The crystal structure of 5-(trifluoromethyl)picolinic acid monohydrate reveals a water-bridged hydrogen-bonding network

The title compound, [systematic name: 5-(trifluoromethyl)pyridine-2-carboxylic acid monohydrate], C7H4F3NO2·H2O, is the acid hydrate of a pyridine with a carboxylic acid group and a trifluoromethyl substituent situated para to one another on the aromatic ring. The molecule forms a centrosymmetric water-bridged hydrogen-bonding dimer with graph-set notation (12). The dimers are further linked into a two-dimensional sheet via two longer intermolecular hydrogen-bonding interactions between the second hydrogen atom on the bridging water molecule and both a pyridine nitrogen atom and carbonyl oxygen. The trifluoromethyl groups extend out the faces of the sheet providing for F⋯F and C—H⋯F contacts between the sheets, completing the three-dimensional packing.


Chemical context
Picolinic acids, pyridine derivatives with a carboxylic acid substituent at the 2-position, are common bidentate chelating agents of metallic elements in the human body (Grant et al., 2009). The title compound, the hydrate of 5-(trifluoromethyl)-2-pyridinecarboxylic acid (I), commonly known as 5-(trifluoromethyl)picolinic acid, is a derivative of picolinic acid with potent chelating abilities and biological activities . Its transition-metal complexes also exhibit outstanding photophysical and electrochemical properties that make them promising phosphorescent materials for OLEDs (Wei et al., 2016). The compound may be synthesized from a range of synthetic routes, one of which relies on the carboxylation reaction of 2-bromo-5-(trifluoromethyl)pyridine with butyllithium (Cottet et al., 2003). ISSN 2056-9890

Structural commentary
The structure of 5-(trifluoromethyl)picolinic acid (I) reveals that the crystalline material obtained from the supplier is a hydrate and confirms the position of the carboxylic acid group ortho to the pyridine nitrogen atom with trifluoromethyl substituent situated para to the acid group on the aromatic ring ( Fig. 1). The two aromatic carbon-nitrogen bonds have bond lengths of N-C2 of 1.3397 (12) Å and N-C6 of 1.3387 (12) Å , shorter than the aromatic C-C bonds, which have an average bond length of 1.387 (3) Å , a wedge-type motif typical in pyridine structures (Montgomery et al., 2015). The aromatic carboxylic acid substituent has a C1-C2 bond length of 1.5081 (13) Å , similar to that of the trifluoromethyl substituent C5-C7 of 1.5019 (13) Å , and the C-F bond lengths of the trifluoromethyl group have an average bond length of 1.335 (4) Å . The carboxylic acid group is co-planar with the aromatic pyridine ring, with least-squares planes at an angle of 1.8 (2) .

Supramolecular features
The structure of 5-(trifluoromethyl)picolinic acid (I) reported is a hydrate (Fig. 1) exhibiting a water-linked two-dimensional hydrogen-bonding network. Four different hydrogen-bonding interactions are observed between the picolinic acid and water molecule, which acts as both a hydrogen-bonding donor and acceptor with the carboxylic acid group and pyridine nitrogen atom (Table 1).

Figure 3
A view of a pleated strip formed between the water-bridged hydrogenbonding dimers in 5-(trifluoromethyl)picolinic acid (I) hydrate.

Figure 1
A view of 5-(trifluoromethyl)picolinic acid (I) hydrate with the atomnumbering scheme. Displacement ellipsoids are shown at the 50% probability level.
( Fig. 4). The sheet can be considered a bilayer with a hydrophilic core due to the presence of water molecules and strong hydrogen bonding in the center and the more hydrophobic trifluoromethylaromatic groups extending to the faces of the sheet (Fig. 5).

Database survey
Monocarboxylic derivatives of pyridine, pyridinecarboxylic acids, are also commonly known as picolinic acid, nicotinic acid, or isonicotinic acid when the carboxyl group resides at the 2-, 3-, or 4-position, respectively. The Cambridge Structural Database (Version 5.40, update of March 2020; Groom et al., 2016) contains no isomers of trifluoromethyl-substituted pyridinecarboxylic acids. The crystal structure of the base of the title compound, picolinic acid (PICOLA02), was shown to be 1:1 co-crystals of its neutral and zwitterionic forms, where the nitrogen atom can both be protonated and deprotonated (Hamazaki et al., 1998). The interactions form a zigzag chain by N-HÁ Á ÁN and O-HÁ Á ÁO intermolecular hydrogen bonding. A zwitterionic hydrogen-bonding motif can be found in substituted picolinic acid derivatives as well, such as 3-thioxo-2-pyridinecarboxylic acid (MPYDCX01; Bourne & Taylor, 1983).
A related solvated picolinic acid crystal structure can be found in the crystal structure of picolinic acid peroxosolvate (ANINES) which, while zwitterionic, exhibits a solvate-linked hydrogen-bonding pattern (Medvedev et al., 2013). In this structure, every hydrogen peroxide molecule links three picolinic acid molecules together with two hydrogen bonds between the H 2 O 2 hydrogen atoms and two carboxylate groups, and an N-HÁ Á ÁO hydrogen bond between the protonated pyridine nitrogen atom and one oxygen atom of the H 2 O 2 molecule. 5-(Trifluoromethyl)-2-pyridinecarboxylic acid has been used as a monoanionic ligand in several metal complexes, including with Co II ( A view of the sheet hydrogen-bonding network in 5-(trifluoromethyl)picolinic acid (I) hydrate viewing the water-bridge hydrogen-bonding dimers end-on shows the hydrogen-bonding interactions between the pleated strips forming a two-dimensional sheet.

Figure 5
An edge-on view of the two-dimensional sheet formed between the water-bridged hydrogen-bonding dimers in 5-(trifluoromethyl)picolinic acid (I) hydrate.

Figure 6
A view of the stacking of the two-dimensional sheets in 5-(trifluoromethyl)picolinic acid (I) hydrate showing the trifluoromethylaromatic interactions at the interfaces of the sheets.
GIZJOR (Hao et al., 2019)]. While the Co II and Mn II complexes engage in intermolecular hydrogen bonding with metal-coordinated water molecules, the Cr III complex contains a water of solvation that facilitates the formation of a hydrogen-bonding network. In a fashion reminiscent of 5-(trifluoromethyl)picolinic acid (I) hydrate itself, [Cr(5-(trifluoromethyl)picolinate) 2 (H 2 O) 2 ]NO 3 ÁH 2 O hydrogen bonds into thick two-dimensional sheets with the trifluoromethylaromatic groups extending to the faces of the sheets (Chai et al., 2017).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. All non-hydrogen atoms were refined anisotropically. Hydrogen atoms on carbon atoms were included in calculated positions and refined using a riding model with C-H = 0.95 Å and U iso (H) = 1.2U eq (C) of the aryl C-atoms. The position of the carboxylic acid and water hydrogen atoms were found in the difference map and refined freely.

Funding information
This work was supported by Vassar College. X-ray facilities were provided by the US National Science Foundation (grant Nos. 0521237 and 0911324 to JMT). We acknowledge the Salmon Fund and Olin College Fund of Vassar College for funding publication expenses. The crystal structure of 5-(trifluoromethyl)picolinic acid monohydrate reveals a water-bridged hydrogen-bonding network Naike Ye and Joseph M. Tanski

5-(Trifluoromethyl)pyridine-2-carboxylic acid monohydrate
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.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 ) x y z U iso */U eq F1