2-Fluoro-4-(meth­oxy­carbon­yl)benzoic acid

Wagner, C.E.; Groy, T.L.

doi:10.1107/S1600536810032253

organic compounds

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ISSN: 2056-9890

Volume 66| Part 9| September 2010| Page o2340

https://doi.org/10.1107/S1600536810032253

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2-Fluoro-4-(methoxycarbonyl)benzoic acid

Carl E. Wagner ^a ^* and Thomas L. Groy ^b

^aDivision of Mathematics and Natural Sciences, Arizona State University, West Campus, Glendale, AZ 85306, USA, and ^bDepartment of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287-1604, USA
^*Correspondence e-mail: carl.wagner@asu.edu

(Received 4 July 2010; accepted 11 August 2010; online 18 August 2010)

In the crystal of the title compound, C₉H₇FO₄, classical carboxylate inversion dimers are linked by pairs of O—H⋯O hydrogen bonds. The packing is consolidated by C—H⋯F and C—H⋯O interactions. The benzene ring and the methoxycarbonyl group are nearly coplanar, with a dihedral angle of 1.5 (3)° between them, whereas the carboxyl group has a dihedral angle of 20.2 (4)° with respect to the benzene ring.

Related literature

For background to the applications of the title compound, see: Jiang et al. (2008 ); Sakaki et al. (2007 ). For related structures, see: Wagner et al. (2009 ).

Experimental

Crystal data

C₉H₇FO₄
M_r = 198.15
Triclinic, $[P \overline 1]$
a = 7.536 (7) Å
b = 7.591 (7) Å
c = 8.523 (8) Å
α = 99.480 (14)°
β = 108.748 (13)°
γ = 99.240 (14)°
V = 443.3 (7) Å³
Z = 2
Mo Kα radiation
μ = 0.13 mm⁻¹
T = 296 K
0.25 × 0.19 × 0.08 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ) T_min = 0.969, T_max = 0.990
2526 measured reflections
1535 independent reflections
1025 reflections with I > 2σ(I)
R_int = 0.025

Refinement

R[F² > 2σ(F²)] = 0.066
wR(F²) = 0.190
S = 1.02
1535 reflections
128 parameters
H-atom parameters constrained
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C9—H9A⋯F1ⁱ	0.96	2.54	3.278 (5)	134 (1)
O2ⁱⁱ—H2Aⁱⁱ⋯O1	0.82	1.86	2.672 (4)	170 (1)
C3—H3A⋯O3ⁱⁱⁱ	0.93	2.53	3.325 (4)	144 (1)
Symmetry codes: (i) x-1, y-1, z-1; (ii) -x+2, -y+3, -z+1; (iii) -x, -y+2, -z+1.

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT-Plus (Bruker, 2008); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XSHELL (Bruker, 2004 ); software used to prepare material for publication: APEX2.

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536810032253/pb2036sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810032253/pb2036Isup2.hkl

checkCIF report

Comment top

The title compound, 4-(methoxycarbonyl)-2-fluorobenzoic acid, has recently been used to prepare novel diazepinylbenzoic acid retinoid-X-receptor antagonists (Jiang et al., 2008; Sakaki et al., 2007) as potential oral anti-obesity and anti-diabetic treatments as well as novel retinoid-X-receptor agonists with potential to treat various human cancers. Thus, the X-ray diffraction data of the present study confirms the fluorine locus for 4-(methoxycarbonyl)-2-fluorobenzoic acid.

The structure consists of sheets parallel to (212) stabilized by six intermolecular hydrogen interactions per molecule as shown in Table 1. The benzene ring and the methoxycarbonyl group are essentially coplanar as shown by the 1.51 (25)° dihedral angle between the two planes. However, the carboxylic acid is not coplanar with the benzene ring, as shown by the 20.18 (36)° dihedral angle between those two planes.

Related literature top

For background to the applications of the title compound, see: Jiang et al. (2008); Sakaki et al. (2007). For related structures, see: Wagner et al. (2009).

Experimental top

The method of Sakaki and co-workers (Sakaki et al., 2007) was followed to synthesize (1). To a flask containing 3-fluoro-4-formylmethylbenzoate (Wagner et al., 2009) (9.22 g, 50.5 mmol) and sulfamic acid (5.40 g, 55.6 mmol) in water (21 ml) and ACN (42 ml) was slowly added a solution of 80% NaClO₂ (4.92 g, 53.8 mmol) in water (21 ml) at room temperature. After being stirred for 1 h, the reaction solution was added to a saturated, aqueous solution of Na₂SO₃ (75 ml) and 1 N HCl (150 ml), and the resulting solution was extracted with ethyl acetate (75 ml) three times. The combined organic extracts were washed with brine, dried over sodium sulfate, and the solvents were removed in vacuo to give crude (1) (7.56 g, 75%) as a white solid. A small sample was crystallized from hot ethyl acetate to give pure (1) as white crystals, m.p. 154–155 °C: ¹H NMR (400 MHz, CDCl₃) δ 10.5 (br s, 1H), 8.10 (t, J = 7.8, 1H), 7.89 (d, J = 8.2, 1H), 7.82 (d, J = 11.0, 1H), 3.97 (s, 3H); ¹³C NMR (100.6 MHz, CDCl₃) δ 168.6, 168.5, 165.0, 164.9, 163.4, 160.8, 136.7, 136.6, 132.8, 124.9, 124.8, 121.3, 121.2, 118,4, 118.1, 52.8; LC-APCI-MS (M+) calcd for C₉H₇O₄F 198.0328, found 198.0331.

Structure description top

For background to the applications of the title compound, see: Jiang et al. (2008); Sakaki et al. (2007). For related structures, see: Wagner et al. (2009).

Computing details top

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT-Plus (Bruker, 2008); data reduction: SAINT-Plus (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XSHELL (Bruker, 2004); software used to prepare material for publication: APEX2 (Bruker, 2008).

Figures top

	Fig. 1. Labeled thermal ellipsoid plot of (1) shown at the 50% probability level for all non-H atoms.
	Fig. 2. Molecular pair of (1) shown at the 50% probability level for all non-H atoms illustrating classical intermolecular centrosymmetric carboxylic acid hydrogen bonding interactions.
	Fig. 3. Packing diagram of (1) shown at the 50% probability level for all non-H atoms showing the alternating molecular orientations in two adjacent layers.

2-Fluoro-4-(methoxycarbonyl)benzoic acid top

Crystal data top

C₉H₇FO₄	Z = 2
M_r = 198.15	F(000) = 204
Triclinic, P1	D_x = 1.484 Mg m⁻³
Hall symbol: -P 1	Melting point: 427 K
a = 7.536 (7) Å	Mo Kα radiation, λ = 0.71073 Å
b = 7.591 (7) Å	Cell parameters from 51 reflections
c = 8.523 (8) Å	θ = 4.5–11.9°
α = 99.480 (14)°	µ = 0.13 mm⁻¹
β = 108.748 (13)°	T = 296 K
γ = 99.240 (14)°	Plate, colourless
V = 443.3 (7) Å³	0.25 × 0.19 × 0.08 mm

Data collection top

Bruker SMART APEX CCD diffractometer	1535 independent reflections
Radiation source: sealed tube	1025 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.025
ω and φ scans	θ_max = 25.0°, θ_min = 2.6°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −8→8
T_min = 0.969, T_max = 0.990	k = −9→8
2526 measured reflections	l = −10→10

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.066	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.190	H-atom parameters constrained
S = 1.02	w = 1/[σ²(F_o²) + (0.P)² + 0.1145P] where P = (F_o² + 2F_c²)/3
1535 reflections	(Δ/σ)_max = 0.001
128 parameters	Δρ_max = 0.24 e Å⁻³
0 restraints	Δρ_min = −0.22 e Å⁻³

Crystal data top

C₉H₇FO₄	γ = 99.240 (14)°
M_r = 198.15	V = 443.3 (7) Å³
Triclinic, P1	Z = 2
a = 7.536 (7) Å	Mo Kα radiation
b = 7.591 (7) Å	µ = 0.13 mm⁻¹
c = 8.523 (8) Å	T = 296 K
α = 99.480 (14)°	0.25 × 0.19 × 0.08 mm
β = 108.748 (13)°

Data collection top

Bruker SMART APEX CCD diffractometer	1535 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2008)	1025 reflections with I > 2σ(I)
T_min = 0.969, T_max = 0.990	R_int = 0.025
2526 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.066	0 restraints
wR(F²) = 0.190	H-atom parameters constrained
S = 1.02	Δρ_max = 0.24 e Å⁻³
1535 reflections	Δρ_min = −0.22 e Å⁻³
128 parameters

Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

H atoms were placed geometrically and allowed to refine as atoms riding on their bonding partners. The hydrogen was placed on the carboxylic acid based on the longer of the carboxylic acid carbon-oxygen bonds.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
F1	0.4739 (2)	1.3542 (2)	0.6014 (2)	0.0629 (5)
O1	0.8299 (2)	1.4232 (4)	0.5841 (2)	0.0672 (7)
O2	0.8296 (2)	1.3413 (2)	0.3192 (2)	0.0716 (8)
H2A	0.9326	1.4171	0.3603	0.107*
O3	−0.1230 (4)	0.8633 (4)	0.2593 (2)	0.0798 (9)
O4	−0.0485 (2)	0.7256 (2)	0.0437 (2)	0.0582 (7)
C1	0.5568 (4)	1.2070 (4)	0.3734 (2)	0.0453 (7)
C2	0.4248 (4)	1.2212 (4)	0.4562 (2)	0.0464 (7)
C3	0.2443 (4)	1.1083 (4)	0.3967 (2)	0.0479 (8)
H3A	0.1607	1.1227	0.4553	0.057*
C4	0.1871 (4)	0.9720 (4)	0.2478 (2)	0.0437 (7)
C5	0.3166 (4)	0.9507 (4)	0.1625 (2)	0.0495 (8)
H5A	0.2807	0.8584	0.0642	0.059*
C6	0.4976 (5)	1.0670 (4)	0.2248 (4)	0.0527 (8)
H6A	0.5819	1.0523	0.1669	0.063*
C7	0.7527 (4)	1.3333 (4)	0.4321 (4)	0.0503 (8)
C8	−0.0112 (4)	0.8498 (4)	0.1877 (4)	0.0491 (8)
C9	−0.2360 (5)	0.5972 (5)	−0.0216 (4)	0.0692 (10)
H9A	−0.2482	0.5131	−0.1238	0.104*
H9B	−0.3359	0.6639	−0.0462	0.104*
H9C	−0.2474	0.5303	0.0623	0.104*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0579 (11)	0.0628 (13)	0.0540 (10)	−0.0020 (9)	0.0211 (9)	−0.0111 (8)
O1	0.0526 (15)	0.0782 (17)	0.0532 (13)	−0.0072 (11)	0.0119 (10)	0.0038 (11)
O2	0.0590 (16)	0.0765 (18)	0.0690 (15)	−0.0133 (11)	0.0303 (11)	0.0019 (11)
O3	0.0532 (16)	0.088 (2)	0.0828 (17)	−0.0110 (13)	0.0346 (13)	−0.0154 (14)
O4	0.0485 (14)	0.0591 (14)	0.0525 (11)	−0.0015 (10)	0.0137 (10)	−0.0038 (10)
C1	0.0435 (17)	0.0453 (17)	0.0477 (15)	0.0102 (14)	0.0161 (13)	0.0123 (13)
C2	0.0485 (18)	0.0445 (17)	0.0414 (14)	0.0071 (13)	0.0153 (13)	0.0026 (11)
C3	0.0447 (18)	0.051 (2)	0.0470 (15)	0.0086 (14)	0.0202 (13)	0.0045 (13)
C4	0.0431 (17)	0.0430 (16)	0.0434 (15)	0.0074 (13)	0.0149 (13)	0.0091 (11)
C5	0.050 (2)	0.0467 (18)	0.0490 (16)	0.0076 (14)	0.0208 (14)	0.0017 (13)
C6	0.050 (2)	0.056 (2)	0.0535 (17)	0.0099 (15)	0.0243 (14)	0.0063 (14)
C7	0.049 (2)	0.0493 (18)	0.0510 (17)	0.0095 (14)	0.0168 (15)	0.0105 (14)
C8	0.0432 (18)	0.0511 (18)	0.0490 (16)	0.0079 (14)	0.0156 (14)	0.0055 (13)
C9	0.052 (2)	0.062 (2)	0.069 (2)	−0.0055 (17)	0.0060 (16)	−0.0018 (17)

Geometric parameters (Å, º) top

F1—C2	1.364 (3)	C3—C4	1.393 (4)
O1—C7	1.257 (3)	C3—H3A	0.93
O2—C7	1.278 (4)	C4—C5	1.405 (4)
O2—H2A	0.82	C4—C8	1.504 (4)
O3—C8	1.197 (4)	C5—C6	1.384 (4)
O4—C8	1.336 (4)	C5—H5A	0.93
O4—C9	1.460 (4)	C6—H6A	0.93
C1—C2	1.400 (4)	C9—H9A	0.96
C1—C6	1.405 (4)	C9—H9B	0.96
C1—C7	1.504 (4)	C9—H9C	0.96
C2—C3	1.372 (4)

C7—O2—H2A	109.5	C4—C5—H5A	120.0
C8—O4—C9	115.8 (2)	C5—C6—C1	121.4 (3)
C2—C1—C6	116.8 (3)	C5—C6—H6A	119.3
C2—C1—C7	124.1 (3)	C1—C6—H6A	119.3
C6—C1—C7	119.2 (2)	O1—C7—O2	124.2 (3)
F1—C2—C3	117.5 (2)	O1—C7—C1	119.9 (3)
F1—C2—C1	119.5 (3)	O2—C7—C1	115.9 (3)
C3—C2—C1	122.9 (3)	O3—C8—O4	124.0 (3)
C2—C3—C4	119.5 (3)	O3—C8—C4	124.0 (3)
C2—C3—H3A	120.2	O4—C8—C4	112.0 (2)
C4—C3—H3A	120.2	O4—C9—H9A	109.5
C3—C4—C5	119.4 (3)	O4—C9—H9B	109.5
C3—C4—C8	117.9 (2)	H9A—C9—H9B	109.5
C5—C4—C8	122.7 (3)	O4—C9—H9C	109.5
C6—C5—C4	120.0 (3)	H9A—C9—H9C	109.5
C6—C5—H5A	120.0	H9B—C9—H9C	109.5

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C9—H9A···F1ⁱ	0.96	2.54	3.278 (5)	134 (1)
O2ⁱⁱ—H2Aⁱⁱ···O1	0.82	1.86	2.672 (4)	170 (1)
C3—H3A···O3ⁱⁱⁱ	0.93	2.53	3.325 (4)	144 (1)

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

Experimental details

Crystal data
Chemical formula	C₉H₇FO₄
M_r	198.15
Crystal system, space group	Triclinic, P1
Temperature (K)	296
a, b, c (Å)	7.536 (7), 7.591 (7), 8.523 (8)
α, β, γ (°)	99.480 (14), 108.748 (13), 99.240 (14)
V (Å³)	443.3 (7)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.13
Crystal size (mm)	0.25 × 0.19 × 0.08

Data collection
Diffractometer	Bruker SMART APEX CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2008)
T_min, T_max	0.969, 0.990
No. of measured, independent and observed [I > 2σ(I)] reflections	2526, 1535, 1025
R_int	0.025
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.066, 0.190, 1.02
No. of reflections	1535
No. of parameters	128
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.24, −0.22

Computer programs: APEX2 (Bruker, 2008), SAINT-Plus (Bruker, 2008), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), XSHELL (Bruker, 2004).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C9—H9A···F1ⁱ	0.96	2.536	3.278 (5)	134 (1)
O2ⁱⁱ—H2Aⁱⁱ···O1	0.82	1.861	2.672 (4)	170 (1)
C3—H3A···O3ⁱⁱⁱ	0.93	2.525	3.325 (4)	144 (1)

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

Acknowledgements

We thank the Chemistry Division of the National Science Foundation for financial support of this work (Grant CHE-0741978).

References

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