Crystal structures of 2,3-bis(4-chlorophenyl)-1,3-thiazolidin-4-one and trans-2,3-bis(4-chlorophenyl)-1,3-thiazolidin-4-one 1-oxide

In the related title compounds, (1) and (2), the 3-thiazolidine ring pucker is twisted on the S—Cmethine bond in (1), while in (2), the ring has an envelope conformation with the S atom as the flap. In the crystal of (1), molecules are linked by C—H⋯O hydrogen bonds forming chains along [100], while in the crystal of (2), molecules are linked by C—H⋯O and C—H⋯Cl hydrogen bonds forming slabs parallel to (001).


Chemical context
1,3-Thiazolidin-4-ones, also known as 4-thiazolidinones, are known to have a wide range of biological activities (Jain et al., 2012;Abhinit et al., 2009;Hamama et al., 2008;Singh et al., 1981;Brown, 1961;Tripathi et al., 2014;Prabhakar et al., 2006). The S-oxides have been observed to show enhanced activity, for example, it was shown that on converting a 4-thiazolidinone to its sulfoxide and sulfone, the oxide showed greater activity against some cancer cell lines than the sulfide (Gududuru et al., 2004). Oxidation from sulfide to sulfoxide makes the sulfur a chiral center, and produces cis and trans diastereomers with regard to the relationship of the oxygen atom attached to the S atom and the substituent at the 2position (Rozwadowska et al., 2002;Colombo et al., 2008). The stereocenters may however be configurationally unstable in solution or even in the solid state (Rozwadowska et al., 2002). We have previously reported on the preparation and NMR studies of a series of 2,3-diaryl-1,3-thiazolidin-4-ones in which the two aryl groups had the same substitution pattern (Tierney et al., 2005). In this study, we report on the S-oxidation of one of these compounds, 2,3-bis(4-chlorophenyl)-1, 3-thiazolidin-4-one (1), with Oxone (Trost & Curran, 1981;Yu et al., 2012;Webb, 1994), which gave compound (2), and on their crystal structures. ISSN 2056-9890

Structural commentary
The molecular structures of compounds (1) and (2), Figs. 1 and 2, respectively, show a slight dissimilarity in the thiazine ring conformation. In (1), the ring pucker is twisted on the S1-C1 bond, while in (2) the ring has an envelope conformation with atom S1 as the flap. The structures also differ in the disposition of the chlorophenyl ring at atom C1. In (1), this ring points in the same direction as the S atom with respect to the thiazolidine ring plane, while in (2), the S atom points in the opposite direction. The trans relationship between the oxygen atom on the S atom and the aromatic ring on C1 is favoured due to steric hindrance which would occur in the cis isomer. The chlorophenyl rings are almost orthogonal to each other, making a dihedral angle of 78.61 (6) in (1) and 87.46 (8) in (2).
Comparison of the two structures shows that the oxygensulfur bond in (2) formed on the less hindered side of compound (1), away from the aryl group on C1, leading to a trans stereoisomer. Steric strain was further relieved by twisting so that both the aryl ring on C1 and the oxygen on S1 became pseudo-axial.

Supramolecular features
In the crystal of (1), molecules are linked via C-HÁ Á ÁO hydrogen bonds, forming chains along [100]; see Table 1 and Fig. 3. The chains are linked via slipped parallelinteractions involving inversion-related chlorophenyl rings, leading to the formation of sheets parallel to (001)  A view of the molecular structure of compound (1), with atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Figure 2
A view of the molecular structure of compound (2), with atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Synthesis and crystallization
Compound (1): prepared as previously reported (Tierney et al., 2005). Colourless block-like crystals were obtained by slow evaporation of a solution in ethanol. Compound (2): 2,3-bis (4-chlorophenyl)-1,3-thiazolidin-4-one (1) (0.326 g, 1 mmol) was added to a 25 ml round-bottom flask. Methanol (4 ml) was added and the mixture was stirred at room temperature before cooling to 273-278 K. A solution of Oxone (0.456 g, 3.0 mmol calculated as KHSO 5 , 152.2 g mol À1 ) in distilled water (4 ml) was prepared. This solution (2.67 ml, 2 equivalents) was slowly added to the reaction mixture with stirring at 273-278 K. The reaction was followed by TLC. An additional aliquot of Oxone solution (0.67 ml) was added to convert the remaining starting material to sulfoxide. The mixture was extracted three times with methylene chloride. The organic layers were combined and washed with water and saturated NaCl, then dried over sodium sulfate. The solution was concentrated under vacuum to give compound (2) as a crude solid. The solid was recrystallized from a mixture of methylene chloride and hexane, and then dried (yield: 0.2413 g; 70.5%; m.p.: 406-409 K). Colourless plate-like crystals were obtained by slow evaporation of a solution in ethanol.

Figure 4
Crystal packing of compound (2) viewed along the b axis, showing the hydrogen bonds as dashed lines (see Table 2 for details; H atoms not involved in these interactions have been omitted for clarity). Green Chem. 14, 957-962.  Table 3 Experimental details.

Special details
Experimental. The data collection nominally covered a full sphere of reciprocal space by a combination of 4 sets of ω scans each set at different φ and/or 2θ angles and each scan (10 s exposure) covering -0.300° degrees in ω. The crystal to detector distance was 5.82 cm. 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. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.