Crystal structures of six 4-(4-nitrophenyl)piperazin-1-ium salts

Six piperazinium salts are reported, five of them are hydrated and two crystallized as 2:2 salts. They exhibit asymmetric units of a common 4-nitrophenylpiperazine cation and different p-substituent benzoate anions. Their crystal structures mainly pack as chains stabilized by strong N—H⋯O and O—H⋯O hydrogen bonds and other weak interactions such as C—H⋯O and C—H⋯π.

ÁC 7 H 4 BrO 2 À Á2H 2 O, (I), 4-(4-nitrophenyl)piperazin-1-ium 4-iodobenzoate dihydrate, C 10  , (VI), have been synthesized and their crystal structures solved by single-crystal X-ray diffraction, revealing that all of them crystallize in the triclinic space group P1 except for (V), which crystallizes in the monoclinic space group P2 1 /c and has a disordered nitro group. Compounds (I) and (II) are isostructural. The crystal packing of (I)-(V) is constructed from organic chains formed by a combination of hydrogen bonds of type N-HÁ Á ÁO and/or O-HÁ Á ÁO and other weak interactions of type C-HÁ Á ÁO and/or C-HÁ Á Á, forming sheets, whereas (VI) shows a cationic and anionic-based layer structure.

Chemical context
Piperazines and substituted piperazines are important pharmacophores that can be found in many biologically active compounds used to treat a number of different diseases (Berkheij, 2005) as antifungal (Upadhayaya et al., 2004), antibacterial, anti-malarial and anti-psychotic agents (Choudhary et al., 2006). A valuable insight into advances on the antimicrobial activity of piperazine derivatives was given by Kharb et al. (2012). Piperazines are among the most important building blocks in current drug discovery and are found in biologically active compounds across a number of different therapeutic areas (Brockunier et al., 2004;Bogatcheva et al., 2006). Pharmacological and toxicological information for piperazine derivatives is reviewed by Elliott (2011).

Figure 2
The independent components of compound (II) showing the atomlabelling scheme and the hydrogen bonds, drawn as dashed lines. Displacement ellipsoids are drawn at the 50% probability level.

Figure 4
The independent components of compound (IV) showing the atomlabelling scheme and the hydrogen bonds, drawn as dashed lines. Displacement ellipsoids are drawn at the 50% probability level.

Figure 5
The independent components of compound (V) showing the atomlabelling scheme and the hydrogen bonds, drawn as dashed lines. Displacement ellipsoids are drawn at the 50% probability level.

Figure 6
The independent components of compound (VI) showing the atomlabelling scheme Displacement ellipsoids are drawn at the 50% probability level.

Figure 11
(a) A general view of the main intermolecular interactions (N-HÁ Á ÁO and O-HÁ Á ÁO) in (V) and (b) the molecular packing of (V) with hydrogen bonds shown as dashed lines.  Groom et al., 2016) for the phenyl piperazinium cation and para substituent benzoate anion involved in the reported six salts gave the following hits, 4-(4-methoxyphenyl)piperazin-1-ium 4-fluorobenzoate monohydrate, 4-(4-methoxyphenyl)piperazin-1-ium 4-chlorobenzoate monohydrate and 4-(4-methoxyphenyl)piperazin-1ium 4-bromobenzoate monohydrate (FOVPOY, FOVPUE and FOVQAL;Kiran Kumar et al., 2019) and 4-(4-methoxyphenyl)piperazin-1-ium 4-iodobenzoate monohydrate (KUJ-PUD; Kiran Kumar et al., 2020). They exhibit a methoxy group as a substituent in the phenyl piperazinium cation rather than a nitro group as in the title compounds (I)-(VI) and they also crystallize as monohydrates similar to compounds (III)-(V). Although the title compounds (I) and (II) have halogen-based anions and chain-based structures, they are not isostructural with the above compounds, the crystal structures of which are based on differently sized chains of rings formed via a combination of hydrogen bonds of type N-HÁ Á ÁO and O-HÁ Á ÁO and other weak interactions of type C-HÁ Á ÁO and C-HÁ Á Á to form sheets. In 4-(4-methoxyphenyl)piperazin-1-ium 4-aminobenzoate monohydrate (IHIMEU; Kiran Kumar et al., 2020) the presence of an amino substituent on the anion, which acts as both a donor and an acceptor of hydrogen bonds, makes the supramolecular assembly of this compound more complex than for the compounds reported herein.

Refinement
Crystal data, data collection and refinement details are summarized in Table 7. C-bound H atoms were positioned with idealized geometry and refined using a riding model with C-H = 0.93 Å (aromatic), 0.96 Å (methyl) or 0.97 Å (methylene). The H atoms on the N atom were located in a difference map and later restrained to N-H = 0.86 (2) Å . All H atoms were refined with isotropic displacement parameters set at 1.2 U eq (C-aromatic, C-methylene, N) or 1.5 U eq (Cmethyl) times those of the parent atom. For the disordered nitro group in (V), the component atoms were restrained to have the same U ij components and the occupancy ratio is 0.519 (6):0.481 (6).

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 on F 2 Least-squares matrix: full R[F 2 > 2σ(F 2 )] = 0.029 wR(F 2 ) = 0.069 S = 1.03 3513 reflections 262 parameters 6 restraints 0 constraints Hydrogen site location: mixed H atoms treated by a mixture of independent and constrained refinement w = 1/[σ 2 (F o 2 ) + (0.0319P) 2 + 0.5892P] where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.54 e Å −3 Δρ min = −0.66 e Å −3 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.

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.

4-(4-Nitrophenyl)piperazin-1-ium 4-methylbenzoate monohydrate (IV)
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.

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 )
x y z U iso */U eq Occ. (   where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.23 e Å −3 Δρ min = −0.22 e Å −3 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.