4-[Bis(4-fluorophenyl)methyl]-1-[(2E)-3-phenylprop-2-en-1-yl]piperazin-1-ium 3-carboxypropanoate

In the title salt, C26H27F2N2 +·C4H5O4 −, the piperazine N atom bearing the vinylic substituent is protonated. The piperazine ring adopts a chair conformation. In ther crystal, the succinate monoanions are connected via short O—H⋯O hydrogen bonds between the carboxylic acid and carboxylate groups into undulating chains extending along [001] and the flunarizinium monocations are attached to these chains via N+—H⋯O− hydrogen bonds. C—H⋯O interactions connect these chains into a three-dimensional network. The shortest centroid–centroid distance of 3.7256 (10) Å was found between one of the fluorinated benzene rings and the non-fluorinated phenyl ring in the neighbouring molecule related by a glide plane.


Experimental
Data collection: APEX2 (Bruker, 2010); cell refinement: SAINT (Bruker, 2010); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: Flunarizine is a drug classified as a calcium channel blocker (Amery, 1983). A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use has been published (Holmes et al., 1984). Piperazines are among the most important building blocks in today's drug discovery and are found in biologically active compounds in a number of different therapeutic areas (Brockunier et al., 2004;Bogatcheva et al., 2006), and a review about the current pharmacological and toxicological information for piperazine derivatives is available (Elliott, 2011). The crystal structures of several related compounds are apparent in the literature (Fillers & Hawkinson, 1982;Vanier & Brisse, 1983;Betz et al., 2011a,b;Dayananda et al., 2012a,b). In continuation of our research about the salts of pharmacologically active compounds the title compound was synthesized and its crystal structure was determined.
Protonation of the flunarizine scaffold occurred on the nitrogen atom bearing the vinylic substituent. According to a puckering analysis (Cremer & Pople, 1975;Boeyens, 1978), the central 1,4-diazacyclohexane ring adopts a 4 C 1 conformation with both nitrogen atoms acting as the flap atoms ( N2 C N1 ). The C=C bond in the vinylic substituent is (E)configured. The least-squares planes defined by the individual carbon atoms of the fluorinated phenyl moieties enclose an angle of 78.09 (8) °. The plane defined by the carbon atoms of the non-halogenated phenyl ring intersects at angles of 11.08 (8) ° and 87.51 (8) ° with the two aforementioned planes. The succinate monoanion is essentially flat (r.m.s. of all fitted non-hydrogen atoms = 0.0955 Å) with one of the carbon atoms of a methylene group deviating most from the common plane by 0.160 (1) Å (Fig. 1). The succinate monoanion adopts a zigzag conformation.
In the crystal, C-H···O contacts whose range falls by up to more than 0.3 Å below the sum of van-der-Waals radii of the atoms participating are observed next to classical hydrogen bonds of the O-H···O and N-H···O type. The C-H···O contacts are supported by both hydrogen atoms of an intracyclic methylene group bonded to the protonated nitrogen atom as well as one hydrogen atom in ortho-position to a fluorine atom in one of the fluorophenyl moieties as donors. The protonated carboxyl group forms a hydrogen bond to the deprotonated carboxyl group, the latter one also serving as acceptor for the N-H···O type hydrogen bonds. In addition, a C-H···π interaction involving one of the hydrogen atoms in meta-position to the fluorine atoms on the fluorophenyl moiety that does not contribute to the C-H···O contacts as described above as the donor and the aromtic system of the non-halogenated phenyl ring as the acceptor is apparent.
Metrical parameters as well as information about the symmetry of these contacts are summarized in Table 1. In total, the entities of the title compound are connected to a three-dimensional network. In terms of graph-set analysis (Etter et al., 1990;Bernstein et al., 1995), the descriptor for these contacts is DC 1 1 (7) for the classical hydrogen bonds on the unary level. The C-H···O contacts necessitate a DDD descriptor on the same level. The shortest intercentroid distance between twomoiety aromatic systems was found at 3.7256 (10) Å and is apparent between one of the fluorinated and the non- The packing of the title compound in the crystal structure is shown in Figure 2.
Experimental Flunarizine (4.05 g, 0.01 mol) and succinic acid (1.18 g, 0.01 mol) were dissolved in hot N,N-dimethylformamide and reacted for 30 minutes. The resulting solution was allowed to cool slowly at room temperature upon which crystals of the title compound appeared in the course of several days. The latter were of sufficient quality for the X-ray diffraction studies.

Refinement
Carbon-bound H atoms were placed in calculated positions (C-H 0.95 Å for aromatic and vinylic carbon atoms, C-H 0.99 Å for methylene groups and C-H 1.00 Å for the methine group) and were included in the refinement in the riding model approximation, with U(H) set to 1.2U eq (C). The H atom of the hydroxyl group was allowed to rotate with a fixed angle around the C-O bond to best fit the experimental electron density [HFIX 147 in the SHELX program suite (Sheldrick, 2008)] with U(H) set to 1.5U eq (O). The nitrogen-bound H atom was located on a difference Fourier map and refined freely.  The molecular structure of the title compound, with atom labels and anisotropic displacement ellipsoids drawn at 50% probability level.