Three 4-(4-fluorophenyl)piperazin-1-ium salts containing organic anions: supramolecular assembly in one, two and three dimensions

Three salts containing the 4-(4-fluorophenyl)piperazin-1-ium cation have been prepared and structurally characterized.


Structural commentary
Compounds (I)-(III) are all 1:1 salts  in which a single proton has been transferred from the diprotic acid component to the 4-(4-fluorophenyl)piperazine component: of these, (I) and (II) both crystallize in solvent-free form, but (III) crystallizes as a monohydrate. Since a single enantiomer of tartaric acid, the (2R,3R) form, was used in the synthesis of (III), which occurred under very mild conditions unlikely to induce any stereochemical changes, only a single enantiomer is present in the product, which therefore crystallizes in a Sohncke space group containing neither inversion nor reflection (mirror or glide) operations, here P2 1 2 1 2 1 .
In the anions in each of compounds (I)-(III), the location of the remaining acidic H atom was initially deduced from difference-Fourier maps, and then confirmed by refinement of the atomic coordinates, reinforced by inspection of the final difference-Fourier map and of the relevant C-O bond lengths, where the single and double bonds have distances entirely typical of their types (Allen et al., 1987).
In the anion of compound (I) (Fig. 1), it is the phenolic proton that has been transferred rather than the carboxyl proton; this was confirmed as described above. The other bond lengths in this anion show some interesting features. Firstly, the distance C32-O33, 1.2719 (18) Å , is much closer to the values typically found in cyclohexanones (mean value, 1.211 Å ) than to those found in phenols (mean value 1.362 Å ); secondly, the bond lengths C31-C32 and C32-C33, 1.441 (2) and 1.4318 (19) Å , respectively, are much longer than the other C-C distances in this ring, which lie in the range from 1.368 (2) to 1.388 (2) Å . The bond lengths in the anion, taken together, thus indicate extensive delocalization of the negative charge away from atom O33 and onto the aromatic ring atoms C31,C33,C34,C35,C36 (cf. Scheme), as has been observed in picrate (2,4,6-trinitrophenolate) anions (Sagar et al., 2017;Shaibah et al., 2017a,b). However, this anion is not completely planar: the substituents at atoms C31, C33 and C35 make The independent components of compound (II) showing the atomlabelling scheme and the hydrogen bonds (drawn as dashed lines) within the asymmetric unit. Displacement ellipsoids are drawn at the 30% probability level.

Figure 3
The independent components of compound (III) showing the atomlabelling scheme and the hydrogen bonds (drawn as dashed lines) within the asymmetric unit. Displacement ellipsoids are drawn at the 30% probability level.

Figure 1
The independent components of compound (I) showing the atomlabelling scheme and the hydrogen bonds (drawn as dashed lines) within the asymmetric unit. Displacement ellipsoids are drawn at the 30% probability level. dihedral angles with the plane of the ring of 7.62 (16), 9.31 (12), and 10.9 (2) , respectively.
By contrast, the anion in compound (II) (Fig. 2) is planar: the r.m.s. deviation from the mean plane through the non-H atoms is only 0.014 Å , with a maximum individual deviation from this plane of 0.0186 (6) Å for atom O34. In the anion of (III), the carboxyl and carboxylate groups are antiperiplanar, as shown by the value of À178.81 (10) for the torsional angle C31-C32-C33-C34, while the disposition of the two hydroxyl groups is indicated by the value of À66.5 (3) for the torsional angle O33-C32-C33-O34. Together with the torsional angles O31-C32-C33-C34 and O36-C34-C33-C32, 64.7 (4) and 59.5 (3) , respectively, the torsional angles overall indicate that the non-H atoms in this anion exhibit approximate, although non-crystallographic, two-fold rotation symmetry.

Figure 4
Part of the crystal structure of compound (I) showing the formation of a hydrogen-bonded chain of rings running parallel to [001]. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the H atoms bonded to C atoms have been omitted.

Figure 5
Part of the crystal structure of compound (II) showing the formation of a hydrogen-bonded chain of rings running parallel to the [010] direction. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the H atoms bonded to C atoms have been omitted.
The component ions in compound (II) (Fig. 2) are linked by a single N-HÁ Á ÁO hydrogen bond ( Table 2). The ion pairs, which are related by a 2 1 screw axis along (0.5, y, 0.25), are linked by a combination of an asymmetric three-centre N-HÁ Á Á(O) 2 hydrogen bond and a two-centre O-HÁ Á ÁO hydrogen bond (Table 2) to form a complex chain of rings running parallel to the [010] direction (Fig. 5). This chain is reinforced by two C-HÁ Á ÁO hydrogen bonds, involving methylene atoms C2 and C6 as the donors. However, the combination of the C-HÁ Á ÁO hydrogen bond having methylene atom C5 as the donor and the C-HÁ Á Á(arene) hydrogen bond having atom C2 as the donor links ion pairs, which are related by the c glide plane at y = 0.75, to form a second chain of rings, this time running parallel to the [001] direction (Fig. 6). The combination of chains along [010] and [001] generates a complex sheet lying parallel to (100). There is a fairly short OÁ Á ÁC contact between inversion-related anions, with a distance O31Á Á ÁC32 i [symmetry code: (i) 1 À x, 1 À y, 2 À z] of 3.0108 (14) Å , but it is unclear whether this has any structural significance.
The supramolecular assembly in the monohydrate (III) is more complex than that in either (I) or (II), and it is threedimensional as opposed to the one-and two-dimensional assembly in (I) and (II), respectively. However, the threedimensional assembly in (III) can readily be analysed in terms of some simpler sub-structures (Ferguson et al., 1998a,b;Gregson et al., 2000). Within the asymmetric unit (Fig. 3), the components are linked by two N-HÁ Á ÁO hydrogen bonds and one O-HÁ Á ÁO hydrogen bond (Table 3), forming a compact aggregate containing an R 3 3 (11) motif (Fig. 3). The interaggregate hydrogen bonds having atoms O36 and O41 as the donors link aggregates related by translation to form a sheet lying parallel to (001) in the domain 0.5 < z < 1.0 (Fig. 7). Part of the crystal structure of compound (II) showing the formation of a chain of rings running parallel to the [001] direction and built from C-HÁ Á ÁO and C-HÁ Á Á(arene) hydrogen bonds. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the H atoms bonded to the C atoms not involved in the motif shown have been omitted. Table 3 Hydrogen-bond geometry (Å , ) for (III).

Figure 7
Part of the crystal structure of compound (III) showing the formation of a hydrogen-bonded sheet lying parallel to (001). Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the H atoms bonded to C atoms have been omitted. axes parallel to [100], lies in the domain 0 < z < 0.5 and adjacent sheets of this type are linked into a bilayer by a combination of N-HÁ Á ÁO and O-HÁ Á ÁO hydrogen bonds (Table 3). Finally, the bilayers are linked into a continuous three-dimensional structure by a single C-HÁ Á Á(arene) hydrogen bond: in combination with the N-HÁ Á ÁO hydrogen bond linking the ion pairs within the asymmetric unit, this C-HÁ Á Á interaction generates a chain running parallel to the [001] direction ( Fig. 8), thereby linking adjacent bilayers.

Related structures
It is of interest briefly to compare the structures reported here with those of some closely related compounds. An obvious comparison is between compound (I), reported here and the analogous salt (IV) derived from MeOPP (Kiran Kumar et al., 2019). Although (I) and (IV) both crystallize in space-group type P2 1 /c, their unit-cell dimensions are very different, as is the manner of their supramolecular assembly. Thus, in the structure of (IV), a combination of N-HÁ Á ÁO and C-HÁ Á ÁO hydrogen bonds links the component ions into a chain of centrosymmetric rings in which rings of R 2 2 (10) and R 4 6 (16) types alternate, with chains of this type linked by C-HÁ Á Á(arene) hydrogen bonds to form a three-dimensional network, as compared with the one-dimensional assembly in (I). Thus a change in one small passive substituent between compounds (I) and (IV) is associated with a considerable change in the crystal structure. The constitution of compound (II) has some resemblance to the hydrogensuccinate (V) and hydrogenfumarate (VI) salts of MeOPP, in both of which anions exhibits some disorder (Kiran Kumar et al., 2019). In each of (V) and (VI) the component ions are linked by a combination of O-HÁ Á ÁO and N-HÁ Á ÁO hydrogen bonds to form sheets, which are in turn linked into a three-dimensional assembly by C-HÁ Á Á(arene) hydrogen bonds, as compared to the two dimensional assembly in (II). We also note that structures have been reported for 4-[bis(4-fluorophenyl)methyl)piperazine (VII) (Dayananda et al., 2012a), and for its 1-acetyl derivative (VIII) (Dayananda et al., 2012b), both of which are intermediates on the synthetic pathway to the calcium-channel blocker flunarizine, 1-[bis(4-fluorophenyl)methyl]-4-cinnamyl-piperazine (IX) (Prasanna & Row, 2001).

Synthesis and crystallization
All starting materials were obtained commercially, and all were used as received. For the preparation of compounds (I)-(III), N-(4-fluorophenyl)piperazine (100 mg, 0.55 mmol) was dissolved in methanol (10 ml) and a solution of the appropriate acid (0.55 mmol) in methanol (10 ml) [2-hydroxy-3,5dinitrobenzoic acid, 125.5 mg for (I), oxalic acid, 49.5 mg for (II), and (2R,3R)-tartaric acid, 82.5 mg for (III)] was then added; the mixtures were briefly stirred at 323 K before being set aside at ambient temperature to crystallize. After two days, the resulting solid products were collected by filtration and dried in air. Crystals suitable for single-crystal X-ray diffraction were grown by slow evaporation, at ambient temperature and in the presence of air, of solutions in ethyl acetate for (I) and (III), or in methanol for (II): m.p. (I) 460-463 K, (II) 421-425 K, (III) 437-441 K.

Refinement
Crystal data, data collection and refinement details are summarized in Table 4. All H atoms were located in difference-Fourier maps. The H atoms bonded to C atoms were then treated as riding atoms in geometrically idealized positions with C-H distances 0.93 Å (aromatic), 0.97 Å (CH 2 ), or 0.98 Å (aliphatic C-H) and with U iso (H) = 1.2U eq (C). The H atoms bonded to N or O atoms were refined with U iso (H) = 1.2U eq (N) or 1.5U eq (O), giving the N-H and O-H distances shown in Tables 1-3. In the absence of significant resonant scattering in compound (III), the Flack x parameter (Flack, 1983) was indeterminate (Flack & Bernardinelli, 2000): thus the value of x, calculated (Parsons et al., 2013) using 683 quotients of type [(I + ) À (I À )]/[(I + ) + (I À )], was À1.5 (7). Since a single enantiomer, the (2R,3R) form, of tartaric acid was used in the preparation of compound (III), the absolute configuration in the crystal of (III) was set on this basis.

Acknowledgements
CHC thanks University of Mysore for research facilities.