Crystal structures of two 1,3-thiazolidin-4-one derivatives featuring sulfide and sulfone functional groups

The closely related title compounds are comprised of three types of rings: thiazolidinone, nitrophenyl and cyclohexyl. In both structures, the rings are close to mutually perpendicular, with interplanar dihedral angles greater than 80° in each case.

The crystal structures of two closely related compounds, 1-cyclohexyl-2-(2nitrophenyl)-1,3-thiazolidin-4-one, C 15 H 18 N 2 O 3 S, (1) and 1-cyclohexyl-2-(2nitrophenyl)-1,3-thiazolidin-4-one 1,1-dioxide, C 15 H 18 N 2 O 5 S, (2), are presented. These compounds are comprised of three types of rings: thiazolidinone, nitrophenyl and cyclohexyl. In both structures, the rings are close to mutually perpendicular, with interplanar dihedral angles greater than 80 in each case. The thiazolidinone rings in both structures exhibit envelope puckering with the S atom as flap and the cyclohexyl rings are in their expected chair conformations. The two structures superpose fairly well, except for the orientation of the nitro groups with respect to their host phenyl ring, with a difference of about 10 between 1 and 2. The extended structure of 1 has two kinds of weak C-HÁ Á ÁO interactions, giving rise to a closed ring formation involving three symmetryrelated molecules. Structure 2 has four C-HÁ Á ÁO interactions, two of which are exclusively between symmetry-related thiazolidinone dioxide moieties and have a parallel 'give-and-take-fashion' counterpart. In the other two interactions, the nitrophenyl ring and the cyclohexane ring each offer an H atom to the two O atoms on the sulfone group. Additionally, a C-HÁ Á Á interaction between a C-H group of the cyclohexane ring and the nitrophenyl ring of an adjacent molecule helps to consolidate the structure.

Chemical context
The title compounds were synthesized as a part of our ongoing work on the synthesis of new types of 2,3-disubstituted 1,3thiazolidin-4-ones. We have reported the crystal structures of a number of these compounds before (Nuriye et al., 2018;Yennawar et al., 2015). These compounds are synthesized by a tandem nucleophilic addition-carbonyl condensation of thioglycolic acid with the desired in situ-generated imine. The variation in substitution pattern is set during the synthesis of the imine where alkyl or aryl amines are condensed with an aldehyde (Surrey, 1947;von Erlenmeyer & Oberlin, 1947). In addition, the S atom in the thiazolidinone ring can be oxidized to the sulfoxide or the sulfone to produce structures with different properties. Thiazolidinones have well documented biological activity (Thakare et al., 2018;Brown, 1961;Abdel Rahman et al., 1990;Joshi et al., 2014;Suryawanshi et al., 2017;Kaushal & Kaur, 2016;Kumar et al., 2015;Tripathi et al., 2014;Jain et al., 2012;Abhinit et al. 2009;Hamama et al., 2008;Singh et al., 1981). The synthesis and characterization of these ISSN 2056-9890 compounds could be valuable in investigations for the practical applications of their activities. To the best of our knowledge, only two crystal structures of thiazolidinone sulfones have been reported in the literature (Orsini et al., 1995;Glasl et al., 1997). The compounds presented in this paper both feature an ortho-nitrophenyl ring at position 2 and a cyclohexane ring at the 3-position of the thiazolidinone ring. Compound 1 is a sulfide, while compound 2 contains a fully oxidized sulfone functional group.

Structural commentary
Compound 2 is the dioxide version of 1, both comprising of three types of rings, a thiazolidinone (A), a nitrophenyl (B) and a cyclohexyl (C) ring. In each structure, the interplanar dihedral angles between the three pairs of rings are close to orthogonal, with values of (in ascending order) A/C = 84.04 (9), B/C = 84.98 (10) and A/B = 85.85 (9) . The corresponding data for 2 span a slightly wider range: B/C = 80.74 (6), A/B = 83.12 (6) and A/C = 87.96 (6) (Figs. 1 and 2). In both structures, the thiazolidinone rings exhibit an envelope pucker conformation with the sulfur atom as a flap. The cyclohexyl rings are in the most stable chair conformation in both structures. An overlay of the two structures ( Fig. 3) shows that they overlap well. Fig. 3 also shows that the nitro group plane in 2 is twisted further away by ca 10 from the nitrophenyl ring plane as compared to that in 1; the dihedral angles between the nitro group plane and the host phenyl ring plane were found to be 18.3 (5) in 1 and 28.3 (5) in 2. The molecular structure of 2 with displacement ellipsoids drawn at the 50% probability level.

Figure 3
Overlay image of the two title molecules showing the difference in the orientation of the nitro group with respect to the nitrophenyl ring plane.

Figure 1
The molecular structure of 1 with displacement ellipsoids drawn at the 50% probability level.
Looking at the thiazolidinone ring systems, the C1-N1 and C1-S1 bond lengths are 1.438 (3) and 1.839 (3) Å , respectively, for structure 1 and 1.4527 (13) and 1.8382 (12) Å for structure 2. The N-C-S bond angle is found to be 105.22 (12) in structure 1 and 101.36 (7) in structure 2 indicating a compression of the N-C-S bond angle going from the sulfide to the sulfone. Bond length and angle values in the thiazolidinone ring of the sulfide appear to be typical and match data that we have previously reported (Nuriye et al., 2018). Although structural data for the sulfone are scarce, the data reported by Orsini et al. (1995) matches our findings.

Supramolecular features
In structure 1, two weak C-HÁ Á ÁO type interactions (Table 1) result in a closed-ring formation of three symmetry-related molecules (Fig. 4). One of the nitrophenyl-ring carbon atoms donates its H atom to the oxygen atom on the thiazolidinone ring of a neighboring molecule [C8Á Á ÁO1 = 3.411 (5) Å , C-HÁ Á ÁO = 140 ], which then interacts with a third symmetryrelated molecule through a symmetry-equivalent contact. Finally, this third molecule donates one of its cyclohexane protons to the nitrophenyl oxygen atom of the first molecule [C15Á Á ÁO3 = 3.437 (5) Å , 138 ], thus completing the threemolecule ring arrangement. In the extended structure, the molecules arrange themselves in distinct layers in (020) planes. Perpendicular to c, the longest axis, there is an alternating pattern of hydrophobic and hydrophilic surfaces of the molecules, as is evident in the packing diagram (Fig. 5).
In structure 2, we observe four C-HÁ Á ÁO type interactions ( Table 2). Two of these involve the thiazolidinone dioxide moieties exclusively and have parallel 'give-and-take' type counterparts [CÁ Á ÁO = 3.4594 (16) Å , 161 and 3.3068 (16) Å , 157 ], forming continuous chains propagating along the b-axis direction. The remaining two interactions are weaker and involve the carbon atoms of nitrophenyl rings and cyclohexane rings of one molecule offering protons to the oxygen pair of the dioxide group [C9Á Á ÁO1 3.5144 (16) Å , 132.6 and 3.4381 (16) Å , 129 ] of a symmetry-related molecule. Similar to packing of 1, the molecules are arranged in distinct layers but this time in (202) planes. Also seen is the alternating pattern of hydrophobic and hydrophilic surfaces perpendicular to the c-axis direction (Fig. 6). Hydrogen-bond interactions between three symmetry-related molecules of 1 forming a closed-ring system.

Figure 5
View down the a axis of the packing of 1. The layering of molecules in the (020) plane as well as the alternating pattern of hydrophobic and hydrophilic regions perpendicular to c axis can be seen. Table 1 Hydrogen-bond geometry (Å , ) for 1.

Synthesis and crystallization
1-Cyclohexyl-2-(2-nitrophenyl)-1,3-thiazolidin-4-one: Following the reported method (Cannon et al., 2015), 2-nitrobenzaldehyde (0.725 g, 4.80 mmol) was dissolved in CH 2 Cl 2 (20 ml) and anhydrous MgSO 4 (3.0 g) and cyclohexyamine (0.5 g, 5 mmol) were added sequentially and stirred for 4 h at r.t. under nitrogen. The MgSO 4 was filtered off and the reaction was concentrated in vacuo to give 0.9826 g of an orange oil, which solidified upon sitting in a freezer and remained solid upon warming up to room temperature. The crude imine was resuspended in toluene (25 ml) and thioglycolic acid (0.55 g, 6.0 mmol) was added and the reaction was heated at reflux for 1.5 h with a Dean-Stark trap attached. The reaction was then cooled to room temperature and washed with aqueous NaHCO 3 (2 Â 35 ml). The combined organic layers were dried over anhydrous Na 2 SO 4 , filtered, and concentrated under reduced pressure to give an orange oil. The crude substance was purified by flash column chro-matography on silica gel (15 g) using 20-60% ethyl acetate in hexanes as the eluent to yield a yellow solid (0.720 g). The solid was recrystallized from ethanol solution to give a paleyellow solid (0.508 g, 36.4% over two steps Crystals for X-ray data collection were grown by dissolving 0.101 g of the solid in hot ethanol and slow evaporation of the solvent. 1-Cyclohexyl-2-(2-nitrophenyl)-1,3-thiazolidin-4-one 1,1dioxide: 1-Cyclohexyl-2-(2-nitrophenyl)-1,3-thiazolidin-4-one (0.553 mmol) was dissolved in glacial acetic acid (2.4 ml), to which an aqueous solution of KMnO 4 (175 mg, 1.11 mmol, in 3.0 ml water) was added dropwise at room temperature with vigorous stirring, and stirred for an additional 5 min. Solid sodium bisulfite (NaHSO 3 /Na 2 S 2 O 5 ) was then added until the solution remained colorless; 3.0 ml of water was then added and the mixture was stirred for a further 10 min. The resulting solid precipitate was filtered and rinsed with water. The resulting powder was purified by recrystallization from CH 3 OH solution. Yield (64%); m.p. 471-472 K; IR: cm  147.80, 134.43, 131.22, 128.82, 126.92 75.77, 54.52, 50.16, 31.39, 29.67, 25.50, 25.16, 24.84 Crystals for X-ray data collection were grown by slow evaporation of a hot methanol solution of the compound.

Figure 6
View down the b axis of the packing arrangement of 2. The layering of molecules in the (202) plane as well as the alternating pattern of hydrophobic and hydrophilic regions perpendicular to the c axis can be seen.

1-Cyclohexyl-2-(2-nitrophenyl)-1,3-thiazolidin-4-one (1)
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.

1-Cyclohexyl-2-(2-nitrophenyl)-1,3-thiazolidin-4-one 1,1-dioxide (2)
Crystal data where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.45 e Å −3 Δρ min = −0.34 e Å −3 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. 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 > 2sigma(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.