organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

3,4-Di­fluoro-2-hy­dr­oxy­benzoic acid

aDepartment of Chemistry, U.C.S., Tumkur University, Tumkur, Karnataka 572 103, India, bDepartment of Studies and Research in Physics, U.C.S., Tumkur University, Tumkur, Karnataka 572 103, India, and cDepartment of Chemistry, G.F.G.C., Tumkur, Karnataka, 572 102, India
*Correspondence e-mail: vijaykumargr18@yahoo.co.in

(Received 14 March 2014; accepted 1 April 2014; online 5 April 2014)

In the title compound, C7H4F2O3, an intra­molecular O—H⋯O hydrogen bond is observed. In the crystal, inversion dimers linked by pairs of O—H⋯O hydrogen bonds generate R22(8) ring motifs. These dimers are linked by C—H⋯O and C—H⋯F hydrogen bonds, forming sheets lying parallel to (30-1). The sheets are linked by aromatic ππ stacking inter­actions [inter-centroid distance = 3.7817 (9) Å], forming a three-dimensional structure.

Related literature

For anti­body and gene-directed enzyme prodrug therapy, see: Springer et al. (1994[Springer, C. J., Ion, N. D. & Barbara, P. R. (1994). J. Med. Chem. 37, 2361-2370.]); Davies et al. (2005[Davies, L. C., Frank, F., Douglas, H., Jan, M., Ogilvie, L. M., Scanlon, I. J. & Springer, C. J. (2005). J. Med. Chem. 48, 5321-5328.]). For the anti­microbial activity of fluorinated benzoic acid derivatives, see: Rajasekhar et al. (2013[Rajasekhar, N., Chandrasekhar, K. B., Sandeep, M., Rameswara Rao, M. & Balram, B. (2013). J. Appl. Chem. 2, 1489-1498.]).

[Scheme 1]

Experimental

Crystal data
  • C7H4F2O3

  • Mr = 174.10

  • Monoclinic, P 21 /n

  • a = 9.4252 (8) Å

  • b = 6.8145 (5) Å

  • c = 11.0391 (8) Å

  • β = 106.257 (5)°

  • V = 680.67 (9) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.17 mm−1

  • T = 296 K

  • 0.20 × 0.16 × 0.12 mm

Data collection
  • Bruker APEXII CCD area-detector diffractometer

  • Absorption correction: multi-scan (SADABS; Sheldrick, 2007[Sheldrick, G. M. (2007). SADABS. University of Göttingen, Germany.]) Tmin = 0.967, Tmax = 0.980

  • 6362 measured reflections

  • 1344 independent reflections

  • 1045 reflections with I > 2σ(I)

  • Rint = 0.037

Refinement
  • R[F2 > 2σ(F2)] = 0.031

  • wR(F2) = 0.094

  • S = 1.09

  • 1344 reflections

  • 112 parameters

  • H-atom parameters constrained

  • Δρmax = 0.19 e Å−3

  • Δρmin = −0.14 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O3—H3A⋯O1 0.82 1.92 2.6231 (14) 144
O2—H2⋯O1i 0.82 1.85 2.6679 (14) 175
C3—H3⋯O3ii 0.93 2.60 3.5269 (16) 177
C4—H4⋯F2ii 0.93 2.53 3.2047 (16) 129
Symmetry codes: (i) -x+1, -y+1, -z; (ii) x, y-1, z.

Data collection: APEX2 (Bruker, 2009[Bruker (2009). APEX2, SAINT-Plus and XPREP. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: APEX2 and SAINT-Plus (Bruker, 2009[Bruker (2009). APEX2, SAINT-Plus and XPREP. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT-Plus and XPREP (Bruker, 2009[Bruker (2009). APEX2, SAINT-Plus and XPREP. Bruker AXS Inc., Madison, Wisconsin, USA.]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]) and Mercury (Macrae et al., 2008[Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.]); software used to prepare material for publication: SHELXL97.

Supporting information


Comment top

Fluorinated benzoic acids have been used for the preparation of potential prodrugs intended for antibody and gene directed enzyme prodrugtherapy (Springer et al., 1994; Davies et al., 2005). Derivatives of fluorinated benzoic acid exhibit antimicrobial activity (Rajasekhar et al., 2013). In particular 3,4-difluoro-2-hydroxybenzoic acid has been used in the synthesis of benzisoxazole containing barbiturate derivatives, which shows prominent anticancer activity (our unpublished results). Hence, the crystal structure of the title compound, (I), C7H4F2O3, is determined.

In (I), the molecule is planar (r.m.s. deviation in the benzene ring = 0.006 (1)Å with a maximum deviation of 0.009 (1)Å for carbon) (Fig. 1). An intramolecular O3—H3A···O1 hydrogen bond in observed. In the crystal, inversion dimers linked by pairs of O2—H2···O1 hydrogen bonds are formed and generate R22(8) ring motifs (Fig. 2). Weak C3—H3···O3 and C4—H4···F2 intermolecular interactions and aromatic π-π stacking interactions [centroid-centroid separation = 3.7817 (9) Å] (Fig. 3) are also observed and contribute to packing stability.

Related literature top

For antibody and gene-directed enzyme prodrug therapy, see: Springer et al. (1994); Davies et al. (2005). For the antimicrobial activity of fluorinated benzoic acid derivatives, see: Rajasekhar et al. (2013).

Experimental top

To an ice cooled and stirred solution of 2,3,4-trifluorobenzoic acid (0.028 mmol) in dimethylimidazolidinone (10 ml), solid sodium hydroxide (0.113 mmol) was added in portions, and the mixture was heated to 120°C for 2 h. The reaction was monitored by TLC. After the reaction was completed, the mixture was cooled to room temperature and neutralized (pH 5–6) with 2 N hydrochloric acid (7.5 ml). The title compound was separated out as white solid, filtered, washed with excess of water and dried. Colourless prisms of the title compound were grown in ethanol by slow the evaporation technique.

Refinement top

The hydroxy H-atoms were located in a difference Fourier map, and were refined isotropically with the O–H distance restrained to 0.82±0.01 Å. H atoms were positioned with idealized geometry using a riding model with C—H = 0.93 Å and were refined with isotropic displacement parameters (set to 1.2 times of the Ueq of the parent atom).

Computing details top

Data collection: APEX2 (Bruker, 2009); cell refinement: APEX2 and SAINT-Plus (Bruker, 2009); data reduction: SAINT-Plus and XPREP (Bruker, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. Molecular structure of the title compound, showing displacement ellipsoids drawn at the 50% probability level.
[Figure 2] Fig. 2. Molecular packing of the title compound viewed along the b axis. Dashed lines indicate O—H···O intramolecular and pairs of O—H···O intermolecular hydrogen bonds forming R22(8) ring motifs and weak C—H···O and C—H···F intermolecular interactions along [010].
[Figure 3] Fig. 3. Molecules displaying weak π-π interactions [centroid-centroid separation = 3.7817 (9) Å].
3,4-Difluoro-2-hydroxybenzoic acid top
Crystal data top
C7H4F2O3Prism
Mr = 174.10Dx = 1.699 Mg m3
Monoclinic, P21/nMelting point: 448 K
Hall symbol: -P 2ynMo Kα radiation, λ = 0.71073 Å
a = 9.4252 (8) ÅCell parameters from 1045 reflections
b = 6.8145 (5) Åθ = 2.3–26.5°
c = 11.0391 (8) ŵ = 0.17 mm1
β = 106.257 (5)°T = 296 K
V = 680.67 (9) Å3Prism, colourless
Z = 40.20 × 0.16 × 0.12 mm
F(000) = 352
Data collection top
Bruker APEXII CCD area-detector
diffractometer
1344 independent reflections
Radiation source: fine-focus sealed tube1045 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.037
Detector resolution: 1.6 pixels mm-1θmax = 26.0°, θmin = 2.5°
phi and ω scansh = 1111
Absorption correction: multi-scan
(SADABS; Sheldrick, 2007)
k = 88
Tmin = 0.967, Tmax = 0.980l = 1313
6362 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.031H-atom parameters constrained
wR(F2) = 0.094 w = 1/[σ2(Fo2) + (0.0514P)2 + 0.0514P]
where P = (Fo2 + 2Fc2)/3
S = 1.09(Δ/σ)max < 0.001
1344 reflectionsΔρmax = 0.19 e Å3
112 parametersΔρmin = 0.14 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 constraintsExtinction coefficient: 0.018 (3)
Primary atom site location: structure-invariant direct methods
Crystal data top
C7H4F2O3V = 680.67 (9) Å3
Mr = 174.10Z = 4
Monoclinic, P21/nMo Kα radiation
a = 9.4252 (8) ŵ = 0.17 mm1
b = 6.8145 (5) ÅT = 296 K
c = 11.0391 (8) Å0.20 × 0.16 × 0.12 mm
β = 106.257 (5)°
Data collection top
Bruker APEXII CCD area-detector
diffractometer
1344 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 2007)
1045 reflections with I > 2σ(I)
Tmin = 0.967, Tmax = 0.980Rint = 0.037
6362 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0310 restraints
wR(F2) = 0.094H-atom parameters constrained
S = 1.09Δρmax = 0.19 e Å3
1344 reflectionsΔρmin = 0.14 e Å3
112 parameters
Special details top

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.

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 > 2sigma(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
C10.55955 (13)0.54118 (17)0.18180 (14)0.0376 (3)
C20.60924 (12)0.57452 (17)0.31759 (13)0.0357 (3)
C30.64443 (13)0.41737 (18)0.40234 (13)0.0400 (3)
H30.63430.28970.37130.046 (4)*
C40.69337 (14)0.44745 (19)0.52991 (15)0.0458 (4)
H40.71800.34200.58540.065 (5)*
C50.70534 (14)0.63748 (19)0.57424 (14)0.0443 (3)
C60.67106 (15)0.79441 (18)0.49292 (15)0.0441 (4)
C70.62456 (13)0.76688 (16)0.36434 (14)0.0380 (3)
O10.53519 (11)0.67798 (13)0.10424 (9)0.0482 (3)
O20.54221 (10)0.35741 (12)0.14643 (10)0.0503 (3)
H20.51390.35160.06920.075*
O30.59795 (11)0.92951 (13)0.29161 (10)0.0543 (3)
H3A0.57080.89760.21700.081*
F10.75075 (11)0.67350 (13)0.69839 (8)0.0676 (3)
F20.68666 (12)0.97767 (11)0.54053 (10)0.0686 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0438 (6)0.0373 (7)0.0310 (9)0.0007 (5)0.0095 (6)0.0010 (5)
C20.0417 (6)0.0361 (7)0.0292 (9)0.0008 (4)0.0096 (6)0.0007 (5)
C30.0536 (7)0.0331 (6)0.0325 (9)0.0016 (5)0.0107 (6)0.0007 (5)
C40.0604 (8)0.0391 (7)0.0356 (10)0.0030 (5)0.0095 (7)0.0064 (5)
C50.0544 (7)0.0511 (8)0.0248 (9)0.0034 (5)0.0065 (6)0.0039 (6)
C60.0569 (7)0.0347 (7)0.0395 (10)0.0068 (5)0.0113 (7)0.0071 (5)
C70.0470 (7)0.0337 (6)0.0323 (10)0.0032 (5)0.0097 (6)0.0017 (5)
O10.0712 (6)0.0401 (5)0.0296 (7)0.0009 (4)0.0077 (5)0.0017 (4)
O20.0771 (6)0.0378 (5)0.0319 (7)0.0016 (4)0.0087 (5)0.0040 (4)
O30.0836 (7)0.0340 (5)0.0402 (7)0.0031 (4)0.0091 (6)0.0042 (4)
F10.0996 (7)0.0677 (6)0.0287 (6)0.0032 (5)0.0065 (5)0.0070 (4)
F20.1113 (7)0.0403 (5)0.0474 (7)0.0096 (4)0.0111 (6)0.0140 (4)
Geometric parameters (Å, º) top
C1—O11.2429 (15)C4—H40.9300
C1—O11.2429 (15)C5—F11.3392 (16)
C1—O21.3083 (14)C5—C61.375 (2)
C1—C21.458 (2)C6—F21.3469 (14)
C2—C31.3994 (18)C6—C71.376 (2)
C2—C71.4014 (17)C7—O31.3502 (16)
C3—C41.369 (2)O2—H20.8200
C3—H30.9300O3—H3A0.8200
C4—C51.3777 (19)
O1—C1—O2121.92 (13)C5—C4—H4120.8
O1—C1—O2121.92 (13)F1—C5—C6118.35 (12)
O1—C1—C2122.39 (11)F1—C5—C4120.45 (12)
O1—C1—C2122.39 (11)C6—C5—C4121.21 (14)
O2—C1—C2115.69 (11)F2—C6—C5119.09 (14)
C3—C2—C7119.27 (13)F2—C6—C7119.82 (12)
C3—C2—C1121.06 (11)C5—C6—C7121.06 (12)
C7—C2—C1119.66 (11)O3—C7—C6117.00 (12)
C4—C3—C2121.45 (12)O3—C7—C2124.47 (14)
C4—C3—H3119.3C6—C7—C2118.53 (12)
C2—C3—H3119.3C1—O2—H2109.5
C3—C4—C5118.46 (13)C7—O3—H3A109.5
C3—C4—H4120.8
O1—C1—C2—C3176.05 (11)F1—C5—C6—C7179.65 (11)
O1—C1—C2—C3176.05 (11)C4—C5—C6—C70.5 (2)
O2—C1—C2—C33.89 (17)F2—C6—C7—O30.61 (19)
O1—C1—C2—C72.86 (17)C5—C6—C7—O3177.90 (11)
O1—C1—C2—C72.86 (17)F2—C6—C7—C2179.95 (10)
O2—C1—C2—C7177.19 (10)C5—C6—C7—C21.5 (2)
C7—C2—C3—C40.05 (18)C3—C2—C7—O3178.06 (11)
C1—C2—C3—C4178.97 (10)C1—C2—C7—O30.87 (18)
C2—C3—C4—C51.03 (19)C3—C2—C7—C61.33 (18)
C3—C4—C5—F1179.05 (11)C1—C2—C7—C6179.74 (10)
C3—C4—C5—C60.8 (2)O2—C1—O1—O10.00 (14)
F1—C5—C6—F21.1 (2)C2—C1—O1—O10.00 (14)
C4—C5—C6—F2178.98 (12)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3A···O10.821.922.6231 (14)144
O2—H2···O1i0.821.852.6679 (14)175
C3—H3···O3ii0.932.603.5269 (16)177
C4—H4···F2ii0.932.533.2047 (16)129
Symmetry codes: (i) x+1, y+1, z; (ii) x, y1, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3A···O10.821.922.6231 (14)143.9
O2—H2···O1i0.821.852.6679 (14)174.5
C3—H3···O3ii0.932.603.5269 (16)177.2
C4—H4···F2ii0.932.533.2047 (16)129.4
Symmetry codes: (i) x+1, y+1, z; (ii) x, y1, z.
 

Acknowledgements

The authors thank the DST–SERB (SR/FT/CS-145/2010) for finacial support and Dr S. Karmakar and Kibriya Siddique, SAIF, Gauhati University, Guwahati, India, for their help with the data collection.

References

First citationBruker (2009). APEX2, SAINT-Plus and XPREP. Bruker AXS Inc., Madison, Wisconsin, USA.
First citationDavies, L. C., Frank, F., Douglas, H., Jan, M., Ogilvie, L. M., Scanlon, I. J. & Springer, C. J. (2005). J. Med. Chem. 48, 5321–5328.  Web of Science CrossRef PubMed CAS
First citationFarrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.  Web of Science CrossRef CAS IUCr Journals
First citationMacrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466–470.  Web of Science CrossRef CAS IUCr Journals
First citationRajasekhar, N., Chandrasekhar, K. B., Sandeep, M., Rameswara Rao, M. & Balram, B. (2013). J. Appl. Chem. 2, 1489–1498.
First citationSheldrick, G. M. (2007). SADABS. University of Göttingen, Germany.
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationSpringer, C. J., Ion, N. D. & Barbara, P. R. (1994). J. Med. Chem. 37, 2361–2370.  CrossRef CAS PubMed Web of Science

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Follow Acta Cryst. E
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds