2,6-Difluoro­benzoic acid

Al-Dajani, M.T.M.; Wahab, H.A.; Mohamed, N.; Yeap, C.S.; Fun, H.-K.

doi:10.1107/S1600536810028758

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 66| Part 8| August 2010| Page o2109

https://doi.org/10.1107/S1600536810028758

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2,6-Difluorobenzoic acid

Mohammad T. M. Al-Dajani,^a Habibah A Wahab,^b Nornisah Mohamed,^a Chin Sing Yeap ^c ‡ and Hoong-Kun Fun ^c ^*§

^aSchool of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia, ^bMalaysian Institute of Pharmaceuticals and Nutraceuticals, Ministry of Science, Technology and Innovation, Blok A, 10 Persiaran Bukit Jambul, 11900 Bayan Lepas, Penang, Malaysia, and ^cX-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia
^*Correspondence e-mail: hkfun@usm.my

(Received 17 July 2010; accepted 19 July 2010; online 24 July 2010)

In the title compound, C₇H₄F₂O₂, the dihedral angle between the benzene ring and the carboxylate group is 33.70 (14)°. In the crystal structure, inversion dimers linked by pairs of O—H⋯O hydrogren bonds occur, generating R₂²(8) loops. The dimers are linked into sheets lying parallel to (102) by C—H⋯F hydrogen bonds.

Related literature

For general background to 2,6-diflorobenzylchloride derivatives, see: Beavo (1995 ); Beavo & Reifsnyder (1990 ); Nicholson et al. (1991 ). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 ).

Experimental

Crystal data

C₇H₄F₂O₂
M_r = 158.10
Monoclinic, P 2₁ /c
a = 3.6517 (4) Å
b = 14.1214 (15) Å
c = 12.2850 (13) Å
β = 95.651 (3)°
V = 630.42 (12) Å³
Z = 4
Mo Kα radiation
μ = 0.16 mm⁻¹
T = 100 K
0.73 × 0.19 × 0.09 mm

Data collection

Bruker APEXII DUO CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ) T_min = 0.841, T_max = 0.986
6112 measured reflections
2190 independent reflections
1895 reflections with I > 2σ(I)
R_int = 0.029

Refinement

R[F² > 2σ(F²)] = 0.049
wR(F²) = 0.143
S = 1.12
2190 reflections
116 parameters
All H-atom parameters refined
Δρ_max = 0.47 e Å⁻³
Δρ_min = −0.31 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H1O2⋯O3ⁱ	0.95 (4)	1.68 (4)	2.6318 (14)	174 (4)
C3—H3⋯F2ⁱⁱ	0.98 (2)	2.54 (2)	3.3428 (16)	138.7 (16)
Symmetry codes: (i) -x+1, -y, -z+1; (ii) $[x-1, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]$ .

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536810028758/hb5558sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810028758/hb5558Isup2.hkl

checkCIF report

Comment top

The derivatives of 2,6-diflorobenzylchloride involved in the inhibition of phosphodiesterases (PDEs) are enzymes which catalyze PDEs. These derivatives are classified into seven families, five of which, PDE1–PDE5, have been characterized (Beavo, 1995). The hydrolysis of cyclic nucleotides was evaluated according to the methods in given the references (Beavo & Reifsnyder, 1990; Nicholson et al., 1991).

The molecule of the title compound, (I), (Fig. 1) is not planar with the dihedral angle between the benzene ring and the carboxylate group being 33.70 (14)°. In the crystal structure, the molecules are linked into pairs of centrosymmetric dimers by intermolecular O2—H1O2···O3 hydrogren bonds (Table 1). These dimers are linked into two-dimensional plane by the intermolecular C3—H3A···F2 hydrogen bonds (Fig. 2, Table 1) parallel to (102).

Related literature top

For general background to 2,6-diflorobenzylchloride derivatives, see: Beavo (1995); Beavo & Reifsnyder (1990); Nicholson et al. (1991). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986).

Experimental top

2,6-Difluorobenzylchloride (0.01 mol, 1.7 g) was added drop-wise with stirring into a round bottom flask containing 25 ml water and then refluxed for two and half hours. The gum compound precipitate formed was filtered and dissolved in alkaline water. Hydrochloric acid was then added drop-wise with stirring. The white precipitate formed was dissolved in methanol. Colourless needles of (I) were formed at room temperature overnight and filtrated and dried at 333 K.

Structure description top

For general background to 2,6-diflorobenzylchloride derivatives, see: Beavo (1995); Beavo & Reifsnyder (1990); Nicholson et al. (1991). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986).

Computing details top

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top

	Fig. 1. The molecular structure of (I) with 50% probability ellipsoids for non-H atoms.
	Fig. 2. The crystal packing of (I), viewed down the b axis, showing two 2-D planes.

2,6-Difluorobenzoic acid top

Crystal data top

C₇H₄F₂O₂	F(000) = 320
M_r = 158.10	D_x = 1.666 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 3166 reflections
a = 3.6517 (4) Å	θ = 3.3–32.1°
b = 14.1214 (15) Å	µ = 0.16 mm⁻¹
c = 12.2850 (13) Å	T = 100 K
β = 95.651 (3)°	Needle, colourless
V = 630.42 (12) Å³	0.73 × 0.19 × 0.09 mm
Z = 4

Data collection top

Bruker APEXII DUO CCD diffractometer	2190 independent reflections
Radiation source: fine-focus sealed tube	1895 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.029
φ and ω scans	θ_max = 32.1°, θ_min = 2.2°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −5→5
T_min = 0.841, T_max = 0.986	k = −20→20
6112 measured reflections	l = −18→18

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)] = 0.049	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.143	All H-atom parameters refined
S = 1.12	w = 1/[σ²(F_o²) + (0.0668P)² + 0.3079P] where P = (F_o² + 2F_c²)/3
2190 reflections	(Δ/σ)_max < 0.001
116 parameters	Δρ_max = 0.47 e Å⁻³
0 restraints	Δρ_min = −0.31 e Å⁻³

Crystal data top

C₇H₄F₂O₂	V = 630.42 (12) Å³
M_r = 158.10	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 3.6517 (4) Å	µ = 0.16 mm⁻¹
b = 14.1214 (15) Å	T = 100 K
c = 12.2850 (13) Å	0.73 × 0.19 × 0.09 mm
β = 95.651 (3)°

Data collection top

Bruker APEXII DUO CCD diffractometer	2190 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2009)	1895 reflections with I > 2σ(I)
T_min = 0.841, T_max = 0.986	R_int = 0.029
6112 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.049	0 restraints
wR(F²) = 0.143	All H-atom parameters refined
S = 1.12	Δρ_max = 0.47 e Å⁻³
2190 reflections	Δρ_min = −0.31 e Å⁻³
116 parameters

Special details top

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K.

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.

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

	x	y	z	U_iso*/U_eq
F1	0.0410 (3)	−0.01635 (6)	0.16839 (7)	0.0312 (2)
F2	0.2348 (3)	0.26707 (6)	0.36896 (7)	0.0285 (2)
O2	0.2287 (3)	0.09843 (7)	0.46658 (7)	0.0238 (2)
O3	0.4751 (3)	−0.00746 (7)	0.35958 (8)	0.0222 (2)
C1	0.0163 (4)	0.07830 (9)	0.17659 (9)	0.0194 (2)
C2	−0.1413 (4)	0.12763 (10)	0.08679 (10)	0.0228 (3)
C3	−0.1734 (4)	0.22519 (10)	0.09441 (10)	0.0234 (3)
C4	−0.0482 (4)	0.27250 (10)	0.19005 (11)	0.0230 (3)
C5	0.1044 (4)	0.22003 (9)	0.27793 (9)	0.0184 (2)
C6	0.1398 (3)	0.12160 (8)	0.27576 (9)	0.0160 (2)
C7	0.2939 (3)	0.06665 (8)	0.37288 (9)	0.0156 (2)
H2	−0.221 (7)	0.0927 (16)	0.0182 (18)	0.038 (6)*
H3	−0.285 (6)	0.2599 (15)	0.0302 (17)	0.035 (5)*
H4	−0.074 (6)	0.3406 (16)	0.1979 (18)	0.035 (5)*
H1O2	0.341 (11)	0.062 (3)	0.526 (3)	0.098 (12)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0518 (6)	0.0183 (4)	0.0219 (4)	0.0019 (4)	−0.0044 (4)	−0.0039 (3)
F2	0.0459 (6)	0.0169 (4)	0.0210 (4)	−0.0010 (4)	−0.0048 (4)	−0.0018 (3)
O2	0.0340 (6)	0.0238 (5)	0.0135 (4)	0.0038 (4)	0.0014 (4)	0.0013 (3)
O3	0.0269 (5)	0.0179 (4)	0.0216 (4)	0.0056 (4)	0.0012 (4)	0.0030 (3)
C1	0.0238 (6)	0.0181 (5)	0.0162 (5)	0.0001 (4)	0.0014 (4)	0.0003 (4)
C2	0.0242 (6)	0.0289 (6)	0.0150 (5)	−0.0002 (5)	−0.0006 (4)	0.0019 (4)
C3	0.0224 (6)	0.0289 (6)	0.0184 (5)	0.0037 (5)	−0.0001 (4)	0.0078 (4)
C4	0.0272 (6)	0.0193 (6)	0.0225 (6)	0.0041 (5)	0.0016 (5)	0.0062 (4)
C5	0.0210 (5)	0.0174 (5)	0.0166 (5)	0.0004 (4)	0.0012 (4)	0.0011 (4)
C6	0.0182 (5)	0.0160 (5)	0.0137 (4)	0.0009 (4)	0.0014 (4)	0.0019 (3)
C7	0.0174 (5)	0.0148 (5)	0.0148 (4)	−0.0006 (4)	0.0020 (4)	0.0012 (3)

Geometric parameters (Å, º) top

F1—C1	1.3442 (15)	C2—H2	0.99 (2)
F2—C5	1.3467 (14)	C3—C4	1.3892 (19)
O2—C7	1.2794 (14)	C3—H3	0.98 (2)
O2—H1O2	0.96 (4)	C4—C5	1.3807 (17)
O3—C7	1.2574 (15)	C4—H4	0.97 (2)
C1—C2	1.3815 (17)	C5—C6	1.3965 (17)
C1—C6	1.3976 (16)	C6—C7	1.4866 (15)
C2—C3	1.387 (2)

C7—O2—H1O2	113 (2)	C5—C4—H4	119.3 (13)
F1—C1—C2	117.86 (11)	C3—C4—H4	122.2 (13)
F1—C1—C6	118.83 (11)	F2—C5—C4	117.84 (11)
C2—C1—C6	123.29 (12)	F2—C5—C6	118.74 (10)
C1—C2—C3	118.58 (12)	C4—C5—C6	123.38 (11)
C1—C2—H2	119.4 (13)	C5—C6—C1	115.44 (10)
C3—C2—H2	122.0 (13)	C5—C6—C7	122.18 (10)
C2—C3—C4	120.79 (11)	C1—C6—C7	122.37 (11)
C2—C3—H3	118.2 (13)	O3—C7—O2	123.76 (11)
C4—C3—H3	121.0 (13)	O3—C7—C6	119.51 (10)
C5—C4—C3	118.49 (12)	O2—C7—C6	116.72 (10)

F1—C1—C2—C3	179.13 (13)	C4—C5—C6—C7	−177.92 (12)
C6—C1—C2—C3	1.2 (2)	F1—C1—C6—C5	−179.87 (12)
C1—C2—C3—C4	0.3 (2)	C2—C1—C6—C5	−1.92 (19)
C2—C3—C4—C5	−0.9 (2)	F1—C1—C6—C7	−0.65 (19)
C3—C4—C5—F2	178.01 (12)	C2—C1—C6—C7	177.31 (12)
C3—C4—C5—C6	0.0 (2)	C5—C6—C7—O3	−147.25 (13)
F2—C5—C6—C1	−176.65 (11)	C1—C6—C7—O3	33.57 (18)
C4—C5—C6—C1	1.31 (19)	C5—C6—C7—O2	33.33 (17)
F2—C5—C6—C7	4.12 (18)	C1—C6—C7—O2	−145.84 (13)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H1O2···O3ⁱ	0.95 (4)	1.68 (4)	2.6318 (14)	174 (4)
C3—H3···F2ⁱⁱ	0.98 (2)	2.54 (2)	3.3428 (16)	138.7 (16)

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

Experimental details

Crystal data
Chemical formula	C₇H₄F₂O₂
M_r	158.10
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	100
a, b, c (Å)	3.6517 (4), 14.1214 (15), 12.2850 (13)
β (°)	95.651 (3)
V (Å³)	630.42 (12)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.16
Crystal size (mm)	0.73 × 0.19 × 0.09

Data collection
Diffractometer	Bruker APEXII DUO CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2009)
T_min, T_max	0.841, 0.986
No. of measured, independent and observed [I > 2σ(I)] reflections	6112, 2190, 1895
R_int	0.029
(sin θ/λ)_max (Å⁻¹)	0.749

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.049, 0.143, 1.12
No. of reflections	2190
No. of parameters	116
H-atom treatment	All H-atom parameters refined
Δρ_max, Δρ_min (e Å⁻³)	0.47, −0.31

Computer programs: APEX2 (Bruker, 2009), SAINT (Bruker, 2009), SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H1O2···O3ⁱ	0.95 (4)	1.68 (4)	2.6318 (14)	174 (4)
C3—H3···F2ⁱⁱ	0.98 (2)	2.54 (2)	3.3428 (16)	138.7 (16)

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

Footnotes

‡Thomson Reuters ResearcherID: A-5523-2009.

§Thomson Reuters ResearcherID: A-3561-2009.

Acknowledgements

NM gratefully acknowledges funding from Universiti Sains Malaysia (USM) under the University Research Grant (No. 1001/PFARMASI/815025). HKF and CSY thank USM for the Research University Golden Goose Grant (No. 1001/PFIZIK/811012). CSY also thanks USM for the award of a USM Fellowship.

References

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