Crystal structures of two 2,9-dithia-13-azadispiro[4.1.47.35]tetradecan-6-ones

The title compounds, (I) and (II), differ only in the substituent on the N atom of the central piperidine ring; methyl in (I) and benzyl in (II). In each molecule, the 4,11-dihydroxy groups are involved in intramolecular O—H⋯O hydrogen bonds. In the crystal of (I), molecules are linked via O—H⋯N hydrogen bonds, forming chains along the b-axis direction. In the crystal of (II), molecules are linked via O—H⋯O hydrogen bonds, forming inversion dimers with an (8) ring motif.


Chemical context
Piperidine derivatives have had an important impact in the medical field due to their wide variety of pharmacological activities, and they form an essential part of the molecular structure of important drugs (Hema et al., 2005a,b). Piperidine derivatives are used clinically to prevent post-operative vomiting, to speed up gastric emptying before anaesthesia or to facilitate radiological evaluation, and to correct a variety of disturbances of gastro-intestinal functions (Hema et al., 2005a,b). The piperidine structural motif is present in natural alkaloids (Raghuvarman et al., 2014). Notably it is found in the fire ant toxin solenopsin and is an inhibitor of phosphatidylinositol-3-kinase signalling and angiogenesis (Rajalakshmi et al., 2012). Piperidines are known to have CNS depressant action at low dosage levels and stimulant activity with increased doses. They have been used as antitumor (Nguyen Thi Thanh et al., 2014), antimicrobial (Perumal et al., 2014), antifungal, hypoglycaemic, hypolipidemic, anti-acetyl cholinesterase (Singh et al., 2009), anti-coagulant (Mochizuki et al., 2008), antihistamines, anaesthetics, tranquilizers, analgesic, ganglionic blocking and as hypotensive agents (Pandey & Chawla, 2012). The properties of piperidine derivatives depends on the nature of the side groups and their orienta- ISSN 2056-9890 tions. As part of our studies in this area, we have synthesized two new 2,9-dithia-13-azadispiro[4.1.4 7 .3 5 ]tetradecan-6-one derivatives, each incorporating a piperidine ring, and report herein on their crystal structures.

Structural commentary
The molecular structure of compounds, (I) and (II), are shown in Figs. 1 and 2, respectively. A view of the structural overlay of the two compounds is shown in Fig. 3. The essential differences appear to be related to the orientations of the toluyl substituents, viz. rings B an C.
In both molecules there is an intramolecular O-HÁ Á ÁO hydrogen bond present forming an S(6) ring motif. Most piperidine derivatives are known to have chair conformations (Sekar & Parthasarathy et al., 1993). The title compounds are no exception and the piperidine rings (A = C10-C14/N1) adopt distorted chair conformations in both compounds. In The molecular structure of compound (I), showing the atom labelling. Displacement ellipsoids are drawn at the 30% probability level.
In compound (I), the thiophene rings D (C7-C10/S1) and E (C14/C16-C18/S2) have envelope conformations with atoms C10 and C14, respectively, as the flaps. They deviate from the mean plane through the four other atoms in the ring by 0.6277 (15) Å for C10 and 0.6494 (15) Å for C14. The mean plane of the piperidine ring A makes dihedral angles of 75.16 (9) and 73.33 (8) with the mean planes of the thiophene rings D and E, respectively. The mean plane of thiophene ring D makes a dihedral angle of 60.10 (1) with toluyl ring B (C1-C6), and the mean plane of thiophene ring D make a dihedral angle of 58.14 (1) with toluyl ring C (C19-C24). Rings B and C are inclined to one another by 66.39 (13) .
In compound (II), thiophene ring D (C7-C10/S1) has an envelope conformation with atom C9 as the flap. It deviates from the mean plane through the other four atoms by 0.621 (2) Å . Thiophene ring E (C13/C15-C17/S2) has a twisted conformation on the C13-C17 bond. These two atoms deviate from the plane (C15/C16/S2) by 0.291 (2) and À0.490 (2) Å , respectively. The piperidine ring A mean plane makes dihedral angles of 70.95 (11) and 77.43 (12) with the mean planes of thiophene rings D and E, respectively. The mean plane of thiophene ring D make a dihedral angle of 52.42 (1) with toluyl ring B (C1-C6), and the mean plane of thiophene ring D make a dihedral angle of 65.71 (1) with toluyl ring C (C18-C23). Benzyl ring F (C25-C30) makes a dihedral angle of 75.09 (1) with the mean plane of piperidine ring A. Rings B and C are inclined to one another by 74.33 (12) .

Figure 5
A partial view of the crystal packing of compound (I), showing theinteraction (dashed line), involving inversion-related toluyl rings. H atoms not involved in this interaction have been omitted for clarity and the centroids are shown as small red balls.
In the crystal of (II), molecules are linked via O-HÁ Á ÁO hydrogen bonds, forming inversion dimers enclosing an R 4 4 (8) ring motif (Table 2 and Fig. 6). There are C-HÁ Á Á interactions present (Fig. 7) linking the dimers to form slabs parallel to the ab plane.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. The hydroxy H atoms were located in difference Fourier maps. For compound (II), the hydroxy H atom, H3A, was freely refined. Those of compound (I) and the second hydroxy H atom in compound (II) were refined as riding: O-H = 0.82 Å with U iso (H) = 1.5U eq (O). The C-bound hydrogen atoms were placed in calculated positions and refined as riding: C-H = 0.93-0.98 Å with U iso (H) = 1.5U eq (C) for methyl H atoms and 1.2U eq (C) for other H atoms. Table 2 Hydrogen-bond geometry (Å , ) for (II).

Figure 6
The crystal packing of compound (II), viewed along the b axis. Hydrogen bonds are shown as dashed lines (see Table 2 for details). H atoms not involved in hydrogen bonding have been omitted for clarity.

Figure 7
A partial view of the crystal packing of compound (II), showing the C-HÁ Á Á interactions as dashed lines (see Table 2   Computer programs: APEX2 and SAINT (Bruker, 2008), SHELXS97 and SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 2012), Mercury (Macrae et al., 2008) and PLATON (Spek, 2009 For both compounds, data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008). Molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and Mercury (Macrae et al., 2008) for (I); ORTEP-3 for Windows (Farrugia, 2012) for (II). For both compounds, software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009  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.