)	C14—C15	1.527 (4)
C7—C8	1.516 (4)	C14—H14A	0.9900
C7—H7A	0.9900	C14—H14B	0.9900
C7—H7B	0.9900	C15—H15A	0.9900
C8—O2	1.222 (3)	C15—H15B	0.9900
C8—N1	1.350 (3)	N1—N2	1.382 (3)
C9—N3	1.327 (3)	N1—H1	0.8800
C9—N2	1.360 (3)	N2—H2A	0.8800
C9—S1	1.693 (3)	N3—H3A	0.8800
C10—N3	1.475 (3)

O1—C1—C2	125.0 (2)	C12—C11—H11A	109.6
O1—C1—C6	115.8 (2)	C10—C11—H11B	109.6
C2—C1—C6	119.2 (2)	C12—C11—H11B	109.6
C3—C2—C1	120.1 (3)	H11A—C11—H11B	108.1
C3—C2—H2	119.9	C13—C12—C11	110.9 (2)
C1—C2—H2	119.9	C13—C12—H12A	109.5
C4—C3—C2	119.3 (3)	C11—C12—H12A	109.5
C4—C3—H3	120.3	C13—C12—H12B	109.5
C2—C3—H3	120.3	C11—C12—H12B	109.5
C3—C4—C5	121.7 (2)	H12A—C12—H12B	108.1
C3—C4—Cl1	119.8 (2)	C12—C13—C14	111.1 (2)
C5—C4—Cl1	118.5 (2)	C12—C13—H13A	109.4
C6—C5—C4	118.2 (3)	C14—C13—H13A	109.4
C6—C5—H5	120.9	C12—C13—H13B	109.4
C4—C5—H5	120.9	C14—C13—H13B	109.4
C5—C6—C1	121.3 (2)	H13A—C13—H13B	108.0
C5—C6—Cl2	119.8 (2)	C13—C14—C15	111.6 (2)
C1—C6—Cl2	118.9 (2)	C13—C14—H14A	109.3
O1—C7—C8	108.7 (2)	C15—C14—H14A	109.3
O1—C7—H7A	110.0	C13—C14—H14B	109.3
C8—C7—H7A	110.0	C15—C14—H14B	109.3
O1—C7—H7B	110.0	H14A—C14—H14B	108.0
C8—C7—H7B	110.0	C10—C15—C14	110.1 (2)
H7A—C7—H7B	108.3	C10—C15—H15A	109.6
O2—C8—N1	124.7 (2)	C14—C15—H15A	109.6
O2—C8—C7	120.2 (2)	C10—C15—H15B	109.6
N1—C8—C7	115.0 (2)	C14—C15—H15B	109.6
N3—C9—N2	118.0 (2)	H15A—C15—H15B	108.2
N3—C9—S1	124.60 (19)	C8—N1—N2	121.4 (2)
N2—C9—S1	117.4 (2)	C8—N1—H1	119.3
N3—C10—C11	111.3 (2)	N2—N1—H1	119.3
N3—C10—C15	110.4 (2)	C9—N2—N1	124.1 (2)
C11—C10—C15	110.9 (2)	C9—N2—H2A	118.0
N3—C10—H10	108.0	N1—N2—H2A	118.0
C11—C10—H10	108.0	C9—N3—C10	122.2 (2)
C15—C10—H10	108.0	C9—N3—H3A	118.9
C10—C11—C12	110.4 (2)	C10—N3—H3A	118.9
C10—C11—H11A	109.6	C1—O1—C7	118.7 (2)

O1—C1—C2—C3	179.1 (2)	C11—C12—C13—C14	55.5 (3)
C6—C1—C2—C3	−0.5 (4)	C12—C13—C14—C15	−55.0 (3)
C1—C2—C3—C4	−0.6 (4)	N3—C10—C15—C14	178.7 (2)
C2—C3—C4—C5	0.6 (4)	C11—C10—C15—C14	−57.4 (3)
C2—C3—C4—Cl1	−178.7 (2)	C13—C14—C15—C10	55.6 (3)
C3—C4—C5—C6	0.5 (4)	O2—C8—N1—N2	−8.8 (4)
Cl1—C4—C5—C6	179.8 (2)	C7—C8—N1—N2	170.0 (2)
C4—C5—C6—C1	−1.6 (4)	N3—C9—N2—N1	−7.7 (4)
C4—C5—C6—Cl2	178.93 (19)	S1—C9—N2—N1	171.72 (19)
O1—C1—C6—C5	−178.0 (2)	C8—N1—N2—C9	96.4 (3)
C2—C1—C6—C5	1.7 (4)	N2—C9—N3—C10	−176.2 (2)
O1—C1—C6—Cl2	1.4 (3)	S1—C9—N3—C10	4.4 (4)
C2—C1—C6—Cl2	−178.9 (2)	C11—C10—N3—C9	87.9 (3)
O1—C7—C8—O2	−173.6 (2)	C15—C10—N3—C9	−148.5 (2)
O1—C7—C8—N1	7.5 (3)	C2—C1—O1—C7	1.8 (4)
N3—C10—C11—C12	−178.2 (2)	C6—C1—O1—C7	−178.5 (2)
C15—C10—C11—C12	58.5 (3)	C8—C7—O1—C1	−177.9 (2)
C10—C11—C12—C13	−57.3 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···O2ⁱ	0.88	2.06	2.926 (3)	166
N3—H3A···S1ⁱⁱ	0.88	2.60	3.430 (2)	157

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

Experimental details

Crystal data
Chemical formula	C₁₅H₁₉Cl₂N₃O₂S
M_r	376.29
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	100
a, b, c (Å)	15.4180 (16), 12.1530 (13), 9.285 (1)
β (°)	103.299 (2)
V (Å³)	1693.1 (3)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.52
Crystal size (mm)	0.25 × 0.20 × 0.15

Data collection
Diffractometer	Bruker SMART CCD area-detector
Absorption correction	Multi-scan (SADABS; Sheldrick, 2002)
T_min, T_max	0.881, 0.926
No. of measured, independent and observed [I > 2σ(I)] reflections	10375, 3957, 2789
R_int	0.048
(sin θ/λ)_max (Å⁻¹)	0.667

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.040, 0.107, 0.96
No. of reflections	3957
No. of parameters	208
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.40, −0.31

Computer programs: SMART (Bruker, 1998), SAINT (Bruker, 1999), SAINT, SIR2004 (Burla et al., 2005), SHELXL97 (Sheldrick, 1997), SHELXTL (Bruker, 1999), SHELXTL.