Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270105037728/sf1021sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270105037728/sf1021Isup2.hkl |
CCDC reference: 296338
A solution of 2-hydroxy-1,2-diphenylethanone (benzoin) (2.122 g, 10 mmol) and 4-ethylthiosemicarbazide (1.192 g, 10 mmol) in absolute ethanol (50 ml) was refluxed in the presence of p-toluenesulfonic acid as catalyst (0.005 g) with continuous stirring. The course of the reaction was monitored by IR spectroscopy. On cooling to room temperature, the target product was precipitated with the slow addition of water, filtered, washed with copious cold ethanol and dried in air. Shiny crystals of (I) suitable for X-ray analysis were obtained by slow evaporation from an alcoholic [Ethanolic?] solution (yield 2.65 g, 84.6%; m.p. 434 K). Spectroscopic analysis: IR (Medium?, ν, cm-1): 3415 (–OH), 3337 and 3291 (–NH–), 1600 (C═N); 1H NMR (CDCl3, TMS, δ, p.p.m.): 1.19 (t, J = 6.95 Hz, 3H, –CH3), 3.63 (m, 2H, –CH2–), 6.08 (s, 1H, >CH–), 6.23 (s, 1H, –OH), 7.19–7.62 (m, 13H, aromatics plus –NH–), 11.83 (s, 1H, –NH–, D2O exchangeable); 13C NMR (CDCl3, TMS, δ, p.p.m): 14.65 (C1), 39.44 (C2), 176.71 (C3), 149.08 (C4), 136.80 (C5), 129.75 (C6), 128.55 (C7), 130.47 (C8), 75.34 (C9), 149.07 (C10), 127.15 (C11), 128.81 (C12), 127.36 (C13).
H atoms were positioned geometrically and refined with a riding model, fixing the bond lengths at 0.98, 0.97, 0.96, 0.93, 0.86 and 0.82 Å for CH, CH2, CH3, CH(aromatic), NH and OH, respectively. The displacement parameters of the H atoms were constrained as Uiso(H) = 1.2Ueq(parent), or 1.5Ueq(C) for methyl H atoms. Refinement of the absolute structure parameter (Flack, 1983) yielded a value of -0.12 (10). While the standard uncertainty in the Flack parameter is large, it is very likely that the chirality assigned is correct.
Recently, there has been considerable interest in the coordination chemistry of thiosemicarbazones because of their biological and carcinostatic activities (Liu, Lin et al., 1995; Lukevics et al., 1996) and their non-linear optical properties (Tian et al., 1997; Liu et al., 1999). These biological activities include antitumour and antileukaemic properties (French & Blanz, 1966; Agarwal et al., 1972), antibacterial and antiviral activities (Nandi et al., 1986; Chattopadhyay et al., 1987), infertility properties (Nagarajan et al., 1984), and anticancer (Ali & Livingstone, 1974) and antimalarial activities (Klayman et al., 1979). These properties are thought to arise from the metal-chelating ability of these ligands. In almost all cases, the ligands are bidentate and bind to the metal through the S and hydrazinic N atoms, although there are examples of them acting as monodentate ligands binding only through S (Valdes-Martines et al., 1996). It has been postulated that extensive electron delocalization in the thiosemicarbazone moiety helps the free thiosemicarbazone ligands and their metal complexes to exhibit SHG (second-harmonic generation) efficiency (Tian et al., 1997; Liu et al., 1999).
Due to its critical role in DNA synthesis and proliferation, iron is a potential target for the treatment of cancer (Richardson, 2002). To this end, the cellular antiproliferative effects of a number of iron-specific chelators and their complexes have been examined. A class of chelators with pronounced and selective activity against tumour cells are the thiosemicarbazones. The antitumour properties of heterocyclic thiosemicarbazones are partly related to their ability to inhibit the ribonucleoside diphosphate reductase enzyme (Cory et al., 1995; Liu, Lin & Sartorelli, 1995), which is essential in DNA synthesis (Moore et al., 1970). The mechanism by which these compounds act is still not well understood, but chelation of intracellular Fe and other metal ions is believed to be important. As part of our study of thiosemicarbazone derivatives, the title compound, (I), was prepared and the crystal structure determined in order to establish the conformational features of various functional groups, and also to compare the values obtained with reported structural results.
The molecular structure of (I), together with the atom-labelling scheme and the intramolecular hydrogen bonding, is shown in Fig. 1. As seen from the structure of the molecule, chirality is present around atom C5. In the crystallization procedure, only one enantiomer of the molecule has been crystallized. The thiosemicarbazone moiety shows an E configuration about both the C2—N2 and C1—N1 bonds, as found previously (Mathew & Palenik, 1971; Tian, Wu et al., 1999; Tian, Yu et al., 1999). The C—S bond distance of 1.691 (3) Å agrees well with similar bonds in related compounds, being intermediate between 1.82 Å for a C—S single bond and 1.56 Å for a C═S double bond (Wu et al., 2000). The corresponding C2—N2 bond distance of 1.356 (3) Å is indicative of some double-bond character, suggesting extensive electron delocalization in the whole molecule. It has been reported (Tian et al., 1997; Liu et al., 1999) that this type of structure helps thiosemicarbazone complexes to exhibit SHG efficiency. In this case, the noncentrosymmetry of the space group can allow the compound to exhibit SHG efficiency. The C2—N3 bond distance of 1.330 (4) Å is also indicative of some double-bond character. The C2—S1 and C2—N2 bond lengths indicate intermediate character between thione and thiol structures. The bond lengths of the thiosemicarbazone moiety (Table 1) show resonance character when compared with typical single- and double-bond lengths in cyclohexanone thiosemicarbazone (Casas et al., 2001). Atoms C1, N1, N2, C2, N3 and S1 are coplanar [the maximum deviation from the plane is -0.0499 (19) Å [For which atom?] and this clearly supports the resonance effect in this moiety.
The C6–C11 (A) and C12–C17 (B) phenyl rings are planar and are oriented at angles of 82.34 (8) and 8.07 (17)°, respectively, to the plane of the thiosemicarbazone moiety. These values indicate that the plane of the thiosemicarbazone moiety is almost parallel to the plane of ring B, while it is almost perpendicular to the plane of ring A. However, the four-membered bridge linking the phenyl rings to each other is not planar; the ΦCC torsion angle (C6—C5—C1—C12) is 101.3 (2)°, showing that the conformation about the C1—C5 bond is (+)anticlinal. The plane of ring A is nearly perpendicular to that of ring B, the corresponding dihedral angle being 79.87 (9)°. The greatest deviation from an ideal trigonal–planar geometry is at atom C1, where steric repulsion between the phenyl-methanol group and the phenyl ring contracts the N1—C1—C12 angle to 115.3 (2)°. In addition, the N2—C2—N3 angle [116.8 (3)°] indicates that there is also steric repulsion between the ethyl group and the thiocarbonyl S atom.
The potential donors N2 and O1 are found in a syn disposition, as a result of an intramolecular hydrogen bond [H2N···O1 = 2.10 and N2···O1 = 2.705 (3) Å]. Typically for this type of molecule, the S and hydrazinic N atoms are mutually trans, which allows for a weak intramolecular hydrogen bond between atoms N3 and N1 [H3N···N1 = 2.22 and N3···N1 = 2.626 (3) Å, and N3—H3N···N1 = 108.5°]. Such contacts have been observed in other derivatives (Park & Ahn, 1985; Parsons et al., 2000). The first of these intramolecular interactions leads to the formation of a six-membered ring, while the second leads to the formation of a five-membered ring which is fused with the six-membered ring (Fig. 1). Although the five-membered ring is close to being planar, with a maximum deviation of 0.0338 (15) Å for atom C2, the six-membered ring is not, the maximum deviation being 0.3545 (15) Å for atom O1.
Molecules of the title compound are packed in columns running along the a axis. The molecules in each column are connected to each other in a zigzag arrangement by means of linear O—H···S hydrogen bonds and C—H···π(benzene) interactions (Fig. 2 and Table 2). In these C—H···π interactions, atom C13 forms a C—H···π contact with the centroid, Cg1, of the C6–C11 ring of the molecule at position (x + 1, y, z). In addition, there are also C—H···π(benzene) interactions between the columns. In these C—H···π interactions, atom C9 forms a C—H···π contact with the centroid, Cg2, of the C12–C17 ring of the molecule at position (1 - x, 1/2 + y, -z). Although N—H···S-type hydrogen bonds leading to the formation of dimers are a common feature previously observed in similar thiosemicarbazone compounds (Palenik et al., 1974; Restivo & Palenik, 1970; Dinçer et al., 2005), this type of interaction is not observed in the crystal structure of (I). The full geometry of the intra- and intermolecular interactions is given in Table 2. There are no other significant interactions, such as π–π stacking, in the crystal structure.
Data collection: X-AREA (Stoe & Cie, 2002); cell refinement: X-AREA; data reduction: X-RED32 (Stoe & Cie, 2002); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: OTREP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999) and PLATON (Spek, 2003).
C17H19N3OS | F(000) = 332 |
Mr = 313.41 | Dx = 1.240 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2yb | Cell parameters from 18162 reflections |
a = 5.5803 (3) Å | θ = 2.4–27.9° |
b = 11.5739 (10) Å | µ = 0.20 mm−1 |
c = 13.1420 (8) Å | T = 296 K |
β = 98.660 (5)° | Rod, colourless |
V = 839.11 (10) Å3 | 0.80 × 0.42 × 0.16 mm |
Z = 2 |
Stoe IPDS-2 diffractometer | 3958 independent reflections |
Radiation source: sealed X-ray tube, 12 x 0.4 mm long-fine focus | 2723 reflections with I > 2σ(I) |
Plane graphite monochromator | Rint = 0.095 |
Detector resolution: 6.67 pixels mm-1 | θmax = 27.8°, θmin = 2.4° |
ω scans | h = −7→7 |
Absorption correction: integration (X-RED32; Stoe & Cie, 2002) | k = −15→15 |
Tmin = 0.864, Tmax = 0.968 | l = −17→17 |
14309 measured reflections |
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)] = 0.048 | H-atom parameters constrained |
wR(F2) = 0.135 | w = 1/[σ2(Fo2) + (0.0682P)2] where P = (Fo2 + 2Fc2)/3 |
S = 1.02 | (Δ/σ)max < 0.001 |
3958 reflections | Δρmax = 0.35 e Å−3 |
193 parameters | Δρmin = −0.24 e Å−3 |
1 restraint | Absolute structure: Flack (1983), with how many Friedel pairs |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: −0.12 (10) |
C17H19N3OS | V = 839.11 (10) Å3 |
Mr = 313.41 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 5.5803 (3) Å | µ = 0.20 mm−1 |
b = 11.5739 (10) Å | T = 296 K |
c = 13.1420 (8) Å | 0.80 × 0.42 × 0.16 mm |
β = 98.660 (5)° |
Stoe IPDS-2 diffractometer | 3958 independent reflections |
Absorption correction: integration (X-RED32; Stoe & Cie, 2002) | 2723 reflections with I > 2σ(I) |
Tmin = 0.864, Tmax = 0.968 | Rint = 0.095 |
14309 measured reflections |
R[F2 > 2σ(F2)] = 0.048 | H-atom parameters constrained |
wR(F2) = 0.135 | Δρmax = 0.35 e Å−3 |
S = 1.02 | Δρmin = −0.24 e Å−3 |
3958 reflections | Absolute structure: Flack (1983), with how many Friedel pairs |
193 parameters | Absolute structure parameter: −0.12 (10) |
1 restraint |
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. |
x | y | z | Uiso*/Ueq | ||
S1 | 0.25501 (14) | 0.47167 (7) | 0.45274 (7) | 0.0794 (3) | |
O1 | 0.8517 (3) | 0.49564 (17) | 0.25301 (17) | 0.0716 (5) | |
H1 | 0.9684 | 0.4947 | 0.2991 | 0.107* | |
N1 | 0.7012 (4) | 0.27297 (19) | 0.33281 (17) | 0.0545 (5) | |
N2 | 0.5566 (4) | 0.3641 (2) | 0.35079 (18) | 0.0603 (5) | |
H2N | 0.5574 | 0.4268 | 0.3157 | 0.072* | |
N3 | 0.3995 (5) | 0.2502 (3) | 0.4667 (2) | 0.0810 (6) | |
H3N | 0.4970 | 0.1984 | 0.4500 | 0.097* | |
C1 | 0.8368 (4) | 0.2838 (2) | 0.26239 (19) | 0.0515 (5) | |
C2 | 0.4123 (5) | 0.3541 (3) | 0.4246 (2) | 0.0615 (6) | |
C3 | 0.2341 (6) | 0.2141 (3) | 0.5399 (3) | 0.0810 (6) | |
H3A | 0.0800 | 0.2538 | 0.5233 | 0.097* | |
H3B | 0.2044 | 0.1317 | 0.5338 | 0.097* | |
C4 | 0.3428 (10) | 0.2419 (4) | 0.6448 (3) | 0.1108 (13) | |
H4A | 0.2350 | 0.2189 | 0.6916 | 0.166* | |
H4B | 0.3712 | 0.3236 | 0.6506 | 0.166* | |
H4C | 0.4938 | 0.2014 | 0.6613 | 0.166* | |
C5 | 0.8461 (4) | 0.3916 (2) | 0.1954 (2) | 0.0566 (6) | |
H5 | 0.9942 | 0.3878 | 0.1638 | 0.068* | |
C6 | 0.6308 (5) | 0.3937 (2) | 0.1098 (2) | 0.0612 (6) | |
C7 | 0.4549 (5) | 0.4798 (3) | 0.1052 (3) | 0.0775 (8) | |
H7 | 0.4672 | 0.5375 | 0.1549 | 0.093* | |
C8 | 0.2606 (6) | 0.4784 (4) | 0.0251 (4) | 0.0962 (12) | |
H8 | 0.1438 | 0.5362 | 0.0210 | 0.115* | |
C9 | 0.2397 (7) | 0.3935 (5) | −0.0472 (3) | 0.1060 (16) | |
H9 | 0.1073 | 0.3932 | −0.0994 | 0.127* | |
C10 | 0.4116 (7) | 0.3083 (4) | −0.0440 (3) | 0.0969 (12) | |
H10 | 0.3979 | 0.2505 | −0.0937 | 0.116* | |
C11 | 0.6072 (6) | 0.3103 (3) | 0.0355 (2) | 0.0741 (8) | |
H11 | 0.7252 | 0.2533 | 0.0379 | 0.089* | |
C12 | 0.9929 (4) | 0.1818 (2) | 0.2484 (2) | 0.0494 (5) | |
C13 | 1.1594 (5) | 0.1825 (2) | 0.1804 (2) | 0.0608 (6) | |
H13 | 1.1716 | 0.2470 | 0.1394 | 0.073* | |
C14 | 1.3084 (5) | 0.0879 (3) | 0.1726 (2) | 0.0691 (8) | |
H14 | 1.4194 | 0.0897 | 0.1264 | 0.083* | |
C15 | 1.2939 (5) | −0.0068 (3) | 0.2313 (2) | 0.0718 (8) | |
H15 | 1.3947 | −0.0697 | 0.2255 | 0.086* | |
C16 | 1.1293 (6) | −0.0102 (3) | 0.3002 (2) | 0.0733 (7) | |
H16 | 1.1204 | −0.0751 | 0.3412 | 0.088* | |
C17 | 0.9779 (5) | 0.0830 (2) | 0.3077 (2) | 0.0630 (7) | |
H17 | 0.8647 | 0.0796 | 0.3528 | 0.076* |
U11 | U22 | U33 | U12 | U13 | U23 | |
S1 | 0.0761 (4) | 0.0861 (6) | 0.0792 (5) | 0.0173 (4) | 0.0216 (3) | −0.0167 (4) |
O1 | 0.0782 (11) | 0.0463 (10) | 0.0911 (14) | 0.0004 (9) | 0.0155 (10) | −0.0025 (9) |
N1 | 0.0533 (10) | 0.0556 (12) | 0.0555 (12) | 0.0051 (9) | 0.0111 (9) | −0.0015 (10) |
N2 | 0.0635 (11) | 0.0553 (12) | 0.0664 (14) | 0.0089 (10) | 0.0237 (11) | 0.0005 (10) |
N3 | 0.0910 (13) | 0.0836 (14) | 0.0745 (13) | 0.0006 (11) | 0.0326 (10) | 0.0022 (10) |
C1 | 0.0477 (11) | 0.0546 (14) | 0.0531 (14) | −0.0011 (10) | 0.0108 (10) | 0.0002 (10) |
C2 | 0.0575 (13) | 0.0713 (16) | 0.0561 (15) | 0.0072 (12) | 0.0101 (12) | −0.0074 (13) |
C3 | 0.0910 (13) | 0.0836 (14) | 0.0745 (13) | 0.0006 (11) | 0.0326 (10) | 0.0022 (10) |
C4 | 0.143 (3) | 0.093 (3) | 0.096 (3) | −0.018 (3) | 0.017 (3) | −0.009 (2) |
C5 | 0.0523 (12) | 0.0520 (13) | 0.0686 (16) | 0.0025 (11) | 0.0197 (11) | 0.0091 (12) |
C6 | 0.0570 (13) | 0.0622 (15) | 0.0679 (16) | 0.0030 (12) | 0.0204 (12) | 0.0212 (13) |
C7 | 0.0687 (16) | 0.0711 (19) | 0.097 (2) | 0.0115 (15) | 0.0260 (15) | 0.0314 (19) |
C8 | 0.0698 (18) | 0.104 (3) | 0.115 (3) | 0.012 (2) | 0.0154 (19) | 0.055 (3) |
C9 | 0.080 (2) | 0.158 (5) | 0.077 (2) | −0.006 (3) | −0.0009 (19) | 0.053 (3) |
C10 | 0.089 (2) | 0.138 (4) | 0.062 (2) | 0.001 (2) | 0.0042 (17) | 0.018 (2) |
C11 | 0.0742 (17) | 0.088 (2) | 0.0613 (18) | 0.0064 (15) | 0.0144 (14) | 0.0121 (15) |
C12 | 0.0471 (11) | 0.0499 (12) | 0.0514 (12) | −0.0010 (9) | 0.0074 (9) | −0.0023 (9) |
C13 | 0.0554 (12) | 0.0575 (15) | 0.0733 (17) | 0.0047 (11) | 0.0219 (12) | 0.0099 (12) |
C14 | 0.0587 (14) | 0.0712 (18) | 0.082 (2) | 0.0099 (13) | 0.0253 (14) | 0.0011 (15) |
C15 | 0.0666 (14) | 0.0652 (18) | 0.082 (2) | 0.0165 (14) | 0.0074 (13) | −0.0058 (16) |
C16 | 0.0920 (18) | 0.0564 (16) | 0.0722 (18) | 0.0127 (15) | 0.0145 (15) | 0.0066 (14) |
C17 | 0.0714 (15) | 0.0569 (15) | 0.0641 (16) | 0.0042 (12) | 0.0216 (13) | 0.0018 (12) |
S1—C2 | 1.691 (3) | C6—C7 | 1.394 (4) |
O1—C5 | 1.421 (3) | C7—C8 | 1.393 (5) |
O1—H1 | 0.8200 | C7—H7 | 0.9300 |
N1—C1 | 1.287 (3) | C8—C9 | 1.359 (7) |
N1—N2 | 1.370 (3) | C8—H8 | 0.9300 |
N2—C2 | 1.356 (3) | C9—C10 | 1.372 (7) |
N2—H2N | 0.8600 | C9—H9 | 0.9300 |
N3—C2 | 1.330 (4) | C10—C11 | 1.392 (5) |
N3—C3 | 1.489 (4) | C10—H10 | 0.9300 |
N3—H3N | 0.8600 | C11—H11 | 0.9300 |
C1—C12 | 1.495 (3) | C12—C13 | 1.383 (4) |
C1—C5 | 1.532 (3) | C12—C17 | 1.393 (4) |
C3—C4 | 1.456 (5) | C13—C14 | 1.388 (4) |
C3—H3A | 0.9700 | C13—H13 | 0.9300 |
C3—H3B | 0.9700 | C14—C15 | 1.349 (5) |
C4—H4A | 0.9600 | C14—H14 | 0.9300 |
C4—H4B | 0.9600 | C15—C16 | 1.384 (4) |
C4—H4C | 0.9600 | C15—H15 | 0.9300 |
C5—C6 | 1.517 (4) | C16—C17 | 1.383 (4) |
C5—H5 | 0.9800 | C16—H16 | 0.9300 |
C6—C11 | 1.365 (5) | C17—H17 | 0.9300 |
C5—O1—H1 | 109.5 | C7—C6—C5 | 121.2 (3) |
C1—N1—N2 | 118.3 (2) | C8—C7—C6 | 119.2 (4) |
C2—N2—N1 | 119.1 (2) | C8—C7—H7 | 120.4 |
C2—N2—H2N | 120.5 | C6—C7—H7 | 120.4 |
N1—N2—H2N | 120.5 | C9—C8—C7 | 120.8 (4) |
C2—N3—C3 | 126.8 (3) | C9—C8—H8 | 119.6 |
C2—N3—H3N | 116.6 | C7—C8—H8 | 119.6 |
C3—N3—H3N | 116.6 | C8—C9—C10 | 120.8 (4) |
N1—C1—C12 | 115.3 (2) | C8—C9—H9 | 119.6 |
N1—C1—C5 | 124.6 (2) | C10—C9—H9 | 119.6 |
C12—C1—C5 | 120.1 (2) | C9—C10—C11 | 118.4 (4) |
N3—C2—N2 | 116.8 (3) | C9—C10—H10 | 120.8 |
N3—C2—S1 | 125.0 (2) | C11—C10—H10 | 120.8 |
N2—C2—S1 | 118.1 (2) | C6—C11—C10 | 122.0 (3) |
C4—C3—N3 | 109.8 (3) | C6—C11—H11 | 119.0 |
C4—C3—H3A | 109.7 | C10—C11—H11 | 119.0 |
N3—C3—H3A | 109.7 | C13—C12—C17 | 117.9 (2) |
C4—C3—H3B | 109.7 | C13—C12—C1 | 122.4 (2) |
N3—C3—H3B | 109.7 | C17—C12—C1 | 119.6 (2) |
H3A—C3—H3B | 108.2 | C12—C13—C14 | 120.8 (3) |
C3—C4—H4A | 109.5 | C12—C13—H13 | 119.6 |
C3—C4—H4B | 109.5 | C14—C13—H13 | 119.6 |
H4A—C4—H4B | 109.5 | C15—C14—C13 | 120.7 (3) |
C3—C4—H4C | 109.5 | C15—C14—H14 | 119.7 |
H4A—C4—H4C | 109.5 | C13—C14—H14 | 119.7 |
H4B—C4—H4C | 109.5 | C14—C15—C16 | 120.0 (3) |
O1—C5—C6 | 109.4 (2) | C14—C15—H15 | 120.0 |
O1—C5—C1 | 112.6 (2) | C16—C15—H15 | 120.0 |
C6—C5—C1 | 110.3 (2) | C17—C16—C15 | 119.8 (3) |
O1—C5—H5 | 108.1 | C17—C16—H16 | 120.1 |
C6—C5—H5 | 108.1 | C15—C16—H16 | 120.1 |
C1—C5—H5 | 108.1 | C16—C17—C12 | 120.8 (3) |
C11—C6—C7 | 118.8 (3) | C16—C17—H17 | 119.6 |
C11—C6—C5 | 120.0 (3) | C12—C17—H17 | 119.6 |
C1—N1—N2—C2 | 179.9 (2) | C6—C7—C8—C9 | 0.9 (4) |
N2—N1—C1—C12 | 178.9 (2) | C7—C8—C9—C10 | −1.1 (5) |
N2—N1—C1—C5 | −0.9 (4) | C8—C9—C10—C11 | 0.5 (5) |
C3—N3—C2—N2 | −172.6 (3) | C7—C6—C11—C10 | −0.7 (4) |
C3—N3—C2—S1 | 4.9 (5) | C5—C6—C11—C10 | 179.5 (3) |
N1—N2—C2—N3 | −7.8 (4) | C9—C10—C11—C6 | 0.5 (5) |
N1—N2—C2—S1 | 174.54 (18) | N1—C1—C12—C13 | −176.0 (3) |
C2—N3—C3—C4 | −86.3 (4) | C5—C1—C12—C13 | 3.8 (4) |
N1—C1—C5—O1 | 43.6 (3) | N1—C1—C12—C17 | 2.1 (3) |
C12—C1—C5—O1 | −136.2 (2) | C5—C1—C12—C17 | −178.1 (2) |
N1—C1—C5—C6 | −78.9 (3) | C17—C12—C13—C14 | −0.8 (4) |
C12—C1—C5—C6 | 101.3 (2) | C1—C12—C13—C14 | 177.3 (2) |
O1—C5—C6—C11 | 170.8 (2) | C12—C13—C14—C15 | 0.0 (5) |
C1—C5—C6—C11 | −64.9 (3) | C13—C14—C15—C16 | 0.0 (5) |
O1—C5—C6—C7 | −9.1 (3) | C14—C15—C16—C17 | 0.7 (5) |
C1—C5—C6—C7 | 115.3 (3) | C15—C16—C17—C12 | −1.6 (4) |
C11—C6—C7—C8 | 0.0 (4) | C13—C12—C17—C16 | 1.6 (4) |
C5—C6—C7—C8 | 179.9 (3) | C1—C12—C17—C16 | −176.6 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2N···O1 | 0.86 | 2.10 | 2.705 (3) | 127 |
N3—H3N···N1 | 0.86 | 2.22 | 2.626 (3) | 109 |
O1—H1···S1i | 0.82 | 2.39 | 3.202 (2) | 168 |
Symmetry code: (i) x+1, y, z. |
Experimental details
Crystal data | |
Chemical formula | C17H19N3OS |
Mr | 313.41 |
Crystal system, space group | Monoclinic, P21 |
Temperature (K) | 296 |
a, b, c (Å) | 5.5803 (3), 11.5739 (10), 13.1420 (8) |
β (°) | 98.660 (5) |
V (Å3) | 839.11 (10) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.20 |
Crystal size (mm) | 0.80 × 0.42 × 0.16 |
Data collection | |
Diffractometer | Stoe IPDS2 |
Absorption correction | Integration (X-RED32; Stoe & Cie, 2002) |
Tmin, Tmax | 0.864, 0.968 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 14309, 3958, 2723 |
Rint | 0.095 |
(sin θ/λ)max (Å−1) | 0.657 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.048, 0.135, 1.02 |
No. of reflections | 3958 |
No. of parameters | 193 |
No. of restraints | 1 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.35, −0.24 |
Absolute structure | Flack (1983), with how many Friedel pairs |
Absolute structure parameter | −0.12 (10) |
Computer programs: X-AREA (Stoe & Cie, 2002), X-AREA, X-RED32 (Stoe & Cie, 2002), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), OTREP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999) and PLATON (Spek, 2003).
O1—C5 | 1.421 (3) | C1—C12 | 1.495 (3) |
N1—C1 | 1.287 (3) | C1—C5 | 1.532 (3) |
N1—N2 | 1.370 (3) | C3—C4 | 1.456 (5) |
N3—C3 | 1.489 (4) | C5—C6 | 1.517 (4) |
C1—N1—N2 | 118.3 (2) | O1—C5—C6 | 109.4 (2) |
C2—N2—N1 | 119.1 (2) | O1—C5—C1 | 112.6 (2) |
C2—N3—C3 | 126.8 (3) | C6—C5—C1 | 110.3 (2) |
N1—C1—C5 | 124.6 (2) | C11—C6—C5 | 120.0 (3) |
N3—C2—S1 | 125.0 (2) | C7—C6—C5 | 121.2 (3) |
N2—C2—S1 | 118.1 (2) | C13—C12—C1 | 122.4 (2) |
C4—C3—N3 | 109.8 (3) | C17—C12—C1 | 119.6 (2) |
C1—N1—N2—C2 | 179.9 (2) | C3—N3—C2—S1 | 4.9 (5) |
N2—N1—C1—C12 | 178.9 (2) | N1—N2—C2—N3 | −7.8 (4) |
N2—N1—C1—C5 | −0.9 (4) | N1—N2—C2—S1 | 174.54 (18) |
C3—N3—C2—N2 | −172.6 (3) | C2—N3—C3—C4 | −86.3 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2N···O1 | 0.86 | 2.10 | 2.705 (3) | 127 |
N3—H3N···N1 | 0.86 | 2.22 | 2.626 (3) | 109 |
O1—H1···S1i | 0.82 | 2.39 | 3.202 (2) | 168 |
Symmetry code: (i) x+1, y, z. |
Recently, there has been considerable interest in the coordination chemistry of thiosemicarbazones because of their biological and carcinostatic activities (Liu, Lin et al., 1995; Lukevics et al., 1996) and their non-linear optical properties (Tian et al., 1997; Liu et al., 1999). These biological activities include antitumour and antileukaemic properties (French & Blanz, 1966; Agarwal et al., 1972), antibacterial and antiviral activities (Nandi et al., 1986; Chattopadhyay et al., 1987), infertility properties (Nagarajan et al., 1984), and anticancer (Ali & Livingstone, 1974) and antimalarial activities (Klayman et al., 1979). These properties are thought to arise from the metal-chelating ability of these ligands. In almost all cases, the ligands are bidentate and bind to the metal through the S and hydrazinic N atoms, although there are examples of them acting as monodentate ligands binding only through S (Valdes-Martines et al., 1996). It has been postulated that extensive electron delocalization in the thiosemicarbazone moiety helps the free thiosemicarbazone ligands and their metal complexes to exhibit SHG (second-harmonic generation) efficiency (Tian et al., 1997; Liu et al., 1999).
Due to its critical role in DNA synthesis and proliferation, iron is a potential target for the treatment of cancer (Richardson, 2002). To this end, the cellular antiproliferative effects of a number of iron-specific chelators and their complexes have been examined. A class of chelators with pronounced and selective activity against tumour cells are the thiosemicarbazones. The antitumour properties of heterocyclic thiosemicarbazones are partly related to their ability to inhibit the ribonucleoside diphosphate reductase enzyme (Cory et al., 1995; Liu, Lin & Sartorelli, 1995), which is essential in DNA synthesis (Moore et al., 1970). The mechanism by which these compounds act is still not well understood, but chelation of intracellular Fe and other metal ions is believed to be important. As part of our study of thiosemicarbazone derivatives, the title compound, (I), was prepared and the crystal structure determined in order to establish the conformational features of various functional groups, and also to compare the values obtained with reported structural results.
The molecular structure of (I), together with the atom-labelling scheme and the intramolecular hydrogen bonding, is shown in Fig. 1. As seen from the structure of the molecule, chirality is present around atom C5. In the crystallization procedure, only one enantiomer of the molecule has been crystallized. The thiosemicarbazone moiety shows an E configuration about both the C2—N2 and C1—N1 bonds, as found previously (Mathew & Palenik, 1971; Tian, Wu et al., 1999; Tian, Yu et al., 1999). The C—S bond distance of 1.691 (3) Å agrees well with similar bonds in related compounds, being intermediate between 1.82 Å for a C—S single bond and 1.56 Å for a C═S double bond (Wu et al., 2000). The corresponding C2—N2 bond distance of 1.356 (3) Å is indicative of some double-bond character, suggesting extensive electron delocalization in the whole molecule. It has been reported (Tian et al., 1997; Liu et al., 1999) that this type of structure helps thiosemicarbazone complexes to exhibit SHG efficiency. In this case, the noncentrosymmetry of the space group can allow the compound to exhibit SHG efficiency. The C2—N3 bond distance of 1.330 (4) Å is also indicative of some double-bond character. The C2—S1 and C2—N2 bond lengths indicate intermediate character between thione and thiol structures. The bond lengths of the thiosemicarbazone moiety (Table 1) show resonance character when compared with typical single- and double-bond lengths in cyclohexanone thiosemicarbazone (Casas et al., 2001). Atoms C1, N1, N2, C2, N3 and S1 are coplanar [the maximum deviation from the plane is -0.0499 (19) Å [For which atom?] and this clearly supports the resonance effect in this moiety.
The C6–C11 (A) and C12–C17 (B) phenyl rings are planar and are oriented at angles of 82.34 (8) and 8.07 (17)°, respectively, to the plane of the thiosemicarbazone moiety. These values indicate that the plane of the thiosemicarbazone moiety is almost parallel to the plane of ring B, while it is almost perpendicular to the plane of ring A. However, the four-membered bridge linking the phenyl rings to each other is not planar; the ΦCC torsion angle (C6—C5—C1—C12) is 101.3 (2)°, showing that the conformation about the C1—C5 bond is (+)anticlinal. The plane of ring A is nearly perpendicular to that of ring B, the corresponding dihedral angle being 79.87 (9)°. The greatest deviation from an ideal trigonal–planar geometry is at atom C1, where steric repulsion between the phenyl-methanol group and the phenyl ring contracts the N1—C1—C12 angle to 115.3 (2)°. In addition, the N2—C2—N3 angle [116.8 (3)°] indicates that there is also steric repulsion between the ethyl group and the thiocarbonyl S atom.
The potential donors N2 and O1 are found in a syn disposition, as a result of an intramolecular hydrogen bond [H2N···O1 = 2.10 and N2···O1 = 2.705 (3) Å]. Typically for this type of molecule, the S and hydrazinic N atoms are mutually trans, which allows for a weak intramolecular hydrogen bond between atoms N3 and N1 [H3N···N1 = 2.22 and N3···N1 = 2.626 (3) Å, and N3—H3N···N1 = 108.5°]. Such contacts have been observed in other derivatives (Park & Ahn, 1985; Parsons et al., 2000). The first of these intramolecular interactions leads to the formation of a six-membered ring, while the second leads to the formation of a five-membered ring which is fused with the six-membered ring (Fig. 1). Although the five-membered ring is close to being planar, with a maximum deviation of 0.0338 (15) Å for atom C2, the six-membered ring is not, the maximum deviation being 0.3545 (15) Å for atom O1.
Molecules of the title compound are packed in columns running along the a axis. The molecules in each column are connected to each other in a zigzag arrangement by means of linear O—H···S hydrogen bonds and C—H···π(benzene) interactions (Fig. 2 and Table 2). In these C—H···π interactions, atom C13 forms a C—H···π contact with the centroid, Cg1, of the C6–C11 ring of the molecule at position (x + 1, y, z). In addition, there are also C—H···π(benzene) interactions between the columns. In these C—H···π interactions, atom C9 forms a C—H···π contact with the centroid, Cg2, of the C12–C17 ring of the molecule at position (1 - x, 1/2 + y, -z). Although N—H···S-type hydrogen bonds leading to the formation of dimers are a common feature previously observed in similar thiosemicarbazone compounds (Palenik et al., 1974; Restivo & Palenik, 1970; Dinçer et al., 2005), this type of interaction is not observed in the crystal structure of (I). The full geometry of the intra- and intermolecular interactions is given in Table 2. There are no other significant interactions, such as π–π stacking, in the crystal structure.