Crystal structure and Hirshfeld surface analysis of two organic salts based on 1,3,4-thiadiazole derivatives

Two organic salts based on 1,3,4 thiadiazole derivatives have been obtained and their structures have been established by single-crystal X-ray analysis.


Chemical context
In the field of medicinal chemistry, the search for new selective drugs with reduced toxicity is ongoing. Heterocyclic compounds with the 1,3,4-thiadiazole structural unit are very attractive for the production of pharmaceuticals as 1,3,4thiadiazole derivatives exhibit a wide spectrum of biological activities. The 1,3,4-thiadiazole moiety acts as a hydrogenbinding dominant unit on the one hand and as an electrondonor unit on the other (Sharma et al., 2013). The sulfur atom of the thiadiazole moiety gives lipophilic properties to these compounds, which provides better permeability through biological membranes (Song et al., 1999). The thiadiazole nucleus with its N-C-S linkage exhibits a large number of biological activities (Kurtzer et al., 1965). It has been found that derivatives of 1,3,4-thiadiazole have diverse pharmacological activities such as fungicidal, insecticidal, bactericidal, herbicidal, anti-tumor (Shivarama Holla et al., 2002), antiinflammatory and antiviral (Witkoaski et al.,1972). A number of 1,3,4-thiadiazoles exhibit antibacterial properties similar to those of well-known sulfonamide drugs. 1,3,4-Thiadiazole derivatives have been patented for agricultural use, as herbicides and bactericides. According to these findings and in a continuation of our work on synthesizing various condensed-bridge bioactive molecules bearing multifunctional and pharmaceutically active groups (Priya et al., 2005;Sadashiva et al., 2004), we have investigated the structural properties of two new 1,3,4-thiadiazole derivatives.

Supramolecular features
In the asymmetric unit of compound (I) there is a protonated 2-amino-5-ethyl-1,3,4-thiadiazole molecule (cation) and half of a doubly deprotonated oxalic acid molecule (anion) (it is on a special position: there is a center of inversion in the middle of the molecule), i.e. the molecular ratio is 2:1. The oxygen atoms of the oxalate anion are involved in intermolecular hydrogen bonding (Table 1) with neighboring cationic species, leading to the formation of one-dimensional infinite chains. Such chains are packed parallel to each other in the [100] direction in the crystal structure (Fig. 3). Each chain consists of alternate eight-and fourteen-membered (including hydrogen atoms) conjugated rings, with the graph-set notations R 2 2 (8) and R 4 4 (14), respectively, according to the hydrogen-bonding patterns defined by Etter et al. (1993). These chains are interconnected via C-HÁ Á ÁO (Table 1, Fig. 4) andinteractions [Cg1Á Á ÁCg1( 1 2 + x, 1 2 À y, 1 2 + z) = 3.7734 (10) Å , where Cg1 is the centroid of the S1/C1/N2/N3/ C2 ring].

Hirshfeld surface calculation
In order to visualize the intermolecular interactions in the structures of compounds (I) and ( Packing diagram of compound (I) viewed down the a-axis. Hydrogen bonds are shown as dashed lines. Table 2 Hydrogen-bond geometry (Å , ) for (II). (5) 3.173 (3) 173 (4)

Figure 5
Packing diagram of compound (II) viewed down the a-axis. The hydrogen bonds are shown as dashed lines.

Figure 3
Packing diagram of compound (I) viewed down the c-axis. Hydrogen bonds are shown as dashed lines.

Synthesis and crystallization
Synthesis of 2-amino-5-ethyl-1,3,4-thiadiazole: Propionic acid (0.108 mol) was mixed with 16 g of sulfuric acid (94%). The reaction temperature was allowed to reach 333-343 K, and then, under the same conditions, 0.1 mol of thiosemicarbazide were added. The mixture was stirred for 3 h at 333-343 K, water and charcoal were added, and the mixture was stirred for 40 minutes. At the end of the reaction, the solution was filtered. Then, 44% sodium hydroxide solution was added to get a solution with pH 9.5-10. After cooling the reaction to 303-308 K, the mixture was filtered. The precipitate was washed with water (303 K) and allowed to dry to give the title compound (12 g, 93%), m.p. 460-467 K. IR (cm À1 ): 3290, 2980, 2780; 1640.
Compound (I) was obtained using the procedure described by Harris et al. (1984). We tried to achieve interaction between 2-amino-5-ethyl-1,3,4-thiadiazole and oxalyl chloride. For this, 20 mmol oxalyl dichloride were mixed with 40 mmol of 2-amino-5-ethyl-1,3,4-thiadiazole in 15 ml of dry acetone, and stirred under boiling acetone for 10 h. The solvent was then removed by rotary evaporation, and the residue was purified by recristallization from water. Beige block-shaped crystals were obtained after one week of slow evaporation of the solvent. We presume that oxalyl chloride was transformed to oxalic acid upon treatment with water in the last step of the reaction.
Compound (II) was obtained during a typical procedure (Sheikh et al., 2010) for the etherification reaction between 5-mercapto-3-phenyl-1,3,4-thiadiazol-2-thione and glutaric anhydride. The isolated reaction products were amorphous. For purification, the reaction products were treated by filtration in ethyl alcohol. Colorless needle-like single crystals were afforded after 2 days by slow evaporation of the solvent.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. In (I), atom H1 (at protonated atom N2 of 2-amino-5-ethyl-1,3,4-thiadiazol-3-ium) was located from difference-Fourier maps. The two-dimensional fingerprint plots for compound (II). The d i and d e values are the closest internal and external distances (in Å ) from a given point on the Hirshfeld surface depicted in Fig. 7.

Figure 8
The two-dimensional fingerprint plots for compound (I). The d i and d e values are the closest internal and external distances (in Å ) from a given point on the Hirshfeld surface depicted in Fig. 6.     (Siemens, 1994), Mercury (Macrae et al., 2020); software used to prepare material for publication: publCIF (Westrip, 2010).

2-Amino-5-ethyl-1,3,4-thiadiazol-3-ium hemioxalate (I)
Crystal data 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.