2-Amino-5-fluoro­benzoic acid

Sreenivasa, S.; ManojKumar, K.E.; Suchetan, P.A.; Palakshamurthy, B.S.; Gunasekaran, K.

doi:10.1107/S160053681300408X

organic compounds

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ISSN: 2056-9890

Volume 69| Part 3| March 2013| Page o387

doi:10.1107/S160053681300408X

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2-Amino-5-fluorobenzoic acid

S. Sreenivasa,^a ^* K.E. ManojKumar,^a P.A. Suchetan,^b B. S. Palakshamurthy ^c and K. Gunasekaran ^d

^aDepartment of Studies and Research in Chemistry, Tumkur University, Tumkur, Karnataka 572 103, India, ^bDepartment of Studies and Research in Chemistry, U.C.S., Tumkur University, Tumkur, Karnataka 572 103, India, ^cDepartment of Studies and Research in Physics, U.C.S., Tumkur University, Tumkur, Karnataka 572 103, India, and ^dCentre of Advanced Study in Crystallography and Biophysics, University of Madras Guindy Campus, Chennai 600 025, India
^*Correspondence e-mail: drsreenivasa@yahoo.co.in

(Received 10 February 2013; accepted 11 February 2013; online 16 February 2013)

In the title compound, C₇H₆FNO₂, the molecule is almost planar (r.m.s. deviation for the non-H atoms = 0.015 Å) and an intramolecular N—H⋯O hydrogen bond closes an S(6) ring. In the crystal, inversion dimers linked by pairs of O—H⋯O hydrogen bonds generate R₂²(8) loops. Weak N—H⋯F hydrogen bonds, short F⋯F contacts [2.763 (2) Å] and aromatic π–π stacking interactions [centroid–centroid separation = 3.5570 (11) Å] are also observed in the crystal structure.

Related literature

For the applications of the title compound in the field of genetics, see: Toyn et al. (2000 ).

Experimental

Crystal data

C₇H₆FNO₂
M_r = 155.13
Monoclinic, P 2₁ /c
a = 4.9346 (2) Å
b = 11.7542 (6) Å
c = 11.9727 (5) Å
β = 96.782 (3)°
V = 689.58 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.13 mm⁻¹
T = 293 K
0.43 × 0.37 × 0.25 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2004 ) T_min = 0.947, T_max = 0.969
5184 measured reflections
1207 independent reflections
1057 reflections with I > 2σ(I)
R_int = 0.025

Refinement

R[F² > 2σ(F²)] = 0.034
wR(F²) = 0.100
S = 1.09
1207 reflections
108 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.11 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1B⋯O1	0.901 (19)	2.044 (19)	2.6959 (17)	128.2 (16)
N1—H1A⋯F1ⁱ	0.91 (2)	2.55 (2)	3.3646 (17)	149.8 (14)
O2—H2⋯O1ⁱⁱ	0.82	1.81	2.6279 (12)	175
Symmetry codes: (i) $[x, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ ; (ii) -x, -y+1, -z.

Data collection: APEX2 (Bruker, 2004);; cell refinement: SAINT-Plus (Bruker, 2004); data reduction: SAINT-Plus; 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 ); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S160053681300408X/hb7040sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S160053681300408X/hb7040Isup2.hkl

Supporting information file. DOI: 10.1107/S160053681300408X/hb7040Isup3.cml

checkCIF report

Comment top

2-Amino-5-fluorobenzoic acid is used for the counterselection of TRP1, a commonly used genetic marker in the yeast Saccharomyces cerevisiae (Toyn et al., 2000). The ability to counterselect, as well as to select for, a genetic marker has numerous applications in microbial genetics. Keeping this in mind, the structure of the title compound is discussed here.

In the crystal structure of the title compound, C₇H₆FNO₂, the molecules are linked through O2—H2···O1 hydrogen bonds into inversion related dimers. N1—H1A···F1 hydrogen bonds and short F1···F1 contacts [2.763 (2) Å] are also observed in the crystal structure. Further, the structure features an intra molecular hydrogen bond between the amino proton and the adjacent carboxylic oxygen atom.

Related literature top

For the applications of the title compound in the field of genetics, see: Toyn et al. (2000).

Experimental top

4-Fluoroaniline (0.01 mmol), aluminium chloride (0.05 mmol) and trichloroacetyl chloride(0.03 mmol) were taken in dichloro methane (DCM) (20 ml) at 00 C under nitrogen atmosphere. The reaction mixture was refluxed for 16 h. The mixture was poured into ice-water carefully and the pH was adjusted to 2. The organic layer was separated and the aqueous layer was extracted with DCM. The combined extract was concentrated to get dark oily 1-(2-amino-5-fluorophenyl)-2,2,2-trichloroethanone. This compound (0.01 mmol) was dissolved in methanol. To this solution sodium methoxide (25% w/t in methanol) was added at 0 °C. The mixture was stirred for 1 h, the pH was adjusted to 6. The resulting solution was extracted with DCM and concentrated to get a brown solid methyl-2-amino-5-fluorobenzoate. To a solution of methyl-2-amino-5-fluorobenzoate (0.01 mmol) in tetrahydrofuran (10 ml),1 N Lithium hydroxide (0.03 mmol) was added at room temperature and stirred at 60 °C for 6 h. The reaction mixture was cooled to 0 °C and pH was adjusted to 5, the precipitate obtained was collected and dried in vacuum to get the title compound. Colourless prisms were obtained by slow evaporation of the solution of the compound in a mixture of DCM and methanol.

Computing details top

Data collection: APEX2 (Bruker, 2004); cell refinement: SAINT-Plus (Bruker, 2004); data reduction: SAINT-Plus (Bruker, 2004); 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); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top

	Fig. 1. Molecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level.
	Fig. 2. Molecular packing in the title compound. Hydrogen bonds are shown as dashed lines
	Fig. 3. Display of F···F contacts and O–H···O Hydrogen bonds.

2-Amino-5-fluorobenzoic acid top

Crystal data top

C₇H₆FNO₂	Prism
M_r = 155.13	D_x = 1.494 Mg m⁻³
Monoclinic, P2₁/c	Melting point: 454 K
Hall symbol: -P 2ybc	Mo Kα radiation, λ = 0.71073 Å
a = 4.9346 (2) Å	Cell parameters from 108 reflections
b = 11.7542 (6) Å	θ = 2.4–25.0°
c = 11.9727 (5) Å	µ = 0.13 mm⁻¹
β = 96.782 (3)°	T = 293 K
V = 689.58 (5) Å³	Prism, colourless
Z = 4	0.43 × 0.37 × 0.25 mm
F(000) = 320

Data collection top

Bruker APEXII CCD diffractometer	1207 independent reflections
Radiation source: fine-focus sealed tube	1057 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.025
ω scans	θ_max = 25.0°, θ_min = 2.4°
Absorption correction: multi-scan (SADABS; Bruker, 2004)	h = −5→5
T_min = 0.947, T_max = 0.969	k = −13→13
5184 measured reflections	l = −14→14

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)] = 0.034	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.100	H atoms treated by a mixture of independent and constrained refinement
S = 1.09	w = 1/[σ²(F_o²) + (0.0616P)² + 0.0629P] where P = (F_o² + 2F_c²)/3
1207 reflections	(Δ/σ)_max < 0.001
108 parameters	Δρ_max = 0.11 e Å⁻³
0 restraints	Δρ_min = −0.18 e Å⁻³
0 constraints

Crystal data top

C₇H₆FNO₂	V = 689.58 (5) Å³
M_r = 155.13	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 4.9346 (2) Å	µ = 0.13 mm⁻¹
b = 11.7542 (6) Å	T = 293 K
c = 11.9727 (5) Å	0.43 × 0.37 × 0.25 mm
β = 96.782 (3)°

Data collection top

Bruker APEXII CCD diffractometer	1207 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2004)	1057 reflections with I > 2σ(I)
T_min = 0.947, T_max = 0.969	R_int = 0.025
5184 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.034	0 restraints
wR(F²) = 0.100	H atoms treated by a mixture of independent and constrained refinement
S = 1.09	Δρ_max = 0.11 e Å⁻³
1207 reflections	Δρ_min = −0.18 e Å⁻³
108 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.

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

	x	y	z	U_iso*/U_eq
H1B	0.443 (4)	0.5012 (15)	0.2698 (16)	0.077 (5)*
H1A	0.681 (4)	0.4717 (14)	0.3630 (16)	0.078 (5)*
O1	0.20891 (18)	0.49475 (8)	0.11724 (8)	0.0572 (3)
C1	0.5279 (2)	0.34252 (10)	0.12427 (10)	0.0419 (3)
O2	0.20142 (19)	0.37877 (9)	−0.02978 (7)	0.0606 (3)
H2	0.0757	0.4209	−0.0541	0.091*
C2	0.6596 (2)	0.36817 (11)	0.23280 (10)	0.0458 (3)
C6	0.6146 (3)	0.24937 (12)	0.06514 (10)	0.0515 (3)
H6	0.5277	0.2315	−0.0059	0.062*
N1	0.5831 (3)	0.45571 (12)	0.29601 (11)	0.0688 (4)
C7	0.3008 (2)	0.41184 (10)	0.07158 (10)	0.0430 (3)
C4	0.9633 (3)	0.20846 (12)	0.21735 (11)	0.0561 (4)
H4	1.1092	0.1636	0.2474	0.067*
C3	0.8792 (3)	0.29852 (12)	0.27596 (11)	0.0529 (4)
H3	0.9699	0.3145	0.3468	0.063*
F1	0.9117 (2)	0.09467 (9)	0.05376 (8)	0.0924 (4)
C5	0.8272 (3)	0.18517 (12)	0.11232 (11)	0.0567 (4)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0586 (6)	0.0593 (6)	0.0492 (6)	0.0139 (4)	−0.0129 (4)	−0.0088 (4)
C1	0.0393 (6)	0.0479 (7)	0.0374 (6)	−0.0016 (5)	0.0000 (5)	0.0045 (5)
O2	0.0619 (6)	0.0706 (6)	0.0439 (6)	0.0196 (5)	−0.0163 (4)	−0.0100 (4)
C2	0.0430 (6)	0.0513 (7)	0.0413 (7)	−0.0038 (5)	−0.0023 (5)	0.0027 (5)
C6	0.0566 (7)	0.0593 (7)	0.0370 (6)	0.0071 (6)	−0.0017 (5)	0.0009 (6)
N1	0.0719 (8)	0.0721 (8)	0.0549 (8)	0.0145 (7)	−0.0238 (6)	−0.0188 (6)
C7	0.0407 (6)	0.0477 (7)	0.0387 (6)	−0.0033 (5)	−0.0024 (5)	0.0009 (5)
C4	0.0538 (7)	0.0674 (9)	0.0461 (7)	0.0148 (6)	0.0018 (6)	0.0161 (6)
C3	0.0507 (7)	0.0664 (8)	0.0384 (6)	0.0003 (6)	−0.0077 (5)	0.0079 (6)
F1	0.1194 (8)	0.0939 (7)	0.0597 (6)	0.0593 (6)	−0.0071 (5)	−0.0108 (5)
C5	0.0665 (8)	0.0594 (8)	0.0442 (7)	0.0186 (6)	0.0061 (6)	0.0048 (6)

Geometric parameters (Å, º) top

O1—C7	1.2299 (15)	C6—H6	0.9300
C1—C6	1.3982 (18)	N1—H1B	0.901 (19)
C1—C2	1.4150 (17)	N1—H1A	0.91 (2)
C1—C7	1.4667 (16)	C4—C3	1.361 (2)
O2—C7	1.3129 (14)	C4—C5	1.381 (2)
O2—H2	0.8200	C4—H4	0.9300
C2—N1	1.3571 (19)	C3—H3	0.9300
C2—C3	1.4069 (18)	F1—C5	1.3660 (16)
C6—C5	1.3599 (18)

C6—C1—C2	119.80 (11)	O1—C7—O2	121.90 (10)
C6—C1—C7	118.77 (10)	O1—C7—C1	123.51 (10)
C2—C1—C7	121.43 (11)	O2—C7—C1	114.59 (11)
C7—O2—H2	109.5	C3—C4—C5	118.59 (11)
N1—C2—C3	119.29 (11)	C3—C4—H4	120.7
N1—C2—C1	123.08 (11)	C5—C4—H4	120.7
C3—C2—C1	117.63 (12)	C4—C3—C2	122.10 (11)
C5—C6—C1	119.44 (12)	C4—C3—H3	119.0
C5—C6—H6	120.3	C2—C3—H3	119.0
C1—C6—H6	120.3	C6—C5—F1	119.08 (12)
C2—N1—H1B	120.5 (12)	C6—C5—C4	122.44 (13)
C2—N1—H1A	119.8 (11)	F1—C5—C4	118.48 (12)
H1B—N1—H1A	119.5 (17)

C6—C1—C2—N1	−178.62 (12)	C2—C1—C7—O2	179.10 (11)
C7—C1—C2—N1	1.46 (19)	C5—C4—C3—C2	−0.1 (2)
C6—C1—C2—C3	1.17 (18)	N1—C2—C3—C4	179.06 (13)
C7—C1—C2—C3	−178.75 (11)	C1—C2—C3—C4	−0.74 (19)
C2—C1—C6—C5	−0.75 (19)	C1—C6—C5—F1	−179.65 (12)
C7—C1—C6—C5	179.17 (11)	C1—C6—C5—C4	−0.1 (2)
C6—C1—C7—O1	179.42 (11)	C3—C4—C5—C6	0.6 (2)
C2—C1—C7—O1	−0.66 (18)	C3—C4—C5—F1	−179.91 (12)
C6—C1—C7—O2	−0.82 (16)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1B···O1	0.901 (19)	2.044 (19)	2.6959 (17)	128.2 (16)
N1—H1A···F1ⁱ	0.91 (2)	2.55 (2)	3.3646 (17)	149.8 (14)
O2—H2···O1ⁱⁱ	0.82	1.81	2.6279 (12)	175

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

Experimental details

Crystal data
Chemical formula	C₇H₆FNO₂
M_r	155.13
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	4.9346 (2), 11.7542 (6), 11.9727 (5)
β (°)	96.782 (3)
V (Å³)	689.58 (5)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.13
Crystal size (mm)	0.43 × 0.37 × 0.25

Data collection
Diffractometer	Bruker APEXII CCD diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2004)
T_min, T_max	0.947, 0.969
No. of measured, independent and observed [I > 2σ(I)] reflections	5184, 1207, 1057
R_int	0.025
(sin θ/λ)_max (Å⁻¹)	0.594

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.034, 0.100, 1.09
No. of reflections	1207
No. of parameters	108
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.11, −0.18

Computer programs: APEX2 (Bruker, 2004), SAINT-Plus (Bruker, 2004), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 2012).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1B···O1	0.901 (19)	2.044 (19)	2.6959 (17)	128.2 (16)
N1—H1A···F1ⁱ	0.91 (2)	2.55 (2)	3.3646 (17)	149.8 (14)
O2—H2···O1ⁱⁱ	0.82	1.81	2.6279 (12)	175

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

Acknowledgements

The authors thank Dr S. C. Sharma, Vice Chancellor, Tumkur University, Tumkur, for his constant encouragement. BSPM thanks Dr H. C. Devarajegowda, Department of Physics Yuvarajas College (Constituent), University of Mysore, for his guidance.

References

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