Syntheses and crystal structures of 4-(4-methoxyphenyl)piperazin-1-ium 4-methylbenzoate monohydrate and bis[4-(4-methoxyphenyl)piperazin-1-ium] benzene-1,2-dicarboxylate

Two salts derived from N-(4-methoxyphenyl)piperazine crystallize with six independent molecular species in the asymmetric unit. In each compound, multiple hydrogen bonds link these components into complex sheets.


Chemical context
Piperazine derivatives can exhibit a very wide range of biological activity (Asif, 2015;Brito et al., 2019). In addition, N-(4-methoxyphenyl)piperazine (MeOPP) is a recreational drug whose action on human physiology resembles that of amphetamines, but which appears to have significantly lower potential for abuse (Nagai et al., 2007). With these considerations in mind, we have recently initiated a structural study of MeOPP and its derivatives (Kiran Kiran Kumar, Yathirajan, Sagar et al., 2019;Kiran Kumar et al., 2020): this has included the structures of a number of salts derived from simple aromatic acids (Kiran Kiran Kumar et al., 2020). In a continuation of these earlier studies, we now report the structures of two further salts, namely 4-(4-methoxyphenyl)piperazin-1-ium 4-methylbenzoate monohydrate (I) and bis[4-(4-methoxyphenyl)piperazin-1-ium] benzene-1,2-dicarboxylate (II) (see scheme and Figs. 1-3).

Structural commentary
Co-crystallization of N-(4-methoxyphenyl)piperazine and 4-methylbenzoic acid yielded a 1:1 salt, which crystallized from methanol-ethyl acetate in air as a monohydrate, with Z 0 = 2 in space group P1 (Fig. 1). A search for possible additional symmetry revealed none. The possibility of any such symmetry is effectively precluded by the different orientations of the 4-methoxyphenyl unit relative to the piperazine ring in the two independent cations, as indicated by the values of the torsion angles Cx3-Nx4-Cx41-Cx42 (x = 1 or 2, Fig. 1), À5.45 (18) when x = 1, but À46.92 (17) when x = 2. Apart from this difference, the other pairs of corresponding units (the two piperazine rings, the two anions, and the two water molecules) are related by an approximate, non-crystallographic translation (x, 0.5 + y, z). Although there are six independent components in the structure, it is possible to select a compact asymmetric unit in which the components are linked by three O-HÁ Á ÁO hydrogen bonds and two N-HÁ Á ÁO hydrogen bonds (Fig. 1, Table 1).
Compound (II), formed by co-crystallization of N-(4methoxyphenyl)piperazine with benzene-1,2-dicarboxylic acid (phthalic acid), is a 2:1 salt that crystallizes in solvent-free form with Z 0 = 2 in space group Pna2 1 . A search for possible additional symmetry revealed none. As for compound (I), there are six independent components in the structure of (II), four cations and two anions, providing a considerable degree of choice in the specification of the asymmetric unit. The The six independent components in the structure of compound (I), showing the atom-labelling scheme and the hydrogen bonds, drawn as dashed lines, within the selected asymmetric unit. Displacement ellipsoids are drawn at the 30% probability level.

Figure 2
The independent components in the type 1 ion triplet in compound (II), showing the atom-labelling scheme and the hydrogen bonds, drawn as dashed lines, within the selected triplet. Displacement ellipsoids are drawn at the 30% probability level The independent components in the type 2 ion triplet in compound (II), showing the atom-labelling scheme and the hydrogen bonds, drawn as dashed lines, within the selected triplet. Displacement ellipsoids are drawn at the 30% probability level selection here consists of two similar ion triplets, each comprising two cations and one anion, which are linked in each triplet by two N-HÁ Á ÁO hydrogen bonds (Figs. 2 and 3). It will be convenient to refer to the ion triplet containing atom N11 (Fig. 2) as of type 1, and that containing atom N21 (Fig. 3) as of type 2.
In the cations of compound (I), the methoxy C atoms are close to the plane of the adjacent rings, with displacements from these planes of 0.118 (3) and 0.073 (4) Å for atoms C147 and C247, respectively. In compound (II), the corresponding displacements are 0.242 (6), 0.070 (6) and 0.097 (6) Å for atoms C147, C247 and C447, respectively, but 0.750 (6) Å for atom C347. At the same time, the pairs of exocyclic O-C-C angles at C144 and C244 in (I), and at C144, C244 and C444 in (II) all differ by ca 10 . This behaviour is characteristic of planar and near-planar alkoxyarenes (Seip & Seip, 1973;Ferguson et al., 1996;Kiran Kumar et al., 2020). On the other hand, the difference between the exocyclic angles at atom C344 in (II) is only 6.7 (5) .

Supramolecular features
The supramolecular assembly of compound (I) is di-periodic (propagates in two-dimensions) and is built from a combination of O-HÁ Á ÁO, N-HÁ Á ÁO, C-HÁ Á ÁO and C-HÁ Á Á(arene) hydrogen bonds (Table 1). However, the assembly can readily be analysed in terms of a number of simple substructures (Ferguson et al., 1998a,b;Gregson et al., 2000). The two independent anions and the two independent water molecules are linked by O-HÁ Á ÁO hydrogen bonds to form a C 4 4 (12) Etter et al., 1990;Bernstein et al., 1995) chain running parallel to the [010] direction (Fig. 4). Inversion-related pairs of chains of this type are linked by the two types of cation to form a molecular ribbon in the form of a chain of edge-fused R 7 8 (20) rings parallel to [010] along the line (1, y, 0.5) (Fig. 5). The ribbons along [010] are linked into Table 1 Hydrogen-bond geometry (Å , ) for (I).

Figure 4
Part of the crystal structure of compound (I) showing the formation of a C 4 4 (12) chain of two types of anion and two types of water molecule running parallel to [010]. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the cations and the H atoms bonded to C atoms in the anions have been omitted.

Figure 5
Part of the crystal structure of compound (I) showing the formation of a ribbon of R 7 8 (20) rings running parallel to [010]. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the H atoms bonded to C atoms have been omitted.
sheets lying parallel to (001) by a combination of C-HÁ Á ÁO and C-HÁ Á Á(arene) hydrogen bonds, and it is convenient to consider separately the sub-structures formed by these two types of interaction. In the simpler of these two sub-structures, (Fig. 6), inversion-related ion pairs are linked by C-HÁ Á ÁO hydrogen bonds (Table 1) to form an R 2 4 (10) ring, which links the chains along (1, y, 0.5) and (0, y, 0.5). The second substructure ( Fig. 7) contains C-HÁ Á Á(arene) hydrogen bonds and also includes water molecules but, again, it links the chains along (1, y, 0.5) and (0, y, 0.5). Propagation of these motifs by inversion thus links adjacent [010] chains into a complex sheet lying parallel to (001).
There are eight independent N-HÁ Á ÁO hydrogen bonds in the structure of compound (II) ( Table 2). Four of these lie within the two ion triplets that were selected as the asymmetric unit (Figs. 2 and 3), and the other four act to link the type 1 and type 2 triplets into sheets of alternating R 4 4 (18) and R 10 12 (38) rings lying parallel to (001) (Fig. 8). Two sheets of this type, which are related to one another by the action of the 2 1 screw axis, pass through each unit cell, in the domains 0.25 < z < 0.75 and 0.75 < z < 1.25, but there are no direction-specific interactions between adjacent sheets: the C-HÁ Á ÁO and C-HÁ Á Á(arene) hydrogen bonds all lie within a single sheet.

Database survey
In addition to the structures of a number of salts formed between N-(4-methoxyphenyl)piperazine and carboxylic acids (Kiran Kiran Kumar, Yathirajan, Sagar et al., 2019), structures have also been reported for the chloride (Zia-ur-Rehman et al., 2009) and tetra(isothiocyanato)cobaltate(II) salts (Gharbi et al., 2021). By contrast, the only structures reported for salts of the isomeric N-(3-methoxyphenyl)piperazine are those of the maleate (Verdonk et al., 1997) and the 4-(3-methoxyphenyl)piperazin-1-carboxylate (Ö zdemir, 2021). In addition to the structures reported for the picrate (Verdonk et al., 1997)  Part of the crystal structure of compound (I) showing the formation of a ring containing O-HÁ Á ÁO, N-HÁ Á ÁO and C-HÁ Á Á(arene) hydrogen bonds that link adjacent [010] chains. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the H atoms bonded to those C atoms that are not involved in the motif shown have been omitted. The atoms marked with an asterisk (*) are at the symmetry position (1 À x, 1 À y, 1 À z). Table 2 Hydrogen-bond geometry (Å , ) for (II).

Figure 8
A schematic representation of part of the crystal structure of compound (II) showing the formation of a sheet of R 4 4 (18) and R 10 12 (38) rings. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the H atoms of the anions have been omitted and only the NH 2 groups of the cations are shown.

Figure 6
Part of the crystal structure of compound (I) showing the formation of an R 2 4 (10) ring linking adjacent [010] chains. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the H atoms bonded to those C atoms that are not involved in the motif shown have been omitted. The atoms marked with an asterisk (*) are at the symmetry position (1 À x, Ày, 1 À z).

Data collection and structure refinement
Crystals of (I) shattered on cooling to 90 K, while those of compound (II) showed faint satellite reflections at 90 K that gradually diminished in intensity on warming. At the data collection temperature of 180-K, crystals of (I) remained intact and the satellite reflections observed for (II) were absent. Crystal data, data collection and refinement details are summarized in Table 3. All H atoms were located in difference maps. The H atoms bonded to C atoms were then treated as riding atoms in geometrically idealised positions with C-H distances 0.95 Å (aromatic), 0.98 Å (CH 3 or 0.99 Å (CH 2 ), and with U iso (H) = kU eq (C), where k = 1.5 for the methyl groups, which were permitted to rotate but not to tilt, and 1.2 for all other H atoms bonded to C atoms. For the H atoms bonded to N or O atoms, the atomic coordinates 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 and 2. For compound (II), Cu K radiation was used to facilitate establishing a unique orientation for the structure with respect to the polar axis direction. For the crystal selected for data collection, however, the value of the Flack x parameter (Flack, 1983), obtained in the conventional way via full-matrix least-squares refinement, i.e. x = 0.45 (18) was inconclusive due to its high standard uncertainty, while that calculated using 4511 quotients (Parsons et al., 2013)   For both structures, data collection: APEX3 (Bruker, 2016); cell refinement: APEX3 (Bruker, 2016); data reduction: APEX3 (Bruker, 2016); program(s) used to solve structure: SHELXT2014/5 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: PLATON (Spek, 2020); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015b) and PLATON (Spek, 2020).

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.