Crystal structures of (E)-4-[1-(2-carbamothioylhydrazinylidene)ethyl]phenyl acetate and (E)-4-[1-(2-carbamothioylhydrazinylidene)ethyl]phenyl benzoate

In the title compounds, the thiosemicarbazone group adopts an extended conformation, and there is a short N—H⋯N contact present forming an S(5) ring motif. In the crystals of both compounds, molecules are linked by pairs of N—H⋯S hydrogen bonds, forming dimers with (8) ring motifs.

In the title compounds, C 11 H 13 N 3 O 2 S, (I), and C 16 H 15 N 3 O 2 S, (II), the thiosemicarbazone group adopts an extended conformation. The acetate ester (I) crystallizes with two independent molecules in the asymmetric unit. In the benzoate ester (II), the planes of the two aryl rings are inclined to one another by 46.70 (7) . In both compounds, there is a short intramolecular N-HÁ Á ÁN contact present, forming an S(5) ring motif. In the crystals of both compounds, molecules are linked via pairs of N-HÁ Á ÁS hydrogen bonds, forming dimers with R 2 2 (8) ring motifs. The dimers are linked by N-HÁ Á ÁS and N-HÁ Á ÁO hydrogen bonds, forming slabs parallel to (011). In (I), there are N-HÁ Á Á and C-HÁ Á Á interactions present within the slabs, while in (II), there are only N-HÁ Á Á interactions present.

Chemical context
Thiosemicarbazones are potent intermediates for the synthesis of pharmaceutical and bioactive materials and they are used extensively in the field of medicinal chemistry. The biological activity of these ligands is related to their ability to coordinate to metal centres in enzymes (Seena et al., 2006). These derivatives possess an additional functional group that is not coordinated to their 'primary' metal ion, thereby suggesting that the biological activity may also depend on the non-coordinating groups (Venkatesh et al., 2016). Thiosemicarbazones in their neutral or deprotonated form behave as N,N,S-thiodentate chelates towards metal ions. They display antiproliferative activity on different tumors cell lines and have been a common feature of all compounds with carcinogenic potency. A strong correlation has been found between tumor growth rate and the ribonucleoside diphosphate reductase (RDR) enzyme (Arora et al., 2014).
Thiosemicarbazone derivatives have found applications in drug development for the treatment of central nervous system disorders and bacterial infection as well as being analgesic and anti-allergic agents. They are inhibitors of DNA replication and also of many proteases. This inhibitory activity explains the level of interest given to them in the fight against microbial and parasitic diseases (Mani et al., 2015). Thiosemicarbazones have many biological activities such as antiviral, antibacterial, antitumor, anti African trypanosome (Fatondji et al., 2013), antimicrobial, sodium channel blocker, anticancer, antitubercular, antiviral (Venkatesh et al., 2016), antifungal, ISSN 2056-9890 locomotor activity (Singh et al., 2011), antimalarial, anticancer and they are used as a cure for leprosy, rheumatism and trypanosomiasis (Parul et al., 2012). As part of our studies in this area, we now describe the syntheses and structures of the title compounds (I) and (II).

Figure 2
The molecular structure of the compound (II), showing the atom labelling and displacement ellipsoids drawn at the 40% probability level. The short intramolecular N-HÁ Á ÁN contact is shown as a dashed line (see Table 2). Table 1 Hydrogen-bond geometry (Å , ) for (I).

Supramolecular features
In the crystal of (I), the two molecules are linked by a pair of N-HÁ Á ÁS hydrogen bonds forming A-B dimers with an R 2 2 (8) ring motif. The dimers are linked by N-HÁ Á ÁS and N-HÁ Á ÁO hydrogen bonds, forming slabs lying parallel to (011), as shown in Table 1 and Fig. 3. Within the slabs there are N-HÁ Á Á and C-HÁ Á Á interactions present (Table 1).
In the crystal of (II), molecules are linked by pairs of N-HÁ Á ÁS hydrogen bonds, forming inversion dimers with an R 2 2 (8) ring motif (Table 2 and Fig. 4). As in the crystal of compound (I), the dimers are linked by N-HÁ Á ÁS and N-HÁ Á ÁO hydrogen bonds, forming slabs lying parallel to plane (011); see Table 2 and Fig. 4. Within the slabs, there are only N-HÁ Á Á interactions present (Table 2).

Database survey
A search of the Cambridge Structural Database (CSD, Version 5.37, last update May 2016; Groom et al., 2016) for the substructure 2-(1-phenylethylidene)hydrazine-1-carbothioamide yielded 100 hits. One of the compounds, (E)-4-(Ncarbamothioylethanehydrazonoyl)phenyl 4-methylbenzoate (NOVFOV; Mani et al., 2015) is the 4-methylbenzoate analogue of compound (II). Like compound (I), it crystallizes with two independent molecules in the asymmetric unit. The two molecules differ essentially in the orientation of the hydrazinecarbothioamide unit with respect to the central benzene ring. This dihedral angle is 5.95 (8) in the first molecule and 42.56 (9) in the second. The benzoate groups are relatively planar and are inclined to the central benzene ring by 72.23 (7) and 53.10 (9) , respectively, in the first and second molecules. Hence, the conformation of the second molecule resembles that of compound (II).

Synthesis and crystallization
Compounds (I) and (II): Thiosemicarbazide (0.91g, 0.01 mol) was added to 50 ml of an ethanolic solution of the 4-acetyl phenyl acetate (0.01 mol) for (I), and to an ethanolic solution of the 4-acetylphenyl benzoate (0.01 mol) for (II), with continuous stirring for 4-5 h. The resulting mixtures were refluxed at 333 K and the purity of the products as well as composition of the reaction mixtures was monitored by TLC using ethyl acetate: hexane (3:7). The reaction mixtures were cooled to room temperature and the separated products were filtered, dried and finally recrystallized from chloroform, solution, yielding block-like yellow crystals of (I) and paleyellow crystals of (II).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. Hydrogen atoms were placed in calculated positions and refined as riding atoms: C-H = 0.93-0.96 Å and N-H = 0.86 Å , with U iso (H) = 1.5U eq (C-methyl) and 1.2U eq (C,N) for other H atoms.   Table 1) and H atoms not involved in hydrogen bonds have been excluded for clarity.

(I) (E)-4-[1-(2-Carbamothioylhydrazinylidene)ethyl]phenyl acetate
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )      (Sheldrick, 2015), Fc * =kFc[1+0.001xFc 2 λ 3 /sin(2θ)] -1/4 Extinction coefficient: 0.080 (6) 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.