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ISSN: 2056-9890

2,6-Di­fluoro­benzoic acid

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, J. A. (1995). Physiol. Rev. 75, 725-748.]); Beavo & Reifsnyder (1990[Beavo, J. A. & Reifsnyder, D. H. (1990). Trends Pharmacol. Sci. 11, 150-155.]); Nicholson et al. (1991[Nicholson, C. D., Chaliss, R. A. & Shalid, M. (1991). Trends Pharmacol. Sci. 12, 19-27.]). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986[Cosier, J. & Glazer, A. M. (1986). J. Appl. Cryst. 19, 105-107.]).

[Scheme 1]

Experimental

Crystal data
  • C7H4F2O2

  • Mr = 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[Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.841, Tmax = 0.986

  • 6112 measured reflections

  • 2190 independent reflections

  • 1895 reflections with I > 2σ(I)

  • Rint = 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

  • Δρmax = 0.47 e Å−3

  • Δρmin = −0.31 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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[Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2009[Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]).

Supporting information


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.

Refinement top

All hydrogen atoms were located in a difference Fourier map and refined freely.

Structure description 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).

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
[Figure 1] Fig. 1. The molecular structure of (I) with 50% probability ellipsoids for non-H atoms.
[Figure 2] 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
C7H4F2O2F(000) = 320
Mr = 158.10Dx = 1.666 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 3166 reflections
a = 3.6517 (4) Åθ = 3.3–32.1°
b = 14.1214 (15) ŵ = 0.16 mm1
c = 12.2850 (13) ÅT = 100 K
β = 95.651 (3)°Needle, colourless
V = 630.42 (12) Å30.73 × 0.19 × 0.09 mm
Z = 4
Data collection top
Bruker APEXII DUO CCD
diffractometer
2190 independent reflections
Radiation source: fine-focus sealed tube1895 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.029
φ and ω scansθmax = 32.1°, θmin = 2.2°
Absorption correction: multi-scan
(SADABS; Bruker, 2009)
h = 55
Tmin = 0.841, Tmax = 0.986k = 2020
6112 measured reflectionsl = 1818
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.049Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.143All H-atom parameters refined
S = 1.12 w = 1/[σ2(Fo2) + (0.0668P)2 + 0.3079P]
where P = (Fo2 + 2Fc2)/3
2190 reflections(Δ/σ)max < 0.001
116 parametersΔρmax = 0.47 e Å3
0 restraintsΔρmin = 0.31 e Å3
Crystal data top
C7H4F2O2V = 630.42 (12) Å3
Mr = 158.10Z = 4
Monoclinic, P21/cMo Kα radiation
a = 3.6517 (4) ŵ = 0.16 mm1
b = 14.1214 (15) ÅT = 100 K
c = 12.2850 (13) Å0.73 × 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)
Tmin = 0.841, Tmax = 0.986Rint = 0.029
6112 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0490 restraints
wR(F2) = 0.143All H-atom parameters refined
S = 1.12Δρmax = 0.47 e Å3
2190 reflectionsΔρmin = 0.31 e Å3
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
xyzUiso*/Ueq
F10.0410 (3)0.01635 (6)0.16839 (7)0.0312 (2)
F20.2348 (3)0.26707 (6)0.36896 (7)0.0285 (2)
O20.2287 (3)0.09843 (7)0.46658 (7)0.0238 (2)
O30.4751 (3)0.00746 (7)0.35958 (8)0.0222 (2)
C10.0163 (4)0.07830 (9)0.17659 (9)0.0194 (2)
C20.1413 (4)0.12763 (10)0.08679 (10)0.0228 (3)
C30.1734 (4)0.22519 (10)0.09441 (10)0.0234 (3)
C40.0482 (4)0.27250 (10)0.19005 (11)0.0230 (3)
C50.1044 (4)0.22003 (9)0.27793 (9)0.0184 (2)
C60.1398 (3)0.12160 (8)0.27576 (9)0.0160 (2)
C70.2939 (3)0.06665 (8)0.37288 (9)0.0156 (2)
H20.221 (7)0.0927 (16)0.0182 (18)0.038 (6)*
H30.285 (6)0.2599 (15)0.0302 (17)0.035 (5)*
H40.074 (6)0.3406 (16)0.1979 (18)0.035 (5)*
H1O20.341 (11)0.062 (3)0.526 (3)0.098 (12)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0518 (6)0.0183 (4)0.0219 (4)0.0019 (4)0.0044 (4)0.0039 (3)
F20.0459 (6)0.0169 (4)0.0210 (4)0.0010 (4)0.0048 (4)0.0018 (3)
O20.0340 (6)0.0238 (5)0.0135 (4)0.0038 (4)0.0014 (4)0.0013 (3)
O30.0269 (5)0.0179 (4)0.0216 (4)0.0056 (4)0.0012 (4)0.0030 (3)
C10.0238 (6)0.0181 (5)0.0162 (5)0.0001 (4)0.0014 (4)0.0003 (4)
C20.0242 (6)0.0289 (6)0.0150 (5)0.0002 (5)0.0006 (4)0.0019 (4)
C30.0224 (6)0.0289 (6)0.0184 (5)0.0037 (5)0.0001 (4)0.0078 (4)
C40.0272 (6)0.0193 (6)0.0225 (6)0.0041 (5)0.0016 (5)0.0062 (4)
C50.0210 (5)0.0174 (5)0.0166 (5)0.0004 (4)0.0012 (4)0.0011 (4)
C60.0182 (5)0.0160 (5)0.0137 (4)0.0009 (4)0.0014 (4)0.0019 (3)
C70.0174 (5)0.0148 (5)0.0148 (4)0.0006 (4)0.0020 (4)0.0012 (3)
Geometric parameters (Å, º) top
F1—C11.3442 (15)C2—H20.99 (2)
F2—C51.3467 (14)C3—C41.3892 (19)
O2—C71.2794 (14)C3—H30.98 (2)
O2—H1O20.96 (4)C4—C51.3807 (17)
O3—C71.2574 (15)C4—H40.97 (2)
C1—C21.3815 (17)C5—C61.3965 (17)
C1—C61.3976 (16)C6—C71.4866 (15)
C2—C31.387 (2)
C7—O2—H1O2113 (2)C5—C4—H4119.3 (13)
F1—C1—C2117.86 (11)C3—C4—H4122.2 (13)
F1—C1—C6118.83 (11)F2—C5—C4117.84 (11)
C2—C1—C6123.29 (12)F2—C5—C6118.74 (10)
C1—C2—C3118.58 (12)C4—C5—C6123.38 (11)
C1—C2—H2119.4 (13)C5—C6—C1115.44 (10)
C3—C2—H2122.0 (13)C5—C6—C7122.18 (10)
C2—C3—C4120.79 (11)C1—C6—C7122.37 (11)
C2—C3—H3118.2 (13)O3—C7—O2123.76 (11)
C4—C3—H3121.0 (13)O3—C7—C6119.51 (10)
C5—C4—C3118.49 (12)O2—C7—C6116.72 (10)
F1—C1—C2—C3179.13 (13)C4—C5—C6—C7177.92 (12)
C6—C1—C2—C31.2 (2)F1—C1—C6—C5179.87 (12)
C1—C2—C3—C40.3 (2)C2—C1—C6—C51.92 (19)
C2—C3—C4—C50.9 (2)F1—C1—C6—C70.65 (19)
C3—C4—C5—F2178.01 (12)C2—C1—C6—C7177.31 (12)
C3—C4—C5—C60.0 (2)C5—C6—C7—O3147.25 (13)
F2—C5—C6—C1176.65 (11)C1—C6—C7—O333.57 (18)
C4—C5—C6—C11.31 (19)C5—C6—C7—O233.33 (17)
F2—C5—C6—C74.12 (18)C1—C6—C7—O2145.84 (13)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O2—H1O2···O3i0.95 (4)1.68 (4)2.6318 (14)174 (4)
C3—H3···F2ii0.98 (2)2.54 (2)3.3428 (16)138.7 (16)
Symmetry codes: (i) x+1, y, z+1; (ii) x1, y+1/2, z1/2.

Experimental details

Crystal data
Chemical formulaC7H4F2O2
Mr158.10
Crystal system, space groupMonoclinic, P21/c
Temperature (K)100
a, b, c (Å)3.6517 (4), 14.1214 (15), 12.2850 (13)
β (°) 95.651 (3)
V3)630.42 (12)
Z4
Radiation typeMo Kα
µ (mm1)0.16
Crystal size (mm)0.73 × 0.19 × 0.09
Data collection
DiffractometerBruker APEXII DUO CCD
Absorption correctionMulti-scan
(SADABS; Bruker, 2009)
Tmin, Tmax0.841, 0.986
No. of measured, independent and
observed [I > 2σ(I)] reflections
6112, 2190, 1895
Rint0.029
(sin θ/λ)max1)0.749
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.049, 0.143, 1.12
No. of reflections2190
No. of parameters116
H-atom treatmentAll H-atom parameters refined
Δρmax, Δρmin (e Å3)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···AD—HH···AD···AD—H···A
O2—H1O2···O3i0.95 (4)1.68 (4)2.6318 (14)174 (4)
C3—H3···F2ii0.98 (2)2.54 (2)3.3428 (16)138.7 (16)
Symmetry codes: (i) x+1, y, z+1; (ii) x1, y+1/2, z1/2.
 

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

First citationBeavo, J. A. (1995). Physiol. Rev. 75, 725–748.  CAS PubMed Web of Science Google Scholar
First citationBeavo, J. A. & Reifsnyder, D. H. (1990). Trends Pharmacol. Sci. 11, 150–155.  CrossRef CAS PubMed Web of Science Google Scholar
First citationBruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationCosier, J. & Glazer, A. M. (1986). J. Appl. Cryst. 19, 105–107.  CrossRef CAS Web of Science IUCr Journals Google Scholar
First citationNicholson, C. D., Chaliss, R. A. & Shalid, M. (1991). Trends Pharmacol. Sci. 12, 19–27.  CrossRef PubMed CAS Web of Science Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals Google Scholar

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ISSN: 2056-9890
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