Crystal structure of N-(4-hydroxybenzyl)acetone thiosemicarbazone

The inclusion of a methylene group at the thioamidic N atom of the acetone thiosemicarbazone derivative endows the molecule with greater flexibility and different pathways of association compared to those usually observed in the crystalline structures of these compounds.


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 (Nuñ ez- 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 Nuñ ez-Montenegro et al., 2014). In the present paper, we describe the synthesis and crystal structure 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 -CH 2group provides more flexibility to establish intermolecular associations.

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 -delocation (r.m.s. deviation of 0.0516 Å for the plane defined by atoms S1/C1/N1/N2/N3). ISSN 2056-9890 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 N1Á Á ÁN3 interaction [2.6074 (18) Å ] suggests some kind of intramolecular interaction.

Supramolecular features
The association of the molecules is strongly affected by the donor-acceptor character of the -OH group, while the usual N-HÁ Á ÁS hydrogen bonds observed in most TSC structures (Nuñ ez-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-H0Á Á ÁS1 iii ; Table 1), while the N2-H group establishes two different hydrogen-bonding interactions with different phenolic Oatom acceptors. The shortest of these is N2-H2Á Á ÁO i (Table 1), which generates a centrosymmetric cyclic R 2 2 (4) ring-motif association (Etter, 1990) and also forms a conjoined cyclic R 2 2 (6) association via an O-HÁ Á ÁS interaction (see Fig. 3). The second of the three-centre hydrogen-bonding interactions (N2-H2Á Á ÁO ii ) extends the structure into onedimensional duplex chains along [111] (Fig. 3).  Reaction scheme for the synthesis of acTSC.

Figure 2
The molecular structure of acTSC, with displacement ellipsoids drawn at the 40% probability level.

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%

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. Interactive H atoms on O and N atoms were located in difference Fourier analyses and were allowed to freely refine, with U iso (H) = 1.2U eq (O,N) and riding. Other H atoms were included at calculated sites and allowed to ride, with U iso (H) = 1.2U eq (aromatic and methylene C) or 1.5U eq (methyl C).   Special details 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.