Two 3-amino-1H-pyrazol-2-ium salts containing organic anions, and an orthorhombic polymorph of 3-amino-1H-pyrazol-2-ium nitrate

The hydrogen-bonded assembly of 3-amino-1H-pyrazol-2-ium 3,5-dinitrobenzoate monohydrate and bis(3-amino-1H-pyrazol-2-ium) fumarate fumaric acid is two-dimensional, but that in the orthorhombic form of the simple salt 3-amino-1H-pyrazol-2-ium nitrate is three-dimensional.


Chemical context
Pyrazoles exhibit a very wide range of pharmacological and other biological activities, which have recently been extensively reviewed (Ansari et al., 2017;Karrouchi et al., 2018). Derivatives derived from 3-amino-1H-pyrazole have been reported as tyrosine kinase inhibitors, of potential use in cancer treatment (Feng et al., 2008) and as inhibitors of the intracellular phosphorylation of the heat-shock protein hsp27 (Velcicky et al., 2010). As part of a general study of novel pyrazole derivatives (Asma et al., 2018;Kiran Kumar et al., 2020;Shaibah et al., 2020a,b;Shreekanth et al., 2020), we have now synthesized two organic salts derived from 3-amino-1Hpyrazole, namely 3-amino-1-pyrazol-2-ium 3,5-dinitrobenzoate monohydrate (I) ( Fig. 1 and Scheme) and bis(3-amino-1pyrazol-2-ium) fumarate fumaric acid (II) (Fig. 2), whose molecular and supramolecular structures are reported here. Compounds (I) and (II) were readily prepared by co-crystallization of 3-amino-1H-pyrazole with an equimolar quantity of the appropriate organic acid. We have also isolated a second polymorph of 3-amino-1-pyrazol-2-ium nitrate (III). When crystallized from methanol, this compound forms an orthorhombic polymorph in space group Pna2 1 ; a monoclinic polymorph in space group P2 1 /c, isolated from aqueous solution has recently been reported (Yamuna et al., 2020). Here we ISSN 2056-9890 discuss the molecular and supramolecular structures of both polymorphs of the nitrate salt.

Structural commentary
The salt 3-amino-1H-pyrazol-2-ium 3,5-dinitrobenzoate crystallizes from methanol as a monohydrate, although methanol is absent from the crystal structure. The constitution of the salt (I) derived from fumaric acid is more complex: the structure contains a single cation, occupying a general position, along with a fumarate dianion and a neutral fumaric acid molecule, each lying across a centre of inversion, selected as those at (0.5, 0.5, 0.5) and (0.5, 0, 0.5), respectively, for the anionic and neutral components. The correct location of the H atom bonded to atom O31 (Fig. 2) was confirmed not only by refinement of the atomic coordinates for this H atom and by the final difference map, but also by the C-O distances in the two fumaric acid units, thus 1.2472 (17) and 1.2525 (15) Å in the anion, and 1.2136 (17) and 1.3065 (18) Å in the neutral fumaric acid molecule. Although the co-existence of equal numbers of fumarate anions and neutral fumaric acid molecules, as opposed to hydrogenfumarate anions, seems at first sight unexpected or even counter-intuitive, in fact a number of structures have been reported in which this combination is present, as noted below in Section 4.
Isolation of the nitrate salt from a methanol solution produces an orthorhombic form with space group Pna2 1 ; it has research communications Figure 3 The independent components in compound (III) showing the atomlabelling scheme and the hydrogen bonds within the selected asymmetric unit. Displacement ellipsoids are drawn at the 30% probability level.

Figure 1
The independent components in compound (I) showing the atomlabelling scheme and the hydrogen bonds within the selected asymmetric unit. Displacement ellipsoids are drawn at the 30% probability level.

Figure 2
The independent components in compound (II) showing the atomlabelling scheme and the hydrogen bonds within the selected asymmetric unit. Displacement ellipsoids are drawn at the 30% probability level, and the atoms marked with the suffix 'a' or 'b' are at the symmetry positions (1 À x, 1 À y, 1 À z) and (1 À x, Ày, 1 À z), respectively. recently been reported [Yamuna et al., 2020;CSD (Groom et al., 2016) refcode NUKKOW], that crystallization of the nitrate salt from an aqueous solution provides a monoclinic polymorph with space group P2 1 /c, which it is convenient to denote here as (IIIa). There is no obvious simple relationship between either the direct or the reduced cell dimensions for these two polymorphs.
For each of (I)-(III) it is possible to selected a compact asymmetric unit in which the components are linked by N-HÁ Á ÁO hydrogen bonds (Figs. 1-3). Within the asymmetric unit of (II), there is a fairly short but markedly asymmetric O-HÁ Á ÁO hydrogen bond (Table 2) linking the anionic and neutral fumaric fragments.
The bond distances within the cations exhibit some interesting features. In neutral 1H-pyrazole, the bonds corresponding to N12-C13 and C14-C15 in compounds (I)-(III) (cf. Figs. 1-3) are formally double bonds, while the other ring bonds are all formally single bonds. However, as shown in Table 1, which also includes data for the monoclinic polymorph (IIIa) (Yamuna et al., 2020) for comparison, in none of the cations discussed here does the range of the C-N distances exceed 0.03 Å , while the difference between the two C-C distances never exceeds 0.04 Å . These observations indicate that the positive charge is delocalized over all three of the N atoms, such that all three canonical forms (A)-(C)  Table 1 Selected bond distances (Å ).
The data for the monoclinic polymorph (IIIa) are taken from Yamuna et al. (2020), but with the atom labels adjusted to match those used for (I)-(III).

Supramolecular features
The supramolecular assembly in compounds (I)-(III) is dominated by N-HÁ Á ÁO Hydrogen bonds together with O-HÁ Á ÁO hydrogen bonds in (I) and (II) ( Table 2). For the twocentre interactions, those having D-HÁ Á ÁA angles significantly less than 140 have been discounted, as the associated interaction energies are likely to be negligible (Wood et al., 2009). Such contacts are better regarded as adventitious contacts that arise within the supramolecular arrangements dominated by the significant hydrogen bonds. The two ionic components in compound (I) are linked by two N-HÁ Á ÁO hydrogen bonds, forming an R 2 2 (8) ring (Etter, 1990;Etter et al., 1990;Bernstein et al., 1995), and a third N-HÁ Á ÁO links the water component to the ion pair, forming a three-component aggregate (Fig. 1). The hydrogen-bonded supramolecular assembly in compound (I) is two-dimensional. The O-HÁ Á ÁO hydrogen bond involving atom H31 (Table 2) links the aggregates which are related by translation along [010] to form a C 3 3 (9)C 3 3 (9)[R 2 2 (8)] chain of rings. In addition, the N-HÁ Á ÁO hydrogen bond involving atom H132 links the ion pairs that are related by translation along [001] into a C 2 2 (10)C 2 2 (12)[R 2 2 (8)] chain of rings. The combination of these two chain motifs generates a sheet lying parallel to (100) and containing R 2 2 (8) and R 7 8 (32) rings (Fig. 5). Finally, the second O-HÁ Á ÁO hydrogen bond involving atom H32 links pairs of such sheets, which are related by inversion, to form a complex bilayer.
The supramolecular assembly in compound (II) is relatively straightforward. The single O-HÁ Á ÁO hydrogen bonds links the fumarate ions and the fumaric acid molecules into a chain running parallel to the [010] direction, in which the anions and neutral molecules alternate (Fig. 6). Two chains of this type, which are related to one another by the c-glide planes, pass through each unit cell and they are linked by the cations, via a combination of N-HÁ Á ÁO hydrogen bonds, to form a sheet lying parallel to (102), within which rings of R 1 2 (6), R 2 2 (6), R 2 2 (7) and R 4 5 (22) types are present (Fig. 7). The ionic components in compound (III) are linked by two N-HÁ Á ÁO hydrogen bonds to form an ion pair containing an Part of the crystal structure of compound (II), showing the formation of a chain of alternating fumarate ions and fumaric acid molecules. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the cations and the H atoms bonded to C atoms have been omitted. The atoms marked with an asterisk (*), a hash (#), a dollar sign ($) or an ampersand (&) are at the symmetry positions (1 À x, 1 À y, 1 À z), (1 À x, Ày, 1 À z), (x, 1 + y, z) and (1 À x, 2 À y, 1 À z), respectively. The atoms O21 and O31 (without symmetry symbols) are components of the reference species at (x, y, z).

Figure 5
Part of the crystal structure of compound (I), showing the formation of a hydrogen-bonded sheet lying parallel to (100). Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the H atoms bonded to C atoms have been omitted.
R 2 2 (8) ring (Fig. 3). Ion pairs of this type are linked by one twocentre N-HÁ Á ÁO hydrogen bond and one three-centre N-HÁ Á Á(O) 2 system into a three-dimensional framework structure, whose formation is readily analysed in terms of three simple one-dimensional sub-structures (Ferguson et al., 1998a,b;Gregson et al., 2000). The two-centre N-HÁ Á ÁO hydrogen bond, acting alone, links ion pairs that are related by the 2 1 screw axis along [001], forming a C 2 2 (7)C 2 2 (9)[R 2 2 (8) chain of rings running parallel to [001] (Fig. 8). The three-centre N-HÁ Á Á(O) 2 hydrogen bond links ion pairs that are related by the n-glide plane to form a chain of alternating R 2 1 (4) and R 2 2 (8) rings running parallel to the [011] direction ( Fig. 9). When the two-centre and three-centre systems act alternately, they link the ion pairs into a chain of rings running parallel to the [102] 38 Part of the crystal structure of compound (III), showing the formation of a 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 7
Part of the crystal structure of compound (II), showing the formation of a sheet lying parallel to (102). Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the cations and the H atoms bonded to C atoms have been omitted.

Figure 9
Part of the crystal structure of compound (III), showing the formation of a chain of rings running parallel to [011]. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the H atoms bonded to C atoms have been omitted. direction (Fig. 10). The combination of the chains along [001], [011] and [102] suffices to link all of the components into a three-dimensional framework structure.

Database survey
As noted above in Section 2, a monoclinic polymorph of the nitrate salt, denoted (IIIa) has recently been reported, but without any analysis or description of the supramolecular assembly (Yamuna et al., 2020). As found in the orthorhombic polymorph (III), the ions in (IIIa) are linked by two N-HÁ Á ÁO hydrogen bonds to form an ion pair characterized by an R 2 2 (8) motif. Two further N-HÁ Á ÁO hydrogen bonds link these ion pairs into a sheet lying parallel to (102), in which rings of R 2 2 (8), R 4 4 (14) and R 6 8 (26) types are present (Fig. 11). Sheets of this type are linked by a C-HÁ Á ÁO hydrogen bond to form a three-dimensional framework structure. In the picrate salt, the ions are linked into sheets by a combination of N-HÁ Á ÁO and C-HÁ Á ÁO hydrogen bonds (Infantes et al., 1999). In the hydrogen succinate salt, a combination of O-HÁ Á ÁO and N-HÁ Á ÁO hydrogen bonds links the ions into sheets containing R 2 2 (8), R 2 3 (12) and R 4 5 (20) rings (Yamuna et al., 2014). The structure of the trifluoroacetate, which crystallizes with Z 0 = 2, and with disorder in each of the independent anions, contains only N-HÁ Á ÁO hydrogen bonds, which link the ions into complex sheets (Yamuna et al., 2013). We also note that the structure of tetrakis(3-amino-1H-pyrazol-2-ium) bis(-chloro)octachlorodibismuth, (C 3 H 6 N 3 ) 4 (Bi 2 Cl 10 ), has been reported (Ferjani & Boughzala, 2018).
A number of structures have been reported in which fumarate dianions co-exist in equal numbers with neutral fumaric acid molecules, as found here for compound (II).

Synthesis and crystallization
The synthesis of compounds (I)-(III) employed commercially available 3-amino-1H-pyrazole, which was used as received. For the synthesis of compounds (I) and (II), a solution of 3-amino-1H-pyrazole (100 mg, 1.20 mmol) in ethanol (10 ml) was mixed with a solution of the appropriate acid, 3,5-dinitrobenzoic acid (255 mg, 20 mmol) for (I) or fumaric acid (139 mg, 1.20 mmol) for (II), also in methanol (10 ml Part of the crystal structure of the monoclinic polymorph (IIIa) of 3-amino-1H-pyrazol-2-ium nitrate showing the formation of a hydrogenbonded sheet parallel to (102). The deposited coordinates (Yamuna et al., 2020) have been used. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the H atoms bonded to C atoms have been omitted.

Figure 10
Part of the crystal structure of compound (III), showing the formation of a chain of rings running parallel to [102]. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the H atoms bonded to C atoms have been omitted.
(100 mg, 1.20 mmol) in ethanol (10 ml). Each of these mixtures was stirred at ambient temperature for 15 min and then set aside to crystallize at ambient temperature and in the presence of air. After one week, the resulting crystals were collected by filtration and dried in air: m.p. (I) 418-423 K, (II) 383-388 K, (III) 385-390 K. Crystals suitable for single-crystal X-ray diffraction were selected directly from the prepared samples.

Refinement
Crystal data, data collection and refinement details are summarized in Table 3. For compound (I), one low-angle reflection (1,0,0) that had been attenuated by the beam stop was omitted from the refinement. All H atoms were located in difference 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 and U iso (H) = 1.2U eq (C). 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). In the absence of significant resonant scattering, it was not possible to determine the correct orientation of the structure of (III) relative to the polar axis direction, although this has no chemical significance.   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. where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.15 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.