Crystallographic and spectroscopic characterization of 4-nitro-2-(trifluoromethyl)benzoic acid and 4-nitro-3-(trifluoromethyl)benzoic acid

The title compounds, two isomers of nitro trifluoromethyl benzoic acid, each contain a nitro functionality para to the carboxylic acid group, with the trifluoromethyl substituent ortho to the acid group in the 2-isomer and ortho to the nitro group in the 3-isomer. The regiochemistry with respect to the trifluoromethyl group results in steric interactions that rotate the carboxylic acid group or the nitro group out of the aromatic plane in the 2- and 3-isomer, respectively.


Chemical context
The title compounds, 4-nitro-2-(trifluoromethyl)benzoic acid (I) and 4-nitro-3-(trifluoromethyl)benzoic acid (II), are trisubstituted aromatic compounds featuring a carboxylic acid, a nitro group and a trifluoromethyl group. Although all ten isomers of nitro trifluoromethyl benzoic acid are available commercially, none of their crystal structures have been reported. 4-Nitro-2-(trifluoromethyl)benzoic acid (I) may be synthesized from 2-(trifluoromethyl)benzoic acid by treating it with concentrated sulfuric acid, stirring, and adding fuming nitric acid dropwise (Kompella et al., 2017). 4-Nitro-2-(trifluoromethyl)benzoic acid (I) has been used in the syntheses of potential pharmaceuticals, for example in anti-tumor pyridinone (Cheung et al., 2017) and urea derivatives (Nishio et al., 2017). 4-Nitro-3-(trifluoromethyl)benzoic acid (II) was first reported in 1951 after being prepared from the corresponding nitrile (Caldwell & Sayin, 1951). The compound has recently been used for the synthesis of glutamate receptor antagonists (Selvam et al., 2018) that have potential as therapies for diseases such as Parkinson's.
A notable difference in the molecular structures of the title compounds is the influence of the trifluoromethyl substituent on the co-planarity of the carboxylic acid and nitro groups with the aromatic ring plane (Fig. 3). In 4-nitro-2-(trifluoromethyl)benzoic acid (I), the trifluoromethyl group ortho to the carboxylic acid moiety rotates it out of the plane of the aromatic ring, with a plane-to-plane angle of 47.2 (1) , whereas the nitro group is almost co-planar with the aromatic ring, with an angle of 2.0 (1) . Conversely, in 4-nitro-3-(trifluoromethyl)benzoic acid (II), the trifluoromethyl group ortho to the nitro moiety rotates it out of the plane of the aromatic ring, with a plane-to-plane angle of 51.3 (1) , whereas the carboxylic acid group is closer to co-planar with the aromatic ring, with an angle of 4.9 (2) .

Supramolecular features
The molecules of the title compounds pack together in the solid state with hydrogen bonding between the carboxylic acid hydrogen atom and the carbonyl oxygen atom of the symmetry-related carboxyl group in a neighboring molecule, forming a dimer with graph-set notation R 2 2 (8). This centrosymmetric pairwise hydrogen-bonding dimer formation results in short hydrogen-bonding distances of 2.7042 (14) Å in (I) (Fig. 4, Table 1) and 2.6337 (16) in (II) (Fig. 5, Table 2).

Figure 1
A view of 4-nitro-2-(trifluoromethyl)benzoic acid (I) with the atomnumbering scheme. Displacement ellipsoids are shown at the 50% probability level.
3.907 (1) Å , a centroid-to-plane distance of 3.820 (1) Å , and a ring-offset slippage of 0.822 (2) Å . An intermolecular fluorine-fluorine interaction is also observed with a length of 2.927 (1) Å that is similar to the sum of the van der Waals radii (2.94 Å ; Bondi, 1964). The hydrogen bonded dimers of 4-nitro-3-(trifluoromethyl)benzoic acid (II) pack together in a similar way, but with a longer fluorine-fluorine contact [2.975 (2) Å ] and a highly offset face-to-face geometric arrangement of the aromatic rings characterized by a large ring-offset slippage of 1.733 (2) Å such that the aromatic rings are barely overlapped (Fig. 7).

Database survey
The Cambridge Structural Database (Groom et al., 2016) contains no isomers of nitro trifluoromethyl benzoic acid. A related derivative of 4-nitro-3-(trifluoromethyl)benzoic acid (II) is 3-methyl-4-nitrobenzoic acid (TOYGIZ), which exhibits a similar hydrogen-bonding motif and hydrogen-bonding distance of 2.617 Å (Saha et al., 2015). As with (II), the methyl group ortho to the nitro moiety in TOYGIZ rotates it out of the plane of the aromatic ring whereas the carboxylic acid group is closer to co-planar with the aromatic ring.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. All non-hydrogen atoms were refined anisotropically. Hydrogen atoms on carbon were included in calculated positions and refined using a riding model with C-H = 0.95 and U iso (H) = 1.2U eq (C) of the aryl Catoms the hydrogens are riding on. The positions of the carboxylic acid hydrogen atoms were found in the difference map and the atoms refined semi-freely using a distance restraint d(O-H) = 0.84 Å , and U iso (H) = 1.2U eq (O). 4-Nitro-3-(trifluoromethyl)benzoic acid (II) was found to be multiply non-merohedrally twinned. Recrystallization attempts did not yield untwinned crystals. Three components were integrated with SAINT using the multiple-component orientation matrix produced by CELL_NOW (Sheldrick, 2003), and the data were absorption corrected and scaled with TWINABS (Sheldrick, 2008a). The initial solution was found and refined with merged and roughly detwinned HKLF 4 format data before final refinement against HKLF5 format data constructed from all observations involving domain 1 only. The twin ratio (SHELXL BASF parameters) refined to 0.0961 (3) and 0.0326 (2).

Funding information
This work was supported by Vassar College. X-ray facilities were provided by the US National Science Foundation (Grants Nos. 0521237 and 0911324 to JMT). We acknowledge the Salmon Fund of Vassar College for funding publication expenses.

4-Nitro-2-(trifluoromethyl)benzoic acid (I)
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.