1-[2-(4-Chloro­phen­yl)acet­yl]-4-(2-methoxy­phen­yl)thio­semicarbazide

Khan, R.A.H.; Iqbal, R.; Habib-ur-Rehman; Qadeer, G.; Su, Z.-M.

doi:10.1107/S1600536807030048

1-[2-(4-Chlorophenyl)acetyl]-4-(2-methoxyphenyl)thiosemicarbazide

R. A. H. Khan, R. Iqbal, Habib-ur-Rehman, G. Qadeer and Z.-M. Su

The title compound, C₁₆H₁₆ClN₃O₂S, is an important intermediate for the synthesis of biologically active heterocyclic compounds. In the molecule, the thiosemicarbazide group is approximately planar and forms dihedral angles of 33.03 (6) and 45.48 (5)° with the benzene rings. The structure is stabilized by intramolecular N—H

O, N—H

N and C—H

S hydrogen bonds and intermolecular N—H

O and N—H

S hydrogen bonds.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807030048/xu2274sup1.cif Contains datablocks I, global
	Structure factor file (CIF format) https://doi.org/10.1107/S1600536807030048/xu2274Isup2.hkl Contains datablock I

CCDC reference: 655022

checkCIF report

Key indicators

Single-crystal X-ray study
T = 293 K
Mean (C-C) = 0.003 Å
R factor = 0.040
wR factor = 0.111
Data-to-parameter ratio = 18.5

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT153_ALERT_1_C The su's on the Cell Axes   are Equal (x 100000)        500 Ang.
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for         C1

Alert level G
PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature        293 K
PLAT200_ALERT_1_G Check the Reported _diffrn_ambient_temperature .        293 K

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

   3 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
   0 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 (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 titel compound (Fig. 1), the bond lengths and angles are in normal ranges (Allen et al., 1987). The thiosemicarbazide is approximately planar, maximum displacement being 0.132 (2) Å for atom N2, and forms dihedral angles of 33.03 (6)° and 45.48 (5)° with the benzene rings. The dihedral angles between the benzene rings is 55.29 (3)°. The structure is stabilized by intra-molecular N—H···O, N—H···N and C—H···S hydrogen bonding and by inter-molecular N—H···O and N—H···S hydrogen bonding (Table 1).

Related literature top

For general background, see Shen et al. (1998); Mao et al. (1999); Antholine & Taketa (1982). For related literature, see: Allen et al. (1987).

Experimental top

2-(4-Chlorophenyl)acetohydrazide (3.68 g, 20 mmol) was dissolved in absolute ethanol (200 ml). 2-Methoxyphenyl isothiocyanate (3.3 g, 20 mmol) was dissolved in ethanol (100 ml). The two solution were mixed with continuous stirring. The mixture was then refluxed and the completion of reaction was monitored by TLC. After the completion of the reaction (Fig. 2), the mixture was cooled to room temperature to get the crude solid. The crude crystalline solid was then filtered. Single crystals suitable for X-ray measurements were obtained by recrystallization from an aqueous-ethanol solution at room temperature (yield: 86%).

Structure description top

For general background, see Shen et al. (1998); Mao et al. (1999); Antholine & Taketa (1982). For related literature, see: Allen et al. (1987).

Computing details top

Data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1997); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1997); software used to prepare material for publication: SHELXTL, PARST (Nardelli, 1995) and PLATON (Spek, 2003).

Figures top

	Fig. 1. The molecular structure of (I) with 50% probability displacement ellipsoids (arbitrary spheres for H atoms).
	Fig. 2. The reaction scheme.

1-[2-(4-Chlorophenyl)acetyl]-4-(2-methoxyphenyl)thiosemicarbazide top

Crystal data top

C₁₆H₁₆ClN₃O₂S	F(000) = 728
M_r = 349.83	D_x = 1.371 Mg m⁻³
Monoclinic, P2₁/n	Melting point: 432(1) K
Hall symbol: -P 2yn	Mo Kα radiation, λ = 0.71069 Å
a = 5.935 (5) Å	Cell parameters from 1520 reflections
b = 16.970 (5) Å	θ = 2.7–24.9°
c = 17.038 (5) Å	µ = 0.36 mm⁻¹
β = 98.948 (5)°	T = 293 K
V = 1695.1 (16) Å³	Block, colourless
Z = 4	0.36 × 0.31 × 0.21 mm

Data collection top

Bruker APEXII diffractometer	4083 independent reflections
Radiation source: fine-focus sealed tube	3190 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.020
φ and ω scans	θ_max = 28.3°, θ_min = 1.7°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −7→7
T_min = 0.881, T_max = 0.928	k = −9→22
10318 measured reflections	l = −22→22

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) = 0.111	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	w = 1/[σ²(F_o²) + (0.0521P)² + 0.2584P] where P = (F_o² + 2F_c²)/3
4083 reflections	(Δ/σ)_max < 0.001
221 parameters	Δρ_max = 0.24 e Å⁻³
0 restraints	Δρ_min = −0.34 e Å⁻³

Crystal data top

C₁₆H₁₆ClN₃O₂S	V = 1695.1 (16) Å³
M_r = 349.83	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 5.935 (5) Å	µ = 0.36 mm⁻¹
b = 16.970 (5) Å	T = 293 K
c = 17.038 (5) Å	0.36 × 0.31 × 0.21 mm
β = 98.948 (5)°

Data collection top

Bruker APEXII diffractometer	4083 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	3190 reflections with I > 2σ(I)
T_min = 0.881, T_max = 0.928	R_int = 0.020
10318 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.040	0 restraints
wR(F²) = 0.111	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	Δρ_max = 0.24 e Å⁻³
4083 reflections	Δρ_min = −0.34 e Å⁻³
221 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
S1	0.46464 (7)	0.03318 (2)	0.20016 (3)	0.06242 (15)
Cl1	−0.51266 (12)	0.46846 (3)	−0.10995 (4)	0.1040 (2)
O1	−0.0087 (2)	0.09248 (7)	−0.02343 (7)	0.0602 (3)
O2	0.04254 (19)	0.30128 (6)	0.13643 (7)	0.0631 (3)
N3	0.2018 (2)	0.16318 (7)	0.16729 (8)	0.0513 (3)
C10	0.3444 (2)	0.22540 (9)	0.19978 (8)	0.0466 (3)
N2	0.0441 (2)	0.04438 (8)	0.13054 (9)	0.0533 (3)
N1	−0.1492 (2)	0.08226 (8)	0.09156 (8)	0.0520 (3)
C11	0.5588 (3)	0.21836 (11)	0.24479 (9)	0.0576 (4)
H11	0.6248	0.1689	0.2546	0.069*
C15	0.2504 (2)	0.30081 (9)	0.18458 (9)	0.0494 (3)
C8	−0.1695 (3)	0.09808 (8)	0.01264 (10)	0.0497 (3)
C9	0.2302 (2)	0.08540 (8)	0.16440 (9)	0.0466 (3)
C7	−0.4040 (3)	0.12490 (10)	−0.02463 (11)	0.0596 (4)
H7A	−0.5118	0.1114	0.0106	0.072*
H7B	−0.4481	0.0965	−0.0740	0.072*
C3	−0.5936 (3)	0.25642 (11)	−0.01775 (10)	0.0590 (4)
H3	−0.6926	0.2327	0.0124	0.071*
C4	−0.4195 (2)	0.21246 (9)	−0.04146 (9)	0.0481 (3)
C6	−0.2969 (3)	0.32856 (10)	−0.10469 (10)	0.0608 (4)
H6	−0.1955	0.3531	−0.1333	0.073*
C2	−0.6225 (3)	0.33490 (11)	−0.03821 (11)	0.0670 (5)
H2	−0.7416	0.3636	−0.0227	0.080*
C16	−0.0646 (3)	0.37530 (11)	0.11639 (12)	0.0712 (5)
H16A	−0.0862	0.4024	0.1641	0.107*
H16B	−0.2099	0.3668	0.0839	0.107*
H16C	0.0301	0.4065	0.0876	0.107*
C12	0.6742 (3)	0.28520 (13)	0.27499 (11)	0.0678 (5)
H12	0.8193	0.2804	0.3044	0.081*
C5	−0.2709 (3)	0.24995 (10)	−0.08487 (10)	0.0548 (4)
H5	−0.1519	0.2215	−0.1008	0.066*
C14	0.3653 (3)	0.36647 (10)	0.21688 (10)	0.0620 (4)
H14	0.3003	0.4162	0.2082	0.074*
C1	−0.4738 (3)	0.37023 (10)	−0.08173 (10)	0.0612 (4)
C13	0.5786 (3)	0.35796 (12)	0.26236 (11)	0.0702 (5)
H13	0.6569	0.4021	0.2844	0.084*
H2N	0.058 (3)	−0.0038 (11)	0.1154 (10)	0.060 (5)*
H1N	−0.267 (3)	0.0779 (10)	0.1151 (11)	0.065 (5)*
H3N	0.077 (3)	0.1785 (10)	0.1470 (10)	0.057 (5)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0499 (2)	0.0534 (2)	0.0833 (3)	0.01080 (17)	0.0084 (2)	0.0213 (2)
Cl1	0.1198 (5)	0.0613 (3)	0.1301 (5)	0.0233 (3)	0.0165 (4)	0.0244 (3)
O1	0.0582 (7)	0.0519 (6)	0.0728 (7)	0.0018 (5)	0.0174 (6)	0.0054 (5)
O2	0.0571 (7)	0.0471 (6)	0.0800 (8)	0.0093 (5)	−0.0057 (6)	−0.0036 (5)
N3	0.0436 (7)	0.0437 (7)	0.0629 (8)	0.0046 (5)	−0.0029 (6)	0.0008 (6)
C10	0.0468 (7)	0.0492 (8)	0.0436 (7)	−0.0013 (6)	0.0067 (6)	−0.0002 (6)
N2	0.0489 (7)	0.0399 (7)	0.0698 (8)	0.0037 (5)	0.0048 (6)	0.0019 (6)
N1	0.0412 (7)	0.0505 (7)	0.0642 (8)	0.0012 (5)	0.0078 (6)	−0.0001 (6)
C11	0.0525 (9)	0.0649 (10)	0.0526 (8)	0.0017 (7)	−0.0011 (7)	0.0027 (7)
C15	0.0492 (8)	0.0502 (8)	0.0494 (8)	0.0003 (6)	0.0094 (6)	−0.0015 (6)
C8	0.0482 (8)	0.0338 (7)	0.0658 (9)	−0.0054 (6)	0.0051 (7)	−0.0012 (6)
C9	0.0454 (7)	0.0457 (8)	0.0501 (8)	0.0033 (6)	0.0115 (6)	0.0084 (6)
C7	0.0483 (8)	0.0532 (9)	0.0735 (10)	−0.0073 (7)	−0.0024 (7)	0.0029 (8)
C3	0.0510 (9)	0.0697 (11)	0.0583 (9)	0.0021 (7)	0.0147 (7)	0.0045 (8)
C4	0.0410 (7)	0.0540 (8)	0.0467 (7)	−0.0004 (6)	−0.0017 (6)	0.0005 (6)
C6	0.0588 (9)	0.0623 (10)	0.0625 (10)	0.0014 (8)	0.0137 (8)	0.0098 (8)
C2	0.0593 (10)	0.0709 (11)	0.0726 (11)	0.0182 (9)	0.0159 (8)	−0.0026 (9)
C16	0.0758 (12)	0.0563 (10)	0.0791 (12)	0.0208 (9)	0.0047 (9)	0.0049 (9)
C12	0.0558 (9)	0.0864 (14)	0.0574 (9)	−0.0123 (9)	−0.0032 (7)	−0.0049 (9)
C5	0.0469 (8)	0.0582 (9)	0.0607 (9)	0.0055 (7)	0.0130 (7)	0.0011 (7)
C14	0.0698 (10)	0.0495 (9)	0.0685 (10)	−0.0057 (8)	0.0164 (8)	−0.0070 (7)
C1	0.0648 (10)	0.0535 (9)	0.0629 (10)	0.0099 (8)	0.0025 (8)	0.0056 (7)
C13	0.0704 (11)	0.0718 (12)	0.0676 (11)	−0.0228 (9)	0.0082 (9)	−0.0141 (9)

Geometric parameters (Å, º) top

S1—C9	1.6818 (17)	C7—H7A	0.9700
Cl1—C1	1.7402 (18)	C7—H7B	0.9700
O1—C8	1.216 (2)	C3—C2	1.381 (3)
O2—C15	1.371 (2)	C3—C4	1.385 (2)
O2—C16	1.425 (2)	C3—H3	0.9300
N3—C9	1.3325 (19)	C4—C5	1.390 (2)
N3—C10	1.4112 (19)	C6—C1	1.372 (2)
N3—H3N	0.813 (18)	C6—C5	1.379 (2)
C10—C11	1.385 (2)	C6—H6	0.9300
C10—C15	1.404 (2)	C2—C1	1.376 (3)
N2—C9	1.356 (2)	C2—H2	0.9300
N2—N1	1.3904 (19)	C16—H16A	0.9600
N2—H2N	0.865 (19)	C16—H16B	0.9600
N1—C8	1.358 (2)	C16—H16C	0.9600
N1—H1N	0.864 (18)	C12—C13	1.362 (3)
C11—C12	1.382 (3)	C12—H12	0.9300
C11—H11	0.9300	C5—H5	0.9300
C15—C14	1.376 (2)	C14—C13	1.385 (3)
C8—C7	1.507 (2)	C14—H14	0.9300
C7—C4	1.514 (2)	C13—H13	0.9300

C15—O2—C16	118.35 (13)	C2—C3—H3	119.5
C9—N3—C10	133.17 (14)	C4—C3—H3	119.5
C9—N3—H3N	114.5 (12)	C3—C4—C5	118.21 (15)
C10—N3—H3N	112.4 (12)	C3—C4—C7	119.99 (14)
C11—C10—C15	119.03 (15)	C5—C4—C7	121.68 (14)
C11—C10—N3	126.56 (15)	C1—C6—C5	119.34 (16)
C15—C10—N3	114.39 (13)	C1—C6—H6	120.3
C9—N2—N1	121.53 (13)	C5—C6—H6	120.3
C9—N2—H2N	120.1 (12)	C1—C2—C3	119.44 (16)
N1—N2—H2N	113.9 (12)	C1—C2—H2	120.3
C8—N1—N2	120.24 (13)	C3—C2—H2	120.3
C8—N1—H1N	121.5 (12)	O2—C16—H16A	109.5
N2—N1—H1N	114.1 (12)	O2—C16—H16B	109.5
C12—C11—C10	119.65 (17)	H16A—C16—H16B	109.5
C12—C11—H11	120.2	O2—C16—H16C	109.5
C10—C11—H11	120.2	H16A—C16—H16C	109.5
O2—C15—C14	125.36 (15)	H16B—C16—H16C	109.5
O2—C15—C10	114.23 (13)	C13—C12—C11	121.00 (17)
C14—C15—C10	120.41 (15)	C13—C12—H12	119.5
O1—C8—N1	121.95 (15)	C11—C12—H12	119.5
O1—C8—C7	123.79 (15)	C6—C5—C4	121.14 (15)
N1—C8—C7	114.24 (14)	C6—C5—H5	119.4
N3—C9—N2	115.13 (13)	C4—C5—H5	119.4
N3—C9—S1	127.65 (12)	C15—C14—C13	119.51 (17)
N2—C9—S1	117.18 (12)	C15—C14—H14	120.2
C8—C7—C4	113.66 (12)	C13—C14—H14	120.2
C8—C7—H7A	108.8	C6—C1—C2	120.84 (17)
C4—C7—H7A	108.8	C6—C1—Cl1	119.29 (14)
C8—C7—H7B	108.8	C2—C1—Cl1	119.85 (14)
C4—C7—H7B	108.8	C12—C13—C14	120.32 (17)
H7A—C7—H7B	107.7	C12—C13—H13	119.8
C2—C3—C4	121.00 (16)	C14—C13—H13	119.8

C9—N3—C10—C11	−5.4 (3)	N1—C8—C7—C4	104.59 (16)
C9—N3—C10—C15	175.82 (15)	C2—C3—C4—C5	1.5 (2)
C9—N2—N1—C8	89.78 (18)	C2—C3—C4—C7	−174.54 (16)
C15—C10—C11—C12	1.1 (2)	C8—C7—C4—C3	−131.06 (16)
N3—C10—C11—C12	−177.59 (15)	C8—C7—C4—C5	53.0 (2)
C16—O2—C15—C14	1.1 (2)	C4—C3—C2—C1	−1.1 (3)
C16—O2—C15—C10	−178.85 (14)	C10—C11—C12—C13	1.2 (3)
C11—C10—C15—O2	177.07 (13)	C1—C6—C5—C4	−0.6 (3)
N3—C10—C15—O2	−4.04 (19)	C3—C4—C5—C6	−0.7 (2)
C11—C10—C15—C14	−2.8 (2)	C7—C4—C5—C6	175.30 (15)
N3—C10—C15—C14	176.04 (14)	O2—C15—C14—C13	−177.68 (15)
N2—N1—C8—O1	−12.7 (2)	C10—C15—C14—C13	2.2 (2)
N2—N1—C8—C7	168.94 (13)	C5—C6—C1—C2	1.1 (3)
C10—N3—C9—N2	176.74 (15)	C5—C6—C1—Cl1	−177.63 (14)
C10—N3—C9—S1	−1.1 (3)	C3—C2—C1—C6	−0.3 (3)
N1—N2—C9—N3	9.1 (2)	C3—C2—C1—Cl1	178.43 (14)
N1—N2—C9—S1	−172.85 (11)	C11—C12—C13—C14	−1.8 (3)
O1—C8—C7—C4	−73.8 (2)	C15—C14—C13—C12	0.1 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···S1ⁱ	0.862 (18)	2.435 (18)	3.269 (3)	163.1 (16)
N2—H2N···O1ⁱⁱ	0.865 (19)	2.159 (18)	2.941 (3)	150.1 (16)
N3—H3N···O2	0.810 (18)	2.099 (17)	2.551 (3)	115.2 (15)
N3—H3N···N1	0.810 (18)	2.229 (17)	2.656 (3)	113.3 (14)
C11—H11···S1	0.93	2.61	3.261 (3)	128

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

Experimental details

Crystal data
Chemical formula	C₁₆H₁₆ClN₃O₂S
M_r	349.83
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	293
a, b, c (Å)	5.935 (5), 16.970 (5), 17.038 (5)
β (°)	98.948 (5)
V (Å³)	1695.1 (16)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.36
Crystal size (mm)	0.36 × 0.31 × 0.21

Data collection
Diffractometer	Bruker APEXII
Absorption correction	Multi-scan (SADABS; Sheldrick, 1996)
T_min, T_max	0.881, 0.928
No. of measured, independent and observed [I > 2σ(I)] reflections	10318, 4083, 3190
R_int	0.020
(sin θ/λ)_max (Å⁻¹)	0.667

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.040, 0.111, 1.04
No. of reflections	4083
No. of parameters	221
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.24, −0.34

Computer programs: SMART (Bruker, 1998), SAINT (Bruker, 1997), SAINT, SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL (Bruker, 1997), SHELXTL, PARST (Nardelli, 1995) and PLATON (Spek, 2003).