Crystal structure of 2-[(3aS,6R)-3,3,6-trimethyl-3,3a,4,5,6,7-hexahydro-2H-indazol-2-yl]thiazol-4(5H)-one

The absolute structure of the title compound was determined from the synthetic pathway and by resonant scattering. The compound is a new thiazolidin-4-one derivative, prepared from (R)-thiosemicarbazone pulegone, and was isolated on crystallization from ethanol as the pure (3aS,6R)-diastereisomer.

The title compound, C 13 H 19 N 3 OS, is a new thiazolidin-4-one derivative prepared and isolated as the pure (3aS,6R)-diastereisomer from (R)-thiosemicarbazone pulegone. It crystallized with two independent molecules (A and B) in the asymmetric unit. The compound is composed of a hexhydroindazole ring system (viz. a five-membered dihydropyrazole ring fused to a cyclohexyl ring) with a thiazole-4-one ring system attached to one of the pyrazole N atoms (at position 2). The overall geometry of the two molecules differs slightly, with the mean planes of the pyrazole and thiazole rings being inclined to one another by 10.4 (1) in molecule A and 0.9 (1) in molecule B. In the crystal, the A and B molecules are linked via C-HÁ Á ÁO hydrogen bonds, forming slabs parallel to the ab plane. There are C-HÁ Á Á interactions present within the layers, and between the layers, so forming a three-dimensional structure.

Chemical context
Thiazolidinones constitute an important class of heterocyclic compounds containing sulfur and nitrogen in a five-membered ring. They play a vital role due to their wide range of biological activities and industrial importance. Thiazolidin-4-ones are particularly important because of their efficiency towards various pharmacological usages. A recent literature search reveals that thiazolidin-4-one derivatives may exhibit antibacterial (Bonde & Gaikwad, 2004), antituberculosis (Karali et al., 2007), antiviral (Kaushik-Basu et al., 2008) and anticancer activities (Patel et al., 2014).
As a part of our endeavour toward the preparation of new heterocyclic systems, we report herein on the structure of a new optically active thiazolidin-4-one (2) synthesized from (R)-thiosemicarbazone pulegone (1); see Scheme. The reaction involves the treatment of thiosemicarbazone (1), in refluxing ethanol, with ethyl bromoacatete and an excess of sodium acetate. Crystallization from an ethanolic solution of the resulting indazolic thiazolidin-4-one (obtained as a diastereomeric mixture) led to the isolation of compound (2). The structure of (2) was elucidated using spectroscopic (MS and NMR) data, while its absolute structure was determined as (3aS,6R) based mainly on the synthetic pathway and confirmed by resonant scattering.

Structural commentary
The title compound crystallized with two independent molecules (A and B) in the asymmetric unit. The compound is composed of a hexhydroindazole ring system [viz. a fivemembered dihydropyrazole ring fused to a cyclohexyl ring] with a thiazole-4-one ring system attached to pyrazole N atom N2 (Fig. 1). Molecular fitting of the two molecules (Spek, 2009) shows that they have roughly the same conformation and the same configuration ( Fig. 2), even if some slight differences can be observed. The six-membered rings each display a chair conformation, with puckering parameters of = 12.96 and '2 = 113.49 for molecule A and = 9.44 and '2 = 92.43 for molecule B. The five-membered pyrazol rings are almost planar with the largest deviation being 0.081 (3) Å for atom C3 in molecule A and À0.032 (1) for atom C3B in molecule B. The thiazole rings are planar, the largest deviation being À0.011 (1) Å for atom C2 0 and 0.005 (1) for atom C5 0 B in molecules A and B, respectively. In molecule A, the two five-membered rings are slightly twisted with a dihedral angle of 10.4 (1) , whereas in molecule B the two rings are almost coplanar with a dihedral angle of 0.9 (1) .

Supramolecular features
In the crystal, the two independent molecules are connected via C-HÁ Á ÁO hydrogen bonds forming layers, or slabs, parallel to the ab plane (Table 1 and Fig. 3). Within the layers there are C-HÁ Á Á interactions present ( Fig. 4 and Table 1). The layers are also linked by C-HÁ Á Á interactions (Table 1), forming a three-dimensional structure (Fig. 4). View of the molecular structure of the two independent molecules (A and B) of the title compound, showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Figure 3
A view along the a axis of the crystal packing of the title compound, showing the formation of layers parallel to the ab plane via C-HÁ Á ÁO hydrogen bonds (see Table 1). H atoms not involved in these interactions have been omitted for clarity. linked to an N atom of a pyrazole ring, similar to the situation in the title compound, yielded six hits. One of these structures, 2-(3-phenyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazol-2-yl)-1,3thiazol-4(5H)-one (refcode LUHGAY; Gautam & Chaudhary, 2015), resembles the title compound with an indazole ring system linked to a thiazole ring. The mean plane of the two five-membered rings are inclined to one another by ca 10.05 , similar to the arrangement in molecule A of the title compound.

Synthesis and crystallization
The synthesis of the title compound is illustrated in the Scheme. A mixture of thiosemicarbazone (1) (1.5 mmol, 1 eq), ethyl 2-bromoacetate (0.24 ml, 1.5 mmol) and anhydrous sodium acetate (0.37 g, 4.5 mmol, 3 eq) in absolute ethanol (30 ml) was heated under reflux until the completion of the reaction (1-3 h). The solvent was then evaporated under reduced pressure and the crude product was purified by chromatography on silica gel (230-400 mesh) using hexane/ ethyl acetate (90:10) as eluent to give pure indazolic thiazolidin-4-one in 60% yield as a diastereomeric mixture. Slow evaporation from an ethanolic solution gives crystals of the pure diastereoisomer of the title compound (2) suitable for crystallographic analysis.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The C-bound H atoms were included in calculated positions and treated as riding atoms: C-H = 0.96-0.98 Å with U iso (H) = 1.5U eq (C-methyl) and 1.2U eq (C) for other H atoms.

Figure 4
A view along the a axis of the crystal packing of the title compound, showing the C-HÁ Á ÁO hydrogen bonds (dashed lines), and the C-HÁ Á Á interactions (represented by blue arrows) linking the A (black) and B (red) molecules within and between the layers (see Table 1). H atoms not involved in these interactions have been omitted for clarity.