research communications
N-(4-hydroxybenzyl)acetone thiosemicarbazone
ofaDepartamento de Química Inorgánica, Facultade de Química, Instituto de Investigación Sanitaria Galicia Sur – Universidade de Vigo, Campus Universitario, E-36310 Vigo, Galicia, Spain
*Correspondence e-mail: ezequiel@uvigo.es
The structure of the title compound, C11H15N3OS, shows the flexibility due to the methylene group at the thioamide N atom in the side chain, resulting in the molecule being non-planar. The dihedral angle between the plane of the benzene ring and that defined by the atoms of the thiosemicarbazide arm is 79.847 (4)°. In the crystal, the donor–acceptor hydrogen-bond character of the –OH group dominates the intermolecular associations, acting as a donor in an O—H⋯S hydrogen bond, as well as being a double acceptor in a centrosymmetric cyclic bridging N—H⋯O,O′ interaction [graph set R22(4)]. The result is a one-dimensional duplex chain structure, extending along [111]. The usual N—H⋯S hydrogen-bonding association common in thiosemicarbazone crystal structures is not observed.
Keywords: crystal structure; thiosemicarbazone; thiourea; hydrogen bonding.
CCDC reference: 1570200
1. Chemical context
Thiosemicarbazones (TSCs) are an interesting group of compounds because they show diverse biological properties (Serda et al., 2012) and pharmacological activities (Lukmantara et al., 2013). They can be easily functionalized to yield different supramolecular arrays through intermolecular hydrogen-bonding interactions (Nuñez-Montenegro et al., 2017), by selection of suitable aldehyde or ketone reagents. In addition, metal coordination may be used to orient some of their substituents to optimize the interaction with biomolecules (e.g. see Nuñez-Montenegro et al., 2014). In the present paper, we describe the synthesis and of a TSC derivative (Figs. 1), namely N-(4-hydroxybenzyl)acetone thiosemicarbazone (acTSC), having a 4-hydroxybenzyl substituent at the thioamide N atom (N1), in which the –CH2– group provides more flexibility to establish intermolecular associations.
2. Structural commentary
In the acTSC molecule (Fig. 2), the bond lengths (S1=C1 and C10=N3) and angles in the thiosemicarbazide arm are similar to those observed in other thiosemicarbazones, suggesting that the thione form is predominant. This arm is almost planar, probably due to some π-delocation (r.m.s. deviation of 0.0516 Å for the plane defined by atoms S1/C1/N1/N2/N3). Nevertheless, the ethylene group at N1 allows an almost orthogonal orientation relative to the phenolic substituent group, with a dihedral angle between the two planes of 79.847 (4)°. The interatomic distance N1⋯N3 interaction [2.6074 (18) Å] suggests some kind of intramolecular interaction.
3. Supramolecular features
The association of the molecules is strongly affected by the donor–acceptor character of the –OH group, while the usual N—H⋯S hydrogen bonds observed in most TSC structures (Nuñez-Montenegro et al., 2017; Pino-Cuevas et al., 2014) are absent. The phenolic –OH group forms an intermolecular hydrogen bond with a S-atom acceptor (O—H0⋯S1iii; Table 1), while the N2—H group establishes two different hydrogen-bonding interactions with different phenolic O-atom acceptors. The shortest of these is N2—H2⋯Oi (Table 1), which generates a centrosymmetric cyclic R22(4) ring-motif association (Etter, 1990) and also forms a conjoined cyclic R22(6) association via an O—H⋯S interaction (see Fig. 3). The second of the three-centre hydrogen-bonding interactions (N2—H2⋯Oii) extends the structure into one-dimensional duplex chains along [111] (Fig. 3).
4. Database survey
For related structures of thiosemicarbazones derived from acetone, see: Yamin et al. (2014); Basu & Das (2011); Venkatraman et al. (2005); Jian et al. (2005). For the metal-coordination properties of thiosemicarbazones, see: Paterson & Donnelly (2011); Casas et al. (2000). For acetone derivatives, see, for example, Su et al. (2013); Nuñez-Montenegro et al. (2014); Swesi et al. (2006); Paek et al. (1997).
5. Synthesis and crystallization
The reaction scheme for the synthesis of the title compound is shown in Fig. 1. The primary amine 4-hydroxybenzylamine was converted to the corresponding isothiocyanate by reaction with thiophosgene (Sharma, 1978). This isothiocyanate was treated with hydrazide to form the thiosemicarbazide, as described previously (Reis et al., 2011). Finally, this compound was reacted with acetone in order to synthesize the desired thiosemicarbazone. In a typical synthesis, 3.4 g (0.017 mol) of thiosemicarbazide was dissolved in acetone (20 ml) and heated to 60°C for 20 min (Fig. 1). This solution was concentrated and the resultant residue was purified using a silica column (AcOEt–hexane 30%). This solution was vacuum dried giving 1.96 g of acTSC. The solution was also used to obtain single crystals by slow evaporation (yield 48%; m.p. 165°C). C11H15N3OS requires: C 55.7, H 6.4, N 17.7%; found C 55.8, H 7.1,N 16.9%. MS–ESI [m/z (%)]: 238 (100) [M + H]+. IR (ATR, ν/cm−1): 3241 (b) ν(NH, OH); 1536 (w), 1508 (s) ν(C=N); 784 (w) ν(C=S). 1H NMR (DMSO-d6): 9.95 (s, 1H, N2H), 9.26 (s, 1H, OH), 8.46 (t, 3JH-NH = 6.2Hz, 1H, N1H), 7.15 (d, 3JH-H = 8.5Hz, 2H, C5H, C9H), 6.70 (d, 3JH-H = 8.5Hz, 2H, C6H, C8H), 4.65 (d, 3JH-H = 6.2Hz, 2H, C3H), 1.92 (d, 3JH-H = 8.5Hz, 6H, C11H, C12H).
6. Refinement
Crystal data, data collection and structure . Interactive H atoms on O and N atoms were located in difference Fourier analyses and were allowed to freely refine, with Uiso(H) = 1.2Ueq(O,N) and riding. Other H atoms were included at calculated sites and allowed to ride, with Uiso(H) = 1.2Ueq(aromatic and methylene C) or 1.5Ueq(methyl C).
details are summarized in Table 2Supporting information
CCDC reference: 1570200
https://doi.org/10.1107/S2056989017012129/zs2385sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989017012129/zs2385Isup2.hkl
Data collection: APEX3 (Bruker, 2014); cell
SAINT (Bruker, 2014); data reduction: SAINT (Bruker, 2014); program(s) used to solve structure: SHELXS2013 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2015b); molecular graphics: Mercury (Bruno et al., 2002); software used to prepare material for publication: SHELXL2013 (Sheldrick, 2015b).C11H15N3OS | F(000) = 252 |
Mr = 237.32 | Dx = 1.339 Mg m−3 |
Triclinic, P1 | Melting point: 438 K |
a = 8.2799 (8) Å | Mo Kα radiation, λ = 0.71073 Å |
b = 8.9169 (9) Å | Cell parameters from 9917 reflections |
c = 9.7451 (10) Å | θ = 2.5–28.3° |
α = 104.597 (3)° | µ = 0.26 mm−1 |
β = 112.569 (3)° | T = 100 K |
γ = 105.220 (3)° | Prism, colourless |
V = 588.7 (1) Å3 | 0.18 × 0.11 × 0.11 mm |
Z = 2 |
Bruker D8 Venture Photon 100 CMOS diffractometer | 2562 reflections with I > 2σ(I) |
φ and ω scans | Rint = 0.043 |
Absorption correction: multi-scan (SADABS; Bruker, 2014) | θmax = 28.3°, θmin = 2.5° |
Tmin = 0.638, Tmax = 0.746 | h = −11→11 |
17083 measured reflections | k = −11→11 |
2911 independent reflections | l = −12→13 |
Refinement on F2 | 0 restraints |
Least-squares matrix: full | Hydrogen site location: mixed |
R[F2 > 2σ(F2)] = 0.032 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.082 | w = 1/[σ2(Fo2) + (0.0325P)2 + 0.3538P] where P = (Fo2 + 2Fc2)/3 |
S = 1.00 | (Δ/σ)max < 0.001 |
2911 reflections | Δρmax = 0.29 e Å−3 |
156 parameters | Δρmin = −0.28 e Å−3 |
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. |
x | y | z | Uiso*/Ueq | ||
C12 | 0.5032 (2) | −0.1953 (2) | 0.3563 (2) | 0.0345 (4) | |
H12A | 0.6301 | −0.1042 | 0.4309 | 0.052* | |
H12B | 0.5165 | −0.2971 | 0.3036 | 0.052* | |
H12C | 0.4356 | −0.2199 | 0.4166 | 0.052* | |
C11 | 0.1912 (2) | −0.26338 (16) | 0.10998 (17) | 0.0243 (3) | |
H11A | 0.1070 | −0.2506 | 0.1562 | 0.036* | |
H11B | 0.1842 | −0.3793 | 0.0828 | 0.036* | |
H11C | 0.1508 | −0.2401 | 0.0118 | 0.036* | |
S1 | 0.33739 (4) | 0.28903 (4) | 0.00401 (4) | 0.02014 (10) | |
O | 0.96910 (14) | 0.95385 (12) | 0.83590 (11) | 0.0206 (2) | |
H0 | 1.063 (3) | 1.046 (2) | 0.864 (2) | 0.031* | |
N2 | 0.37419 (16) | 0.05734 (13) | 0.12372 (13) | 0.0170 (2) | |
H2 | 0.254 (2) | 0.024 (2) | 0.0853 (19) | 0.020* | |
N1 | 0.65479 (15) | 0.27673 (13) | 0.21157 (13) | 0.0163 (2) | |
H1 | 0.701 (2) | 0.225 (2) | 0.2663 (19) | 0.020* | |
N3 | 0.47907 (15) | 0.00499 (14) | 0.23774 (13) | 0.0194 (2) | |
C6 | 0.79084 (18) | 0.67223 (16) | 0.64146 (15) | 0.0173 (2) | |
H6 | 0.7308 | 0.6484 | 0.7038 | 0.021* | |
C3 | 0.77639 (18) | 0.44581 (15) | 0.24342 (15) | 0.0171 (2) | |
H3A | 0.7100 | 0.4789 | 0.1551 | 0.021* | |
H3B | 0.8951 | 0.4438 | 0.2427 | 0.021* | |
C1 | 0.46524 (17) | 0.20611 (15) | 0.12097 (14) | 0.0147 (2) | |
C4 | 0.82883 (17) | 0.57817 (15) | 0.40388 (14) | 0.0148 (2) | |
C7 | 0.92864 (17) | 0.83296 (15) | 0.69457 (14) | 0.0158 (2) | |
C9 | 0.96926 (17) | 0.73918 (15) | 0.46107 (15) | 0.0170 (2) | |
H9 | 1.0319 | 0.7622 | 0.4003 | 0.020* | |
C8 | 1.01956 (17) | 0.86683 (15) | 0.60508 (15) | 0.0164 (2) | |
H8 | 1.1150 | 0.9760 | 0.6419 | 0.020* | |
C5 | 0.74164 (17) | 0.54680 (15) | 0.49646 (15) | 0.0162 (2) | |
H5 | 0.6466 | 0.4376 | 0.4600 | 0.019* | |
C10 | 0.39253 (19) | −0.14134 (17) | 0.23078 (16) | 0.0197 (3) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C12 | 0.0274 (8) | 0.0421 (9) | 0.0502 (10) | 0.0188 (7) | 0.0187 (7) | 0.0374 (8) |
C11 | 0.0297 (7) | 0.0153 (6) | 0.0263 (7) | 0.0065 (5) | 0.0131 (6) | 0.0090 (5) |
S1 | 0.01646 (16) | 0.01708 (15) | 0.02248 (17) | 0.00497 (12) | 0.00379 (13) | 0.01202 (12) |
O | 0.0182 (5) | 0.0184 (4) | 0.0173 (4) | 0.0022 (4) | 0.0071 (4) | 0.0030 (4) |
N2 | 0.0138 (5) | 0.0164 (5) | 0.0197 (5) | 0.0056 (4) | 0.0053 (4) | 0.0104 (4) |
N1 | 0.0152 (5) | 0.0145 (5) | 0.0182 (5) | 0.0059 (4) | 0.0059 (4) | 0.0083 (4) |
N3 | 0.0174 (5) | 0.0228 (5) | 0.0238 (6) | 0.0108 (4) | 0.0097 (5) | 0.0157 (5) |
C6 | 0.0154 (6) | 0.0201 (6) | 0.0178 (6) | 0.0059 (5) | 0.0085 (5) | 0.0101 (5) |
C3 | 0.0151 (6) | 0.0164 (6) | 0.0187 (6) | 0.0042 (5) | 0.0081 (5) | 0.0076 (5) |
C1 | 0.0163 (6) | 0.0135 (5) | 0.0139 (5) | 0.0060 (5) | 0.0075 (5) | 0.0046 (4) |
C4 | 0.0131 (5) | 0.0158 (5) | 0.0161 (6) | 0.0072 (5) | 0.0055 (5) | 0.0082 (5) |
C7 | 0.0134 (5) | 0.0169 (6) | 0.0144 (6) | 0.0067 (5) | 0.0036 (5) | 0.0065 (4) |
C9 | 0.0154 (6) | 0.0182 (6) | 0.0202 (6) | 0.0065 (5) | 0.0094 (5) | 0.0110 (5) |
C8 | 0.0131 (5) | 0.0146 (5) | 0.0194 (6) | 0.0041 (4) | 0.0056 (5) | 0.0086 (5) |
C5 | 0.0131 (5) | 0.0154 (5) | 0.0186 (6) | 0.0042 (4) | 0.0060 (5) | 0.0087 (5) |
C10 | 0.0213 (6) | 0.0225 (6) | 0.0263 (7) | 0.0131 (5) | 0.0155 (5) | 0.0152 (5) |
S1—C1 | 1.6959 (14) | C8—C9 | 1.3914 (18) |
O—C7 | 1.3708 (16) | C10—C11 | 1.498 (2) |
O—H0 | 0.86 (2) | C10—C12 | 1.495 (2) |
N1—C3 | 1.4527 (19) | C3—H3A | 0.9900 |
N1—C1 | 1.3328 (19) | C3—H3B | 0.9900 |
N2—N3 | 1.3929 (17) | C5—H5 | 0.9500 |
N2—C1 | 1.3554 (19) | C6—H6 | 0.9500 |
N3—C10 | 1.284 (2) | C8—H8 | 0.9500 |
N1—H1 | 0.839 (18) | C9—H9 | 0.9500 |
N2—H2 | 0.849 (18) | C11—H11A | 0.9800 |
C3—C4 | 1.5186 (18) | C11—H11B | 0.9800 |
C4—C5 | 1.391 (2) | C11—H11C | 0.9800 |
C4—C9 | 1.395 (2) | C12—H12A | 0.9800 |
C5—C6 | 1.3914 (19) | C12—H12B | 0.9800 |
C6—C7 | 1.392 (2) | C12—H12C | 0.9800 |
C7—C8 | 1.391 (2) | ||
C7—O—H0 | 111.1 (13) | N1—C3—H3B | 109.00 |
C1—N1—C3 | 124.73 (12) | C4—C3—H3A | 109.00 |
N2—N3—C10 | 116.82 (12) | C4—C3—H3B | 109.00 |
S1—C1—N1 | 124.19 (11) | H3A—C3—H3B | 108.00 |
S1—C1—N2 | 119.75 (11) | C4—C5—H5 | 119.00 |
C1—N1—H1 | 115.1 (12) | C6—C5—H5 | 119.00 |
C3—N1—H1 | 119.1 (12) | C5—C6—H6 | 120.00 |
N1—C1—N2 | 116.05 (12) | C7—C6—H6 | 120.00 |
N3—N2—H2 | 120.9 (12) | C7—C8—H8 | 120.00 |
C1—N2—H2 | 116.2 (13) | C9—C8—H8 | 120.00 |
N1—C3—C4 | 113.39 (12) | C4—C9—H9 | 119.00 |
C3—C4—C5 | 122.91 (12) | C8—C9—H9 | 119.00 |
C5—C4—C9 | 118.17 (12) | C10—C11—H11A | 109.00 |
C3—C4—C9 | 118.92 (12) | C10—C11—H11B | 109.00 |
C4—C5—C6 | 121.31 (13) | C10—C11—H11C | 109.00 |
C5—C6—C7 | 119.54 (13) | H11A—C11—H11B | 109.00 |
O—C7—C6 | 117.57 (13) | H11A—C11—H11C | 109.00 |
C6—C7—C8 | 120.21 (12) | H11B—C11—H11C | 109.00 |
O—C7—C8 | 122.21 (12) | C10—C12—H12A | 109.00 |
C7—C8—C9 | 119.30 (13) | C10—C12—H12B | 109.00 |
C4—C9—C8 | 121.46 (13) | C10—C12—H12C | 109.00 |
N3—C10—C12 | 116.82 (14) | H12A—C12—H12B | 109.00 |
C11—C10—C12 | 116.61 (14) | H12A—C12—H12C | 109.00 |
N3—C10—C11 | 126.57 (13) | H12B—C12—H12C | 109.00 |
N1—C3—H3A | 109.00 | ||
C3—N1—C1—S1 | 10.03 (19) | C3—C4—C9—C8 | 178.25 (13) |
C3—N1—C1—N2 | −171.02 (12) | C3—C4—C5—C6 | −178.75 (14) |
C1—N1—C3—C4 | 97.14 (15) | C9—C4—C5—C6 | 0.6 (2) |
C1—N2—N3—C10 | −175.62 (14) | C5—C4—C9—C8 | −1.1 (2) |
N3—N2—C1—S1 | −170.98 (10) | C4—C5—C6—C7 | 0.7 (2) |
N3—N2—C1—N1 | 10.02 (19) | C5—C6—C7—C8 | −1.4 (2) |
N2—N3—C10—C12 | −178.18 (13) | C5—C6—C7—O | 178.34 (13) |
N2—N3—C10—C11 | 1.5 (2) | O—C7—C8—C9 | −178.83 (13) |
N1—C3—C4—C9 | 169.60 (13) | C6—C7—C8—C9 | 0.9 (2) |
N1—C3—C4—C5 | −11.0 (2) | C7—C8—C9—C4 | 0.4 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2···Oi | 0.848 (17) | 2.292 (17) | 2.9955 (15) | 140.6 (14) |
N2—H2···Oii | 0.848 (17) | 2.434 (16) | 3.1333 (15) | 140.3 (14) |
O—H0···S1iii | 0.857 (19) | 2.299 (19) | 3.1349 (10) | 165.2 (16) |
Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) x−1, y−1, z−1; (iii) x+1, y+1, z+1. |
Funding information
Funding for this research was provided by: Ministry of Economy, Industry and Competitiveness (Spain) and European Regional Development Fund (EU) (CTQ2015-71211-REDT and CTQ2015-7091-R).
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