Crystal structure studies of 4-ethylpiperazin-1-ium 3,5-dinitrobenzoate, 4-methylpiperazin-1-ium 3,5-dinitrobenzoate and 4-methylpiperazin-1-ium 4-iodobenzoate

Three novel piperazinium salts are described. Their crystal structure is based on layers formed by hydrogen bonding, halogen bonding and other weak interactions. One exhibits an asymmetric unit containing a 1-ethylpiperazinium cation and a 3,5-dinitrobenzoate anion while the other two salts have asymmetric units containing 1-methylpiperazinium as a common cation and a 3,5-dinitrobenzoate anion or a 4-iodobenzoate anion.


Chemical context
Piperazines and substituted piperazines are important pharmacophores that can be found in many biologically active compounds across a number of different therapeutic areas (Berkheij, 2005) such as antifungal (Upadhayaya et al., 2004), anti-bacterial, anti-malarial and anti-psychotic agents (Choudhary et al., 2006). A valuable insight into recent advances on antimicrobial activity of piperazine derivatives has been reported (Kharb et al., 2012).
Piperazines are among the most important building blocks in today's drug discovery efforts and are found in biologically active compounds across a number of different therapeutic areas (Brockunier et al., 2004;Bogatcheva et al., 2006). A review of the current pharmacological and toxicological information for piperazine derivatives is given by Elliott (2011).

Structural commentary
The molecular structures of the title salts (I), (II) and (III) are illustrated in Figs. 1, 2 and 3, respectively. The asymmetric unit of compound (I) is composed of one 1-ethylpiperazinium cation and one 3,5-dinitrobenzoate anion while (II) consists of a 1-methylpiperazinium cation and a 3,5-dinitrobenzoate anion. Compound (III) crystallizes with one 1-methylpiperazinium cation and one 4-iodobenzoate anion in the asymmetric unit. In all compounds, the piperazine rings have a The molecular structure of compound (II), showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Figure 1
The molecular structure of compound (I), showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level. chair conformation with a positively charged protonated N atom with a maximum deviation from their mean plane of 0.239 (2), 0.258 (2) and 0.238 (2) Å at atom N1, for the three title compounds, respectively. The benzene rings are almost planar, with maximum deviations of 0.010 (2), 0.006 (2) and 0.006 (3) Å at atoms C8, C10 and C8 for (I), (II) and (III) respectively. The substituents of the benzene rings in all compounds are approximately in the same plane and do not deviate significantly from planarity.

Supramolecular features
In the crystal of (I), the cation and anion are linked by N2-H21Á Á ÁO1 hydrogen bonds, forming layers extending along the Molecular packing of (I) with hydrogen bonding shown as dashed lines. Table 1 Hydrogen-bond geometry (Å , ) for (I).  Table 2 Hydrogen-bond geometry (Å , ) for (II).

Figure 5
Molecular packing of (II) with hydrogen bonding shown as dashed lines..

Figure 6
Molecular packing of (III) with hydrogen bonding shown as dashed lines..

Figure 3
The molecular structure of compound (III), showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Database survey
A search of the Cambridge Structural Database (Version 2020.3.0, last update March 2021; Groom et al., 2016) for the piperazinium cation and benzoate anion involved in the three salts gave 62 hits, 60 of which have branched aromatic substituents either on the piperazinium cation, the benzoate anion or both, that make their structures extremely different from those of the title salts. The other two compounds are quite similar to the title molecules: 4-methylpiperazin-1-ium 2amino-5-iodobenzoate (MAVMEC: Zhu & Guo, 2005) and 1methylpiperazine-1,4-diium 4-nitrophthalate(2-) 4-nitrophthalic acid monohydrate (IZEFY: Guo, 2004), which share the cationic part and its chair conformation with salts (II) and (III). The crystal structures of the two compounds are based on differently sized rings formed through hydrogen-bond contacts, which then aggregate into a 3D framework.

Synthesis and crystallization
For the synthesis of (I), a solution of commercially available 1ethylpiperazine (100 mg, 0.88 mol) (from Sigma-Aldrich) in methanol (10 ml) was mixed with an equimolar solution of 3,5dinitrobenzoic acid (186.6 mg, 0.88 mol). Compounds (II) and (III) were prepared by the same method in which 1-methylpiperazine (100 mg, 1.0 mol) in methanol (10 ml) was mixed with an equimolar solution of 3,5-dinitrobenzoic acid (212 mg, 1.0 mol) for (II) or with an equimolar solution of 4-iodobenzoic acid (248 mg, 1.0 mol) for (III). The corresponding mixtures were stirred for 30 min at 323 K and allowed to stand at room temperature. X-ray quality crystals were formed upon slow evaporation in a week time (m.p. 453-455 K, 459-461 K and 410-412 K, respectively).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 4. The H atoms bound to C were positioned with idealized geometry and refined using a riding model with aromatic C-H = 0.93 Å , 0.96 Å (methyl) or 0.97 Å (methylene). The H atoms of the N atom were located in a difference map and later restrained to the distance N-H = 0.86 (2) Å . All H atoms were refined with isotropic displacement parameters set at 1.2U eq (C-aromatic, C-methylene, N) or 1.5U eq (C-methyl) of the parent atom. SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: Mercury (Macrae et al., 2020); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015b), PLATON (Spek, 2020) and publCIF (Westrip, 2010). where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.20 e Å −3 Δρ min = −0.17 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.

4-Methylpiperazin-1-ium 3,5-dinitrobenzoate (II)
Crystal data where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.28 e Å −3 Δρ min = −0.15 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq O1 0.4259 (

4-Methylpiperazin-1-ium 4-iodobenzoate (III)
Crystal data where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.37 e Å −3 Δρ min = −0.95 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.