Crystal structure of a new monoclinic polymorph of 2,4-dihydroxybenzaldehyde 4-methylthiosemicarbazone

A new monoclinic (P21/c) polymorph of the title compound has the same overall conformation as a previously reported (Cc) form with the exception of the conformation of the outer hydroxy H atom. This difference results in very different crystal packing based on hydrogen bonding, i.e. supramolecular tubes in the new form as opposed to a three-dimensional architecture in the Cc form.


Chemical context
In a review of the biological applications of metal complexes of thiosemicarbazone derivatives, Dilworth & Hueting (2012) highlighted the various biological roles exhibited by this class of compound. Thus, these may have therapeutic potential, for example being cytotoxic and capable of inhibiting both ribonuclease reductase and topoisomerase II. Metal complexes of thiosemicarbazones can also function as diagnostic agents in imaging/diagnostic applications. In the context of this biological relevance, the specific title compound of the present report has been coordinated as an N,O,S-tridentate dianion to zinc(II) and the resultant complex explored for activity against prostate cancer (Tan et al., 2012).
The crystal structure of the title molecule has been reported previously as a Cc polymorph (Tan et al., 2008b). Following on from previous structural work on related compounds (Affan et al., 2013), the title compound was prepared and routine screening of the crystals indicated that this crystallizes as a second monoclinic (P2 1 /c) polymorph. The crystal and mol- ISSN 2056-9890 ecular structure of the second form of the title compound is reported herein and compared with the original Cc polymorph.

Structural commentary
The molecular structure found in the new monoclinic (P2 1 /c) polymorph is shown in Fig. 1. The molecule is non-planar with a twist about the C1-N2 bond being evident as seen in (i) the N3-N2-C1-S1 torsion angle of 164.83 (11) and (ii) the dihedral angle between the N 3 CS residue (r.m.s. deviation = 0.0816 Å ) and benzene ring of 21.36 (4) . The conformation about the C3 N3 bond [1.292 (2) Å ] is E, the two N-bound H atoms are anti, and within the molecule, both the O1-and N1bound H atoms form intramolecular hydrogen bonds to the imine-N3 atom, Table 1. The O2-H2o H atom is approximately syn to the C6-H6 H atom.
To a first approximation, the molecular structure found in the Cc polymorph (Tan et al., 2008b), reported to be isolated also from an ethanol solution, is similar, but two significant differences are noted. These are highlighted in the overlay diagram shown in Fig. 2. With the N3-N2-C1-S1 torsion angle being À172.5 (2) , the twist about the C1-N2 bond deviates by about 8 , toward planarity, from that in the P2 1 /c form. However, the dihedral angle between the N 3 CS residue and benzene ring of 23.1 (9) is a little wider in the Cc form as the terminal methyl group is slightly twisted out of the CN 3 S plane: the C2-N1-C1-S1 torsion angle is À3.1 (5) cf. to 1.2 (2) in the P2 1 /c form. The major and most significant difference arises in the relative orientation of the outer hydroxy group where the H2o atom is anti to the C6-H6 H atom cf. approximately syn in the P2 1 /c form. This has a major consequence upon the crystal packing in the two forms as discussed in x3.
The calculated density for the P2 1 /c form is 1.496 g cm À3 and the packing efficiency (KPI), calculated by PLATON (Spek, 2009), is 73.1%. These values are lower than the comparable values in the Cc form, i.e. 1.521 g cm À3 and 74.4%, respectively, suggesting that the Cc form is the more stable.

Supramolecular features
In the crystal packing of the P2 1 /c polymorph, conventional hydrogen bonding interactions lead to the formation of a supramolecular tube, Fig. 3 and Table 1. Here, the inner N2-H2n atom forms a hydrogen bond to a translationally related inner O1 atom, and the bifurcated S1 atom accepts hydrogen bonds from the outer, centrosymmetically related, O2-H2o and a translationally related, outer N1-H1n atom. The tubes are aligned along the b axis and pack with no specific intermolecular interactions between them, Fig. 4. A distinctive crystal packing pattern is noted in the Cc polymorph (Tan et al., 2008b). Here, the inner N2-H2n atom forms a hydrogen bond to a glide-related inner O1 atom, leading to a supramolecular layer that stacks along the a axis. The S1 atoms project to one side of the layer and the outer O2-H2o atoms, The molecular structure of the title compound in the P2 1 /c polymorph, showing the atom labelling and displacement ellipsoids at the 70% probability level.

Figure 3
Supramolecular tube along the b axis in the structure of the P2 1 /c polymorph sustained by N-HÁ Á ÁO, O-HÁ Á ÁS and N-HÁ Á ÁS hydrogen bonds, shown as blue, orange and brown dashed lines, respectively (see Table 1 for details).
with the anti disposition (see above), lie to the other. These form hydrogen bonds so that a three-dimensional architecture ensues, Fig. 5. In this scenario, the outer N1-H1n atom only participates in an intramolecular hydrogen bond to the N3 atom, as does in the inner O1-H1o atom.

Database survey
Given the interest in semithiocarbazones owing to their biological potential, it is not surprising that a search of Version 5.35 (plus May updates) of the Cambridge Crystallographic Database (Groom & Allen, 2014) revealed almost 100 hits for the CC(H) NN(H)C( S)N(H)C fragment. The only restriction in the search was that the heaviest atom be S. In the absence of this restriction there were nearly 400 hits. Of the smaller set of structures, there was only one pair of polymorphs, namely two triclinic (P1) forms for salicylaldehyde 4phenylthiosemicarbazone, one with Z 0 = 3 (Seena et al., 2008) and the other with Z 0 = 2 (Rubčić et al., 2008). The most closely related structure in the literature is the N-Et derivative, reported twice (Tan et al., 2008a;Hussein et al., 2014). This structure exhibits the same molecular attributes as described above for the N-Me polymorphs, i.e. conformation, relative disposition of key atoms and intramolecular hydrogen bonding.

Special details
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.