Crystal structure of the co-crystal salt 2-amino-6-bromopyridinium 2,3,5,6-tetrafluorobenzoate

The title compound crystallized from an equimolar mixture of 2-amino-6-bromopyridine and 2,3,5,6-tetrafluorobenzoic acid in absolute ethanol.

The asymmetric unit of the co-crystal salt 2-amino-6-bromopyridinium 2,3,5,6tetrafluorobenzoate, C 5 H 6 BrN 2 + ÁC 7 HF 4 O 2 À , contains one pyridinium cation and one benzoate anion. In the crystal, the aminopyridinium cationic unit forms two hydrogen bonds to the benzoate oxygen atoms in an R 2 2 (8) motif. Two pyridinium benzoate units are hydrogen bonded through self-complementary hydrogen bonds between the second amine hydrogen and a carboxylate O with a second R 2 2 (8) motif to form a discrete hydrogen-bonded complex containing two 2-amino-6-bromopyridinium moieties and two 2,3,5,6-tetrafluorobenzoate moieties. The 2-amino-6-bromopyridinium moieties -stack in a head-to-tail mode with a centroid-centroid separation of 3.7227 (12) Å and adjacent tetrafluorobenzoates also -stack in a head-to-tail mode with a centroidcentroid separation of 3.6537 (13) Å .

Chemical context
The fields of crystal engineering and supramolecular chemistry rely on the identification and application of versatile synthons to guide the construction of molecular solids (Desiraju, 1995(Desiraju, , 2013. For example carboxylic acids are known to form a centrosymmetric dimer through self-complementary O-HÁ Á ÁO hydrogen bonds (Fig. 1a) in addition to hydrogenbonded catemer chains and rings. It has been shown that these hydrogen bonds can be diverted by O-HÁ Á ÁN hydrogen bonding to pyridines, often supported by a non-conventional pyridine C-HÁ Á ÁO hydrogen bond (Fig. 1b). The interaction of the more basic pyridines, for example 4-(N,N-dimethylamino)pyridine, with carboxylic acids most often yields charge-assisted hydrogen-bonded salts (Fig. 1c). Similarly, the combination of 2-aminopyridines and benzoic acids has been ISSN 2056-9890

Figure 1
Potential hydrogen-bonding motifs for (a) carboxylic acid dimers, (b) neutral hydrogen-bonded pyridine carboxylic acid co-crystals, (c) chargeassisted pyridinium carboxylate hydrogen-bonded complexes, and (d) charge-assisted 2-aminopyridinium carboxylate hydrogen-bonded complexes. demonstrated to be a reliable supramolecular synthon resulting in the formation of charge-assisted hydrogen-bonded complexes shown in Fig. 1d (Bis & Zaworotko, 2005). The formation of hydrogen-bonded co-crystals or salts of amines and acids has potential in the pharmaceutical field where the physicochemical properties of active pharmaceuticals, including aqueous solubility and physical and chemical stability, may be modulated and tailored by co-crystal or salt formation (Schultheiss & Newman, 2009). For example a study involving the non-steroidal anti-inflammatory drug piroxicam reported the formation of 19 pyridine based co-crystals (Wales et al., 2012). The present study presents the first co-crystal/salt formed between a substituted pyridine and 2,3,5,6-tetrafluorobenzoic acid.

Structural commentary
The asymmetric unit of the co-crystal salt 2-amino-6-bromopyridinium 2,3,5,6-tetrafluorobenzoate (I), contains one pyridinium cation and one benzoate anion that are held together by two charge-assisted hydrogen bonds (Table 1, first two entries) to form an R 2 2 (8) motif (Fig. 2). The bond distance C12-O2 is slightly shorter than C12-O1, with distances of 1.236 (2) and 1.267 (2) Å respectively. The atoms that form this R 2 2 (8) motif ( Fig. 1) are almost coplanar, with the maximum deviation above and below the least-squares plane calculated through all of these atoms being 0.169 (7) and À0.147 (8) Å , respectively, for O2 and O1. The angle between the planes defined by the benzene and pyridine rings is 67.04 (7) and the carboxylate anion is twisted out of the plane of the benzene ring, with C12 0.103 (3) Å above the plane of the benzene ring and O1 1.043 (3) Å above, and O2 0.713 (4) Å below the plane defined by the benzene ring.

Supramolecular features
In the co-crystal salt (I), adjacent amino pyridinium benzoate salt units are linked into dimeric salt complexes with selfcomplementary hydrogen bonds (Table 1, entry 3) from the second amine hydrogen atom and carboxylate oxygen atom O2 in a second R 2 4 (8) motif (Fig. 3). The two components are relatively well separated within the crystal structure into zones parallel to the c axis.

Figure 2
The molecular structure of the co-crystal salt (I) showing the atomlabeling scheme. Displacement ellipsoids drawn at the 50% probability level and hydrogen bonds (Table 1) are shown as dotted lines.

Figure 3
Part of the crystal structure of (I) viewed along b, highlighting the hydrogen-bonded dimeric salt unit.

Figure 4
Partial view of the packing in the crystal structure of (I) highlighting the head-to-tail -stacking of the tetrafluorobenzoate molecules and the C-FÁ Á Á interaction.

Database survey
A search of the Cambridge Crystallographic Database (Version 5.39, update of August 2018; Groom et al., 2016) using Conquest (Bruno et al., 2002) for structures including the neutral carboxylic acid dimer synthon as shown in Fig. 1a revealed 6,016 hits, while a search for neutral pyridine carboxylic acid interactions where the distance between the acid proton and the pyridine N is equal to or less than the sum of the van der Waals radii revealed 2189 hits. In 966 of the 2189 structures the distance between the carbonyl O and the pyridine H is also equal to or less than the sum of the van der Waals radii, corresponding to the synthon shown in Fig. 1b. A related search of the Cambridge Crystallographic Database for co-crystals with 4-(N,N-dimethylamino)pyridine and carboxylic acids revealed only four neutral co-crystals and 54 structures corresponding to the pyridinium carboxylate as shown in Fig. 1c. A similar search for co-crystals formed between 2-aminopyridines with benzoic acids yielded 41 hits, of which 40 feature charge-assisted aminopyridinium carboxylate hydrogen-bonded co-crystals as the result of proton transfer shown in Fig. 1d. The structure that is reported to form a neutral hydrogen-bonded complex corresponds to the co-crystal formed between 2-aminopyridine and 4-aminobenzoic acid [refcode WOPCOV; Chandrasekaran & Babu, 2014]. Finally there is only one reported co-crystal of 2,3,5,6-tetrafluorobenzoic acid, or the corresponding 2,3,5,6-tetrafluorobenzoate, with an organic base. In that example theophylline forms a neutral hydrogen-bonded complex (Corpinot et al., 2016).

Synthesis and crystallization
2-Amino-6-bromopyridine and 2,3,5,6-tetrafluorobenzoic acid were used as supplied. An equimolar amount (0.1 mmol) of each component were added to a screw-capped vial and 3 mL of ethanol added to effect a clear colorless solution that was allowed to slowly concentrate over two weeks. A homogeneous mass of crystals was obtained.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. All hydrogen atoms were located in Fourier-difference maps. Hydrogen atoms involved in hydrogen-bonding interactions were restrained in the refinement with N-H = 0.87 (2) Å and with U iso (H) = 1.2U eq (N). The aromatic H atoms were included in the refinement at calculated positions with C-H = 0.95 Å and U iso (H) = 1.2U eq (C).  Computer programs: SMART and SAINT (Bruker, 2014), SHELXT2018/2 (Sheldrick, 2015a), SHELXL2018/3 (Sheldrick, 2015b) and X-SEED (Barbour, 2001).

2-Amino-6-bromopyridinium 2,3,5,6-tetrafluorobenzoate
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.