Crystal structure of ebastinium 3,5-dinitrobenzoate

In the cation of the title molecular salt, one of the non-H substituents on the piperidine ring occupies an equatorial site and the other an axial site. The ions are linked into sheets by a combination of one N—H⋯O and two C—H⋯O hydrogen bonds.

are linked within the selected asymmetric unit a by a fairly short and nearly linear N-HÁ Á ÁO hydrogen bond (Fig. 1, Table 1). The disubstituted aryl ring in the cation is disordered over two sets of atomic sites having occupancies 0.706 (4) for the major ring orientation, labelled C161-C166, and 0.294 (4) for the minor orientation, labeled C171-C176: the dihedral angle between these two ring planes is 41.2 (5) (Fig. 1). The piperidine ring adopts an almost perfect chair conformation, with a ring-puckering angle, calculated for the atom sequence (N1,C2,C3,C4,C5,C6) of = 0.0 (3) , identical within experimental uncertainty to the idealized value for a perfect chair form of = 0.0 (Boeyens, 1978). However, although the non-H substituent at atom N1 in the ring occupies an equatorial site, as expected, the bulky Ph 2 CHO substituent at atom C4 unexpectedly occupies an axial site. This observation is the more surprising since in ebastine itself, both non-H substituents on the piperidine ring occupy equatorial sites (Cheng et al., 2005: Sharma et al., 2015. The 3,5-dinitrobenzoate anion in compound (I) is nearly planar: the dihedral angles between the aryl ring and the substituents at atoms C21, C23 and C25 are 1.4 (2), 4.2 (2) and 10.7 (2) , respectively: only the O atoms of the 5-nitro group are significantly displaced from the mean plane of the anion as a whole, 0.219 (2) Å for atom O25 and 0.187 (2) Å for atom O26: the r.m.s. deviation from the mean plane for the entire anion is only 0.082 Å .

Supramolecular features
In addition to the N-HÁ Á ÁO hydrogen bond within the selected asymmetric unit, already noted (cf. Fig. 1 and Table 1), there are two C-HÁ Á ÁO hydrogen bonds in the crystal of compound (I), which link the components into complex sheets, whose formation can, however, be readily analysed in terms of two simple, one-dimensional sub-structures (Ferguson et al., 1998a,b;Gregson et al., 2000). In the simpler of the two substructures, cations related by translation are linked by a single C-HÁ Á ÁO hydrogen bond to form a C(6) chain running parallel to the [100] direction (Fig. 2, Table 1). The second substructure involves the cations and the anions, and a combination of the N-HÁ Á ÁO hydrogen bond and a second C-HÁ Á ÁO hydrogen bond links ions related by a c-glide plane into a C 2 2 (11) chain, running parallel to the [201] direction, in which cations and anions alternate (Fig. 3, Table 1). The combination of these two chain motifs generates a sheet lying parallel to (010) in the domain 0.5 < y < 1.0, and a second such sheet, related to the first by inversion, lies in the domain 0.0 < y < 0.5, but there are no direction-specific interactions between adjacent sheets. It is interesting to note that none of the hydrogen The molecular structure of the ionic components of compound (I), showing the atom-labelling scheme, the N-HÁ Á ÁO hydrogen bond within the selected asymmetric unit, and the orientational disorder of the disubstituted aryl ring (the major component is drawn with full lines and the minor component with broken lines). Displacement ellipsoids are drawn at the 30% probability level and, for clarity, a few of the atom labels have been omitted. Table 1 Hydrogen-bond geometry (Å , ). Symmetry codes: (i) x À 1; Ày þ 3 2 ; z þ 1 2 ; (ii) x À 1; y; z.

Figure 2
Part of the crystal structure of compound (I), showing a hydrogenbonded C(6) chain of cations running parallel to [100]. For clarity, the anions, the minor disorder component of the cation, and the H atoms bonded to carrier atoms not involved in the motif shown have been omitted. The atoms marked with an asterisk (*) or a hash (#) are at the symmetry positions (À1 + x, y, z) and (1 + x, y, z) respectively. bonds in compound (I) involves the Ph 2 CHO substituent, so that direction-specific interactions cannot be held responsible for the location of this substituent at an axial site on the piperidine ring.

Database survey
The molecular structure of neutral ebastine (Cheng et al., 2005;Sharma et al., 2015) differs from that of the ebastinium cation in compound (I) in two significant respects. Firstly, there is no disorder in the neutral compound as opposed to the orientation disorder of the disubstituted aryl ring in (I) and secondly, both of the non-H substituents on the piperidine ring occupy equatorial sites in the neutral compound as opposed to the presence of one axial and one equatorial substituent in (I).
Neither of the two reports on the structure of ebastine gave any description of the supramolecular assembly: one (Cheng et al., 2005) noted the presence of hydrogen bonds, but the second (Sharma et al., 2015) did not record these. Accordingly, we have now examined the supramolecular assembly of ebastine using the most recently reported atomic coordinates (Sharma et al., 2015): a combination of one C-HÁ Á ÁN hydrogen bond and one C-HÁ Á ÁO hydrogen bond links the molecules into sheets lying parallel to (100) and containing R 2 2 (20) and R 6 6 (48) rings, both centrosymmetric, arranges in chess board fashion (Fig. 4). Structures have also been reported recently for some structurally related compounds with pharmacological activity, including the picrate salt of the anticholinergic drug propiverine, 4-(2,2-diphenyl-2-propoxyacetoxy)-1-methylpiperidin-1-ium picrate (Jasinski et al.,

Synthesis and crystallization
A sample of ebastine was a gift from RL Fine Chem, Pvt. Ltd., Bengaluru, India. For the synthesis of compound (I), ebastine (100 mg, 0.20 mmol) and 3,5-dinitrobenzoic acid (45 mg, 0.20 mmol) were dissolved in hot methanol and held at 333 K for 30 min, with magnetic stirring throughout. The resulting solution was then allowed to cool slowly to room temperature, giving colourless block-like crystals (m.p. 424-428 K).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. Three low-angle reflections (021), (002) and (012), which had been attenuated by the beam stop, were omitted from the refinements. It was apparent from an early stage in the refinement that the disubstituted aryl ring was disordered over two sets of atomic sights having unequal occupancies, and corresponding to different orientations of Part of the crystal structure of ebastine showing the formation of a hydrogen-bonded sheet of R 2 2 (20) and R 6 6 (48) rings. The original atomic coordinates (Sharma et al., 2015) have been used and, for the sake of clarity, the H atoms not involved in the motifs shown have been omitted.

Figure 3
Part of the crystal structure of compound (I), showing a hydrogenbonded C 2 this ring relative to its substituents. For the minor orientation, the bonded distances and the 1,3-non-bonded distances were restrained to be the same as the corresponding distances in the major orientation, subject to s.u.s of 0.01 and 0.02 Å , respectively: in addition, the anisotropic displacement parameters for corresponding pairs of atomic sites were constrained to be equal. All H atoms, other than those in the minor disorder components, were located in difference-Fourier maps. The C-bound H atoms were all treated as riding atoms in geometrically idealized positions: C-H 0.93 Å (aromatic), 0.96 Å (CH 3 ), 0.97 Å (CH 2 ) or 0.98 Å (aliphatic C-H), with U iso (H) = 1.5U eq (C-methyl) and 1.2U eq (C) for other H atoms. The methyl groups were permitted to rotate but not to tilt. For the H atom bonded to the N atom, the atomic coordinates were refined with U iso (H) = 1.2U eq (N), giving an N-H distance of 0.99 (3) Å . Subject to these conditions, the occupancies of the two disordered components refined to 0.706 (4) (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015) and PLATON (Spek, 2009).

4-(Benzhydryloxy)-1-[4-(4-tert-butylphenyl)-4-oxobutyl]piperidinium 3,5-dinitrobenzoate
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.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )