Stoichiometric and polymorphic salts of hexamethylenetetraminium and 2-chloro-4-nitrobenzoate

Four molecular salts made from hexamethylenetetraminium and 2-chloro-4-nitrobenzoate have been synthesized and are reported. All four molecular salts show N+—H⋯O− hydrogen bonding. This work shows that hmta only protonates once, even in the presence of excess acid.


Chemical context
Crystal engineering, the conception and synthesis of molecular solid-state structures, is fundamentally based upon the discernment and subsequent exploitation of intermolecular interactions (Desiraju, 1989) Thus, primarily non-covalent bonding is used to achieve the organization of molecules and ions in the solid state in order to produce materials with desired properties. One molecule that has been used that has multiple acceptor sites is hexamethylenetetramine (hmta), and it has been shown to act as a hydrogen-bond acceptor for alcohol or carboxylic acid donors (Lemmerer, 2011). Interestingly, hmta has four equivalent N atoms but there are very few reported co-crystals or salts that use all four. Examples that use all four N atoms in neutral hydrogen bonding are seen with alcohols (MacLean et al., 1999), whereas the vast majority of molecular complexes with hmta show it acting as a twofold acceptor (Li et al., 2001). However, if protonation does occur, then it is usually confined to only one site being protonated (Lemmerer et al., 2012). 2-Chloro-4-nitrobenzoic (2c4nH) acid has been used extensively in making co-crystals and salts using pyridine as an acceptor (Lemmerer et al., 2010(Lemmerer et al., , 2015 and has been chosen to be the hydrogen-bond donor/acid. The experimental pK a of hmta is 4.89 (Cooney et al., 1986), and the calculated pK a of 2c4nH is 2.04 (Lemmerer et al., 2015). Childs et al. (2007) postulated that for 0 < ÁpK a < 3, either a neutral co-crystal or salt can form, and that the crystalline environment can influence which one is favoured. In general, however, for ÁpK a values > 3 and < 0, a salt or co-crystal, respectively, is formed (Lemmerer et al., 2015). Hence, it is ISSN 2056-9890 postulated that proton transfer will occur for a solution containing hmta and 2c4nH. In this work, we will make molecular salts using a 1:1 or 1:2 ratio of hmta with 2c4nH to see if two N atoms sites can be protonated. The four salts synthesized and reported here are: (hmtaH + )Á(NH 4 + )(2c4nH À ) 2 , (I), (hmtaH + )Á(2c4nH À ) 2 , (II) and (hmtaH + )Á(2c4nH À ), (IIIa) and (IIIb).

Structural commentary
The asymmetric units and atom-labelling schemes are shown in Fig. 1, together with their displacement ellipsoids for all four salts. A noteworthy asymmetric unit is the one for salts (I) and (II). In salt (I), there is the expected simple hmtaH + cation and 2c4n À pair that are hydrogen bonded to each other using a charge-assisted N + -HÁ Á ÁO À hydrogen bond (Table 1). However, an NH 4 + ammonium cation is included in the asymmetric unit and its charge is balanced by a second 2c4n À anion. The NH 4 + cation's appearance is not unique as it has been reported in the literature that hmta can decompose to form NH 4 and formaldehyde (Lough et al., 2000), especially if the crystallization takes place slowly and in the presence of an acid. From a crystallographic standpoint, the 2:1 molecular salt (II) features half of an hmtaH + cation crystallizing along a mirror plane at y = 1/4 and a fully occupied 2c4nH anion. In the difference-Fourier map, there is clear evidence that the N1 atom on a special position (0.485286 0.250000 0.494001) is protonated and hence has a half positive charge. However, the carboxylic acid group of 2c4nH has bond lengths typical of being neutral and clearly shows an acidic H atom, H2, located near O1 in the difference-Fourier map. Combined, this means that H1 acts as a bifurcated donor to two 2-chloro-4-nitrobenzoic molecules (Table 2), which themselves share the hydrogen atom H2. Molecular salts (IIIa) and (IIIb) both have a 1:1 ratio and are polymorphs of each other. Both have charge-assisted N + -HÁ Á ÁO À hydrogen bonds (Tables 3 and 4) between the two ions but differ in their packing as described further below.

Supramolecular features
The packing of salt (I) consists of clearly separated layers of hydrophobic and hydrophillic layers. All good hydrogen-bond donors are used (Table1, Fig. 2a). The NH 4 + cation forms a hydrogen-bonded ring using two carboxylate groups and this ring repeats along the b-axis direction. The ring can be described as R 3 4 (8) and is a common feature in ammonium carboxylate salts (Lemmerer & Fernandes, 2012). This ladder is then surrounded by a 2c4n À anion that hydrogen bonds to the hmta + cation. Overall, the hydrophilic layer consists of the cationic NH part of hmtaH + , NH 4 + and the carboxylate CO 2 À part of 2c4n À (Fig. 3a). Salt (II) consists only of the hmtaH + and 2c4n À anion in a 1:2 ratio. However, it appears crystallographically that only one complete proton transfer has taken  Table 1 Hydrogen-bond geometry (Å , ) for (I).  (2) 173 (2) Symmetry codes: (i) Àx þ 1 2 ; y þ 1 2 ; Àz þ 1 2 ; (ii) x; y þ 1; z. Table 2 Hydrogen-bond geometry (Å , ) for (II).  Hydrogen-bond geometry (Å , ) for (IIIa). (2) 173 (3) Table 4 Hydrogen-bond geometry (Å , ) for (IIIb). 175.7 (19) place, and that on average, each of the 2c4n anions has released half a proton each to the N atom (labelled H1) and that the other half proton (labelled as H2) is located in between the two anions. Hence, only one N atom on hmta has been protonated, and subsequently, two 2c4n À anions are behaving as acceptors from a single N-H group (Fig. 1). Overall, the same layering of hydrophilic and hydrophobic parts occurs, where the cationic and anionic parts are located in the same ac plane. Salts (IIIa) and (IIIb) have identical asymmetric units with a 2:1 ratio of hmtaH + and 2c4n À , in contrast to the previous two salts. The only significant difference is in the relative packing of these ion pairs. In (IIIa), the pairs pack anti-parallel (Fig. 3c), and in (IIIb), parallel ( Fig. 3d).

Database survey
Up to now, there are only 36 structures of singly protonated hmtaH + molecular salts in the Cambridge Structural Database (CSD, Version 5.38;Groom et al., 2016), together with any organic or inorganic counter-anion. Only one structure has the hmta doubly protonated (FOQZIW;Zaręba et al., 2014). Cocrystals of hmta in a 1:1 or 1:2 ratio with carboxylic acids are much more numerous (45). Ultimately, it has been shown that even with an excess of 2c4n, the hmta molecule only allows itself to be protonated once.

Refinement details
Crystal data, data collection and structure refinement details are summarized in Table 5. For all compounds, the C-bound H atoms were placed geometrically (C-H bond lengths of 0.99 (ethylene CH 2 ), and 0.95 (Ar-H) Å ) and refined as riding with U iso (H) = 1.2U eq (C). The N-bound H atoms were located in difference-Fourier maps and their coordinates and isotropic displacement parameters allowed to refine freely. The Obound H atom in (II) was located in the difference-Fourier map and refined as riding with U iso (H) = 1.5U eq (O).  The packing diagrams for all four salts. Note the different packing arrangement of the two 1:1 dimorphs (IIIa) and (IIIb).

Special details
Experimental. Numerical integration absorption corrections based on indexed crystal faces were applied using the XPREP routine (Bruker, 2007) 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
Experimental. Numerical integration absorption corrections based on indexed crystal faces were applied using the XPREP routine (Bruker, 2016) 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
Experimental. Numerical integration absorption corrections based on indexed crystal faces were applied using the XPREP routine (Bruker, 2007) 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 C1  where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.55 e Å −3 Δρ min = −0.32 e Å −3 Special details Experimental. Numerical integration absorption corrections based on indexed crystal faces were applied using the XPREP routine (Bruker, 2016) 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.