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.

Abstract

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 R ⁴ ₄ (12). Hydrogen-bonding distances of 2.5219 (11) and 2.8213 (11) Å are observed between the donor carb­oxy­lic acid and the bridging water acceptor, and the donor water and carbonyl oxygen acceptor, respectively. 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 with distances of 3.1769 (11) and 2.8455 (11) Å, respectively. 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 (Li et al., 2019 ▸). 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 ▸).

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)°.

Figure 1.

A view of 5-(tri­fluoro­meth­yl)picolinic acid (I) hydrate with the atom-numbering scheme. Displacement ellipsoids are shown at the 50% probability level.

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 ▸).

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯O1W	0.92 (2)	1.60 (2)	2.5219 (11)	174 (2)
O1W—H2W⋯O2i	0.808 (19)	2.038 (19)	2.8213 (11)	163.2 (17)
O1W—H1W⋯O2ii	0.859 (19)	2.615 (18)	3.1769 (11)	124.1 (13)
O1W—H1W⋯Nii	0.859 (19)	2.008 (18)	2.8455 (11)	164.5 (16)

Symmetry codes: (i) ; (ii) .

The mol­ecular packing in the solid state can be characterized by the 5-(tri­fluoro­meth­yl)picolinic acid (I) hydrate asymmetric unit first forming a centrosymmetric water-bridged dimer unit with graph-set notation (12) (Fig. 2 ▸). The carb­oxy­lic acid hydrogen atom and the water oxygen form the stronger hydrogen bond, with an O1⋯O1W distance of 2.5219 (11) Å characterizing the O1—H1⋯O1W hydrogen bond, while the water hydrogen atom H2W bonds to the carbonyl oxygen atom with an O1W⋯O2ⁱ distance of 2.8213 (11) Å charaterizing the O1W-–H2W⋯O2ⁱ hydrogen bond [symmetry code: (i) −x + 1, −y + 1, −z + 2].

Figure 2.

A view of the inter­molecular water-bridged hydrogen-bonding dimer in 5-(tri­fluoro­meth­yl)picolinic acid (I) hydrate.

The water mol­ecules, specifically using the other water hydrogen atom H1W, further bridge the dimer units together to form a pleated strip or tape motif that propagates along the crystallographic [010] direction (Fig. 3 ▸). The the O1W⋯Nⁱⁱ and O1W⋯O2ⁱⁱ distances of 3.1769 (11) and 2.8455 (11) Å, respectively, characterize the O1W—H1W⋯Nⁱⁱ and O1W—H1W⋯O2ⁱⁱ hydrogen bonds [symmetry code: (ii) −x + 1, y − , −z + ]. The pleated nature of the strip exposes the H1W hydrogen atom of every other dimer to a pyridine nitro­gen in the strip adjacent to it, forming a thick two-dimensional sheet (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 ▸).

Figure 3.

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

Figure 4.

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.

The sheets stack in the [100] direction (Fig. 6 ▸). The forces that guide the inter­molecular inter­actions between neighboring sheets are van der Waals forces including F⋯F and C—H⋯F contacts. The shortest weak C_ar­yl—H⋯F inter­action, C4—H4A⋯F2 exhibits an H⋯F distance of 2.495 (1) Å. The most notable inter­action is a dimeric F⋯F inter­action between CF₃ groups on neighboring sheets with an F1⋯F3 distance of 3.077 (1) Å, which is ∼0.15 Å longer than the sum of the van der Waals radii of fluorine (Bondi, 1964 ▸).

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.

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—H⋯N and O—H⋯O 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 H₂O₂ hydrogen atoms and two carboxyl­ate groups, and an N—H⋯O hydrogen bond between the protonated pyridine nitro­gen atom and one oxygen atom of the H₂O₂ mol­ecule.

5-(Tri­fluoro­meth­yl)-2-pyridine­carb­oxy­lic acid has been used as a monoanionic ligand in several metal complexes, including with Co^II (VOVZOY; Li et al., 2019 ▸), Cr^III (QEGWOR; Chai et al., 2017 ▸), Mn^II (ROKSIW; Wang et al., 2019 ▸), and Ir^III [COKGAN and COKGIV (Sanner et al., 2019 ▸); 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(H₂O)₂]NO₃·H₂O hydrogen bonds into thick two-dimensional sheets with the tri­fluoro­methyl­aromatic groups extending to the faces of the sheets (Chai et al., 2017 ▸).

Synthesis and crystallization  

5-(Tri­fluoro­meth­yl)-2-pyridine­carb­oxy­lic acid (I, 95%) was purchased from Aldrich Chemical Company, USA, and was used as received.

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.

Table 2. Experimental details.

Crystal data
Chemical formula	C7H4F3NO2·H2O
M r	209.13
Crystal system, space group	Monoclinic, P21/c
Temperature (K)	125
a, b, c (Å)	8.9213 (10), 10.0759 (12), 9.1010 (11)
β (°)	99.983 (2)
V (Å3)	805.70 (16)
Z	4
Radiation type	Mo Kα
μ (mm−1)	0.18
Crystal size (mm)	0.32 × 0.25 × 0.14
Data collection
Diffractometer	Bruker APEXII CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2017 ▸)
T min, T max	0.89, 0.98
No. of measured, independent and observed [I > 2σ(I)] reflections	19282, 2463, 2126
R int	0.026
(sin θ/λ)max (Å−1)	0.715
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.034, 0.103, 1.07
No. of reflections	2463
No. of parameters	139
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.50, −0.26

Computer programs: APEX2 and SAINT (Bruker, 2017 ▸), SHELXT2014/5 (Sheldrick, 2015a ▸), SHELXL2017/1 (Sheldrick, 2015b ▸), SHELXTL2014 (Sheldrick, 2008 ▸), OLEX2 (Dolomanov et al., 2009 ▸), and Mercury (Macrae et al., 2020 ▸).

Analytical data  

¹H NMR (Bruker Avance III HD 400 MHz, DMSO d ₆): δ 3.70 (br s, OH), 8.21 (d, 1H, C_ar­yl H, J_ortho = 8.0 Hz), 8.37 (dd, 1H, C_ar­yl H, J_ortho = 8.2 Hz, J_meta = 2.0 Hz), 9.07 (s, 1H, C_ar­yl H). ¹³C NMR (¹³C{¹H}, 100.6 MHz, DMSO d ₆): δ 123.23 (q, CF₃, J _C–F = 272.8 Hz), 124.73 (s, C _ar­yl H), 127.30 (q, C _ar­ylCF₃, J _C–F = 32.7 Hz), 135.12 (q, C _ar­ylH, J _C–F = 3.5 Hz), 146.24 (q, C _ar­ylH, J _C–F = 3.8 Hz), 151.98 (s, C _ar­ylCOOH), 165.13 (s, COOH). ¹⁹F NMR (¹⁹F{¹H}, 376.5 MHz, DMSO d₆): δ −61.35 (s, 3F, CF3). IR (Thermo Nicolet iS50, FT–IR, KBr pellet, cm⁻¹): 3469 (s br, O—H str), 3050 (s, C_ar­yl—H str), 2849 (w), 2571 (w), 1961 (m), 1707 (s, C=O str), 1606 (s), 1582 (s), 1493 (s), 1440 (s), 1392 (s), 1328 (m), 1290 (m), 1251 (s), 1163 (m), 1126 (s), 1075 (s), 1023 (s), 948 (s), 878 (m), 864 (s), 806 (s), 760 (s), 704 (s), 643 (s), 524 (s). GC–MS (Agilent Technologies 7890A GC/5975C MS): M⁺ = 191 amu, corresponding to the anhydrous form, 5-(tri­fluoro­meth­yl)pyridine-2-carb­oxy­lic acid (I), whose calculated exact mol­ecular ion mass is 191.02 amu.

Supplementary Material

CCDC reference: 2036131

Additional supporting information: crystallographic information; 3D view; checkCIF report

supplementary crystallographic information

Crystal data

C7H4F3NO2·H2O	F(000) = 424
Mr = 209.13	Dx = 1.724 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 8.9213 (10) Å	Cell parameters from 7786 reflections
b = 10.0759 (12) Å	θ = 3.0–30.2°
c = 9.1010 (11) Å	µ = 0.18 mm−1
β = 99.983 (2)°	T = 125 K
V = 805.70 (16) Å3	Block, colourless
Z = 4	0.32 × 0.25 × 0.14 mm

Data collection

Bruker APEXII CCD diffractometer	2463 independent reflections
Radiation source: fine-focus sealed tube	2126 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.026
Detector resolution: 8.3333 pixels mm-1	θmax = 30.5°, θmin = 2.3°
φ and ω scans	h = −12→12
Absorption correction: multi-scan (SADABS; Bruker, 2017)	k = −14→14
Tmin = 0.89, Tmax = 0.98	l = −13→13
19282 measured reflections

Refinement

Refinement on F2	Primary atom site location: dual
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.034	Hydrogen site location: mixed
wR(F2) = 0.103	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ2(Fo2) + (0.0559P)2 + 0.2301P] where P = (Fo2 + 2Fc2)/3
2463 reflections	(Δ/σ)max < 0.001
139 parameters	Δρmax = 0.50 e Å−3
0 restraints	Δρmin = −0.26 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
F1	1.02797 (8)	0.44945 (10)	0.19056 (8)	0.0387 (2)
F2	0.91945 (11)	0.63911 (8)	0.13936 (9)	0.0398 (2)
F3	0.80545 (8)	0.45876 (7)	0.06062 (7)	0.02763 (17)
O1	0.62864 (9)	0.36976 (7)	0.76271 (8)	0.02126 (17)
H1	0.572 (2)	0.365 (2)	0.838 (2)	0.056 (6)*
O2	0.57174 (9)	0.58725 (7)	0.74769 (8)	0.02259 (17)
N	0.69746 (10)	0.60686 (8)	0.49521 (9)	0.01815 (18)
C1	0.62637 (11)	0.48809 (9)	0.70248 (10)	0.01643 (18)
C2	0.70005 (11)	0.48977 (9)	0.56536 (10)	0.01547 (18)
C3	0.76396 (12)	0.37599 (9)	0.51689 (11)	0.01936 (19)
H3A	0.762813	0.29467	0.569519	0.023*
C4	0.82968 (12)	0.38369 (10)	0.38964 (11)	0.0205 (2)
H4A	0.87462	0.307748	0.353174	0.025*
C5	0.82825 (11)	0.50451 (10)	0.31708 (11)	0.01741 (19)
C6	0.76044 (12)	0.61375 (10)	0.37220 (11)	0.01917 (19)
H6A	0.758767	0.695976	0.32085	0.023*
C7	0.89493 (12)	0.51403 (10)	0.17683 (11)	0.0210 (2)
O1W	0.46520 (10)	0.34230 (8)	0.96069 (9)	0.02433 (18)
H2W	0.469 (2)	0.3734 (17)	1.043 (2)	0.040 (5)*
H1W	0.4241 (19)	0.2651 (19)	0.9607 (19)	0.043 (5)*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
F1	0.0238 (4)	0.0669 (6)	0.0280 (4)	0.0091 (3)	0.0118 (3)	−0.0011 (4)
F2	0.0630 (5)	0.0278 (4)	0.0368 (4)	−0.0179 (3)	0.0317 (4)	−0.0058 (3)
F3	0.0315 (4)	0.0352 (4)	0.0167 (3)	−0.0061 (3)	0.0055 (2)	−0.0055 (3)
O1	0.0303 (4)	0.0167 (3)	0.0190 (3)	0.0011 (3)	0.0104 (3)	0.0034 (3)
O2	0.0328 (4)	0.0185 (3)	0.0189 (3)	0.0026 (3)	0.0112 (3)	−0.0006 (3)
N	0.0240 (4)	0.0154 (4)	0.0161 (4)	0.0013 (3)	0.0066 (3)	0.0005 (3)
C1	0.0192 (4)	0.0165 (4)	0.0135 (4)	−0.0014 (3)	0.0027 (3)	0.0004 (3)
C2	0.0180 (4)	0.0150 (4)	0.0136 (4)	−0.0004 (3)	0.0031 (3)	−0.0006 (3)
C3	0.0252 (5)	0.0151 (4)	0.0188 (4)	0.0012 (3)	0.0066 (4)	0.0006 (3)
C4	0.0248 (5)	0.0174 (4)	0.0207 (4)	0.0015 (3)	0.0078 (4)	−0.0033 (3)
C5	0.0182 (4)	0.0197 (4)	0.0153 (4)	−0.0028 (3)	0.0056 (3)	−0.0031 (3)
C6	0.0252 (5)	0.0167 (4)	0.0168 (4)	−0.0006 (3)	0.0070 (3)	0.0006 (3)
C7	0.0218 (5)	0.0234 (5)	0.0194 (4)	−0.0044 (4)	0.0079 (4)	−0.0036 (4)
O1W	0.0376 (4)	0.0188 (3)	0.0198 (4)	−0.0073 (3)	0.0140 (3)	−0.0031 (3)

Geometric parameters (Å, º)

F1—C7	1.3402 (13)	C3—C4	1.3879 (13)
F2—C7	1.3335 (13)	C3—H3A	0.95
F3—C7	1.3317 (12)	C4—C5	1.3840 (14)
O1—C1	1.3109 (11)	C4—H4A	0.95
O1—H1	0.92 (2)	C5—C6	1.3908 (13)
O2—C1	1.2143 (12)	C5—C7	1.5019 (13)
N—C6	1.3387 (12)	C6—H6A	0.95
N—C2	1.3397 (12)	O1W—H2W	0.808 (19)
C1—C2	1.5081 (13)	O1W—H1W	0.859 (19)
C2—C3	1.3861 (13)
C1—O1—H1	113.0 (13)	C4—C5—C6	119.52 (9)
C6—N—C2	117.98 (8)	C4—C5—C7	119.30 (9)
O2—C1—O1	125.78 (9)	C6—C5—C7	121.14 (9)
O2—C1—C2	121.95 (8)	N—C6—C5	122.17 (9)
O1—C1—C2	112.26 (8)	N—C6—H6A	118.9
N—C2—C3	123.42 (9)	C5—C6—H6A	118.9
N—C2—C1	115.48 (8)	F3—C7—F2	107.12 (9)
C3—C2—C1	121.09 (8)	F3—C7—F1	105.68 (8)
C2—C3—C4	118.41 (9)	F2—C7—F1	107.51 (9)
C2—C3—H3A	120.8	F3—C7—C5	112.15 (8)
C4—C3—H3A	120.8	F2—C7—C5	112.61 (8)
C5—C4—C3	118.49 (9)	F1—C7—C5	111.38 (9)
C5—C4—H4A	120.8	H2W—O1W—H1W	107.4 (16)
C3—C4—H4A	120.8

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O1W	0.92 (2)	1.60 (2)	2.5219 (11)	174 (2)
O1W—H2W···O2i	0.808 (19)	2.038 (19)	2.8213 (11)	163.2 (17)
O1W—H1W···O2ii	0.859 (19)	2.615 (18)	3.1769 (11)	124.1 (13)
O1W—H1W···Nii	0.859 (19)	2.008 (18)	2.8455 (11)	164.5 (16)

Symmetry codes: (i) −x+1, −y+1, −z+2; (ii) −x+1, y−1/2, −z+3/2.

Funding Statement

This work was funded by Vassar College grant . National Science Foundation grants 0521237 and 0911324. Salmon Fund and Olin College Fund of Vassar College grant .