4-(3-Fluoro­phen­yl)-1-(propan-2-yl­idene)thio­semicarbazone

Abstract

The title compound, C₁₀H₁₂FN₃S, crystallizes in the same space group (P2₁/c) as two polymorphic forms of 4-phenyl-1-(propan-2-yl­idene)thio­semicarbazone [Jian et al. (2005). Acta Cryst. E61, o653–o654; Venkatraman et al. (2005). Acta Cryst. E61, o3914–o3916]. The arrangement of mol­ecules relative to the twofold screw axes is similar to that in the crystal structure of the lower density polymorph. In the solid state, the mol­ecular conformation is stabilized by an intra­molecular N—H⋯N hydrogen bond. The mol­ecules form centrosymmetric R ₂ ²(8) dimers in the crystal through pairs of N—H⋯S hydrogen bonds.

Related literature

For related structures, see: Basu & Das (2011 ▶); Park & Ahn (1985 ▶); Parsons et al. (2000 ▶); Jian et al. (2005 ▶); Venkatraman et al. (2005 ▶). For description of the Cambridge Structural Database, see: Allen (2002 ▶). For the anti­tumor, anti­viral and anti­fungal activity of thio­semicarbazones, see: Kalinowski et al. (2009 ▶); Smee & Sidwell (2003 ▶); Beraldo & Gambino (2004 ▶). For their metal-chelating properties, see: Paterson & Donnelly (2011 ▶); Casas et al. (2000 ▶).

Experimental

Crystal data

• C₁₀H₁₂FN₃S

• M _r = 225.29

• Monoclinic,

• a = 9.038 (2) Å

• b = 10.515 (2) Å

• c = 11.869 (2) Å

• β = 99.77 (3)°

• V = 1111.6 (4) ų

• Z = 4

• Cu Kα radiation

• μ = 2.48 mm⁻¹

• T = 296 K

• 0.55 × 0.30 × 0.10 mm

Data collection

• Kuma KM-4 diffractometer

• Absorption correction: for a cylinder mounted on the ϕ axis (Dwiggins, 1975 ▶) T _min = 0.435, T _max = 0.485

• 3800 measured reflections

• 1942 independent reflections

• 1252 reflections with I > 2σ(I)

• R _int = 0.084

• 3 standard reflections every 100 reflections intensity decay: 3.3%

Refinement

• R[F ² > 2σ(F ²)] = 0.068

• wR(F ²) = 0.217

• S = 1.04

• 1942 reflections

• 138 parameters

• H-atom parameters constrained

• Δρ_max = 0.38 e Å⁻³

• Δρ_min = −0.39 e Å⁻³

Data collection: KM-4 Software (Kuma Diffraction, 1991 ▶); cell refinement: KM-4 Software; data reduction: KM-4 Software; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg, 1999 ▶), Mercury (Macrae et al., 2006 ▶) and ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Supplementary material file. DOI: 10.1107/S1600536811042504/fy2024Isup2.mol

Supplementary material file. DOI: 10.1107/S1600536811042504/fy2024Isup4.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯N3	0.86	2.12	2.553 (5)	111
N2—H2⋯S1i	0.86	2.67	3.465 (3)	154

Symmetry code: (i) .

supplementary crystallographic information

Comment

Thiosemicarbazones are widely studied due to their antitumor, antiviral and antifungal activity (Kalinowski et al., 2009; Smee & Sidwell, 2003; Beraldo & Gambino, 2004) as well as for their metal chelating properties (Paterson & Donnelly, 2011; Casas et al., 2000). The molecular structure of the title compound (I) with numbering scheme is shown in Fig. 1. Recently, two crystal forms of 4-phenyl-1-(propan-2-ylidene)thiosemicarbazone have been reported. However, they were not identified as polymorphs (Jian et al., 2005, CSD Refcode: FIDDUS; Venkatraman et al., 2005, Refcode: FIDDUS01). Crystals of FIDDUS were obtained by recrystallisation from dimethyl sulfoxide, while those of FIDDUS01 from an acetone:methanol solution. The crystal structure reported here is similar to the lower density polymorph, FIDDUS (d = 1.258 Mg/m^-3vs. 1.302 Mg/m^-3 for FIDDUS01).

The bond lengths confirm the thione form of the title molecule, the presence of a double bond between the N3 and C2 atoms, and they indicate some π-delocalisation along the thiosemicarbazone fragment. The S1 and the hydrazinic N3 atoms are in the trans conformation with the S1—C1—N2—N3 torsion angle equal to -177.7 (3)°. This conformation enables the formation of an intramolecular N1—H···N3 hydrogen bond. Consequently, the thiosemicarbazone part of the molecule (N1—C1—S1—N2—N3) is planar, with the maximum deviation from the mean plane of these atoms being 0.014 (2) Å for N3. This conformation seems to be characteristic of the thiosemicarbazone fragment, and it is observed in all related crystal structures found in the CSD (Allen, 2002) [Refcodes: CUZXOK (Parsons et al., 2000), DAWPOG (Park & Ahn, 1985), FIDDUS (Jian et al., 2005), FIDDUS01 (Venkatraman et al., 2005) and UQOWAZ (Basu & Das, 2011))]. The dihedral angles between the central thiosemicarbazone plane of (I) and the planes formed by the propan-2-ylidene (C2—C3—C4) and phenyl (C1P to C6P) groups are 16.7 (4) and 38.9 (2)°, respectively. For comparison, the respective angles in FIDDUS are 14.0° and 38.6°; and in FIDDUS01 they are 23.6° and 42.8°.

The thiosemicarbazone part is also involved in intermolecular (N2—H···S1) hydrogen bonds (Fig. 2, Table 1), resulting in R²₂(8) centrosymmetric dimers. (The same pattern have been found in DAWPOG, FIDDUS, FIDDUS01 and UQOWAZ.) The main difference between the two aforementioned polymorphs is the orientation of the molecules relative to the twofold screw axes. In FIDDUS and in (I) the 2₁ screw axis passes through the C1—N1 bond, while in FIDDUS01 it runs through the N2—N3 bond (Figs. 3 and 4). Additionally, in FIDDUS01 the thiosemicarbazone plane is almost perpendicular to the b direction (85.7°) while in FIDDDUS and in (I) the corresponding angles are 62.0° and 59.9 (4)°, respectively. In (I) and in FIDDUS there are offset stacking interactions between the aromatic rings (Fig. 3) with interplanar distances of 3.5 (1) Å and 3.6 Å, respectively. The physical consequence of these stacking interactions is the yellow colour of FIDDUS crystals, in contrast to the colourless crystals of FIDDUS01, where overlapping of the heteroatoms is observed (Fig. 4). Surprisingly, the crystals of (I) are colourless, despite the similar molecular and crystal structure with FIDDUS. This could be explained by the changes in the electronic structure of the aromatic ring in molecule (I) caused by the electronegative fluorine substituent. The presence of the fluorine atom in (I) causes only slight differences in crystal packing with respect to FIDDUS. In (I) there is a short intermolecular contact between the F1 and C2 (1 - x, 1/2 + y, 0.5 - z) atoms with a distance of 3.107 (5) Å (the sum of van der Waals radii is 3.17 Å).

Experimental

The title compound, C₁₀H₁₂FN₃S, was obtained in the reaction of 4-amino-1,7,8,9,10-pentamethyl-4-azatricyclo[2.5.1.0^2,6]dec-8-ene-3,5-dione and 3-fluorophenyl isothiocyanate in acetonitrile. The mixture of the reagents was refluxed for 6 h. After heating, the solvent was removed on a rotary evaporator. The residue was purified by column chromatography (chloroform:methanol 5.5:0.5). Two products were obtained in this reaction, viz.: 1-(3-fluorophenyl)-3-(1,7,8,9,10-pentametyl-3,5-dioxo-4-azatricyclo[5.2.1.0^2,6]dec-8-en-4-yl)thiourea (60%) and 4-(3-fluorophenyl)-1-(propan-2-ylidene)thiosemicarbazone (40%). The title compound was recrystallised from acetonitrile.

Refinement

All C-bonded H atoms were positioned geometrically and allowed to ride on the attached atom with C—H bond lengths of 0.93 Å for aromatic atoms and 0.96 Å for methyl groups. The positions of N-bonded H atoms were located in the difference electron density maps and then constrained with an N—H distance of 0.86 Å. U_iso(H) values were fixed to 1.2U_eq(C,N).

Figures

Fig. 1.

Molecular structure of the title compound with 50% probability displacement ellipsoids. H atoms are shown as small spheres of an arbitrary size. Thin single line represents the intramolecular hydrogen bond.

Fig. 2.

Dimer in (I) formed by hydrogen bonds around a centre of symmetry.

Fig. 3.

Orientation of molecules in relation to the 21 screw axes in (I). View along the b axis. Green symbols indicate the positions of 21 screw axes in the unit cells.

Fig. 4.

Orientation of molecules in relation to the 21 screw axes in FIDDUS01. View along b axis. Green symbols indicate positions of 21 screw axes in the unit cells.

Crystal data

C10H12FN3S	F(000) = 472
Mr = 225.29	Dx = 1.346 Mg m−3
Monoclinic, P21/c	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ybc	Cell parameters from 75 reflections
a = 9.038 (2) Å	θ = 6–20°
b = 10.515 (2) Å	µ = 2.48 mm−1
c = 11.869 (2) Å	T = 296 K
β = 99.77 (3)°	Plate, colourless
V = 1111.6 (4) Å3	0.55 × 0.30 × 0.10 mm
Z = 4

Data collection

Kuma KM-4 diffractometer	1252 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.084
graphite	θmax = 67.7°, θmin = 5.0°
ω–2θ scans	h = −10→10
Absorption correction: for a cylinder mounted on the φ axis (Dwiggins, 1975)	k = −12→12
Tmin = 0.435, Tmax = 0.485	l = 0→14
3800 measured reflections	3 standard reflections every 100 reflections
1942 independent reflections	intensity decay: 3.3%

Refinement

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)] = 0.068	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.217	H-atom parameters constrained
S = 1.04	w = 1/[σ2(Fo2) + (0.1522P)2] where P = (Fo2 + 2Fc2)/3
1942 reflections	(Δ/σ)max = 0.013
138 parameters	Δρmax = 0.38 e Å−3
0 restraints	Δρmin = −0.39 e Å−3

Special details

Experimental. cylinder dimensions used for absorption correction: 0.2 mm radius and a 0.1 mm height

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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
C1	0.4980 (4)	0.4433 (3)	0.2021 (3)	0.0493 (8)
C1P	0.3908 (4)	0.4006 (4)	0.3776 (3)	0.0506 (9)
C2	0.8673 (4)	0.3455 (4)	0.1991 (3)	0.0557 (9)
C2P	0.3249 (5)	0.5171 (4)	0.3911 (3)	0.0566 (9)
H2P	0.3381	0.5864	0.3451	0.068*
C3	0.9760 (5)	0.2575 (6)	0.2680 (4)	0.0785 (14)
H3A	0.9395	0.2344	0.3366	0.094*
H3B	1.0715	0.2989	0.2876	0.094*
H3C	0.9870	0.1823	0.2242	0.094*
C3P	0.2380 (5)	0.5252 (4)	0.4767 (4)	0.0613 (10)
C4	0.9221 (5)	0.4267 (5)	0.1128 (4)	0.0718 (13)
H4A	0.9086	0.3830	0.0408	0.086*
H4B	1.0268	0.4448	0.1373	0.086*
H5C	0.8665	0.5049	0.1046	0.086*
C4P	0.2123 (5)	0.4283 (5)	0.5460 (4)	0.0675 (11)
H4P	0.1521	0.4384	0.6015	0.081*
C5P	0.2802 (6)	0.3136 (5)	0.5299 (4)	0.0700 (12)
H5P	0.2662	0.2447	0.5761	0.084*
C6P	0.3682 (5)	0.2991 (4)	0.4467 (4)	0.0639 (11)
H6P	0.4124	0.2209	0.4370	0.077*
N1	0.4913 (4)	0.3838 (3)	0.3000 (3)	0.0564 (8)
H1	0.5586	0.3263	0.3189	0.068*
N2	0.6276 (4)	0.4233 (3)	0.1607 (3)	0.0560 (8)
H2	0.6427	0.4587	0.0983	0.067*
N3	0.7337 (4)	0.3444 (4)	0.2220 (3)	0.0567 (8)
S1	0.36293 (11)	0.53442 (10)	0.12753 (8)	0.0578 (4)
F1	0.1751 (4)	0.6403 (3)	0.4920 (3)	0.0941 (11)

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
C1	0.0477 (18)	0.0465 (19)	0.0519 (19)	0.0021 (16)	0.0037 (14)	−0.0012 (15)
C1P	0.0412 (17)	0.061 (2)	0.0499 (18)	0.0004 (16)	0.0070 (14)	0.0020 (16)
C2	0.052 (2)	0.057 (2)	0.058 (2)	0.0001 (18)	0.0065 (17)	−0.0026 (18)
C2P	0.063 (2)	0.052 (2)	0.055 (2)	0.0007 (18)	0.0113 (17)	0.0036 (17)
C3	0.062 (3)	0.099 (3)	0.073 (3)	0.027 (3)	0.006 (2)	0.007 (3)
C3P	0.072 (3)	0.061 (2)	0.0521 (19)	0.012 (2)	0.0145 (18)	−0.0026 (18)
C4	0.049 (2)	0.087 (3)	0.078 (3)	−0.008 (2)	0.0078 (19)	0.011 (3)
C4P	0.071 (3)	0.078 (3)	0.058 (2)	0.008 (2)	0.0247 (19)	0.007 (2)
C5P	0.075 (3)	0.071 (3)	0.068 (3)	0.001 (2)	0.026 (2)	0.016 (2)
C6P	0.068 (3)	0.057 (2)	0.067 (2)	0.006 (2)	0.0116 (19)	0.0073 (19)
N1	0.0545 (18)	0.0620 (19)	0.0541 (17)	0.0156 (16)	0.0133 (13)	0.0080 (15)
N2	0.0498 (17)	0.0609 (18)	0.0572 (18)	0.0055 (15)	0.0087 (13)	0.0070 (15)
N3	0.0502 (17)	0.064 (2)	0.0564 (17)	0.0092 (15)	0.0107 (14)	0.0049 (15)
S1	0.0535 (6)	0.0664 (7)	0.0528 (6)	0.0100 (5)	0.0069 (4)	0.0064 (4)
F1	0.139 (3)	0.0729 (18)	0.0802 (18)	0.0358 (19)	0.0475 (18)	0.0055 (15)

Geometric parameters (Å, °)

C1—N1	1.331 (5)	C3P—C4P	1.354 (6)
C1—N2	1.361 (5)	C3P—F1	1.362 (5)
C1—S1	1.681 (4)	C4—H4A	0.9600
C1P—C6P	1.382 (6)	C4—H4B	0.9600
C1P—C2P	1.383 (6)	C4—H5C	0.9600
C1P—N1	1.409 (5)	C4P—C5P	1.381 (7)
C2—N3	1.282 (5)	C4P—H4P	0.9300
C2—C4	1.482 (6)	C5P—C6P	1.377 (6)
C2—C3	1.489 (6)	C5P—H5P	0.9300
C2P—C3P	1.389 (6)	C6P—H6P	0.9300
C2P—H2P	0.9300	N1—H1	0.8600
C3—H3A	0.9600	N2—N3	1.379 (5)
C3—H3B	0.9600	N2—H2	0.8600
C3—H3C	0.9600
N1—C1—N2	114.4 (3)	C2—C4—H4B	109.5
N1—C1—S1	126.2 (3)	H4A—C4—H4B	109.5
N2—C1—S1	119.4 (3)	C2—C4—H5C	109.5
C6P—C1P—C2P	120.3 (4)	H4A—C4—H5C	109.5
C6P—C1P—N1	117.9 (4)	H4B—C4—H5C	109.5
C2P—C1P—N1	121.6 (4)	C3P—C4P—C5P	116.6 (4)
N3—C2—C4	126.1 (4)	C3P—C4P—H4P	121.7
N3—C2—C3	115.8 (4)	C5P—C4P—H4P	121.7
C4—C2—C3	118.1 (4)	C6P—C5P—C4P	121.3 (4)
C1P—C2P—C3P	116.6 (4)	C6P—C5P—H5P	119.3
C1P—C2P—H2P	121.7	C4P—C5P—H5P	119.3
C3P—C2P—H2P	121.7	C5P—C6P—C1P	120.1 (4)
C2—C3—H3A	109.5	C5P—C6P—H6P	119.9
C2—C3—H3B	109.5	C1P—C6P—H6P	119.9
H3A—C3—H3B	109.5	C1—N1—C1P	129.9 (3)
C2—C3—H3C	109.5	C1—N1—H1	115.0
H3A—C3—H3C	109.5	C1P—N1—H1	115.0
H3B—C3—H3C	109.5	C1—N2—N3	117.8 (3)
C4P—C3P—F1	118.1 (4)	C1—N2—H2	121.1
C4P—C3P—C2P	125.0 (4)	N3—N2—H2	121.1
F1—C3P—C2P	116.9 (4)	C2—N3—N2	118.6 (4)
C2—C4—H4A	109.5

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N3	0.86	2.12	2.553 (5)	111
N2—H2···S1i	0.86	2.67	3.465 (3)	154

Symmetry codes: (i) −x+1, −y+1, −z.