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Acta Crystallogr Sect E Struct Rep Online. 2010 November 1; 66(Pt 11): o3025.
Published online 2010 October 31. doi:  10.1107/S1600536810042510
PMCID: PMC3009038

Methyl 2-amino-5-chloro­benzoate

Abstract

The title compound, C8H8ClNO2, is almost planar, with an r.m.s. deviation of 0.0410 Å from the plane through the non-hydrogen atoms. In the crystal structure, inter­molecular N—H(...)O hydrogen bonds link the mol­ecules into chains along the b axis. An intra­molecular N—H(...)O hydrogen bond results in the formation of a six-membered ring.

Related literature

The title compound is a useful pharmaceutical inter­mediate, see: Dong & Xu (2009 [triangle]). For bond-length data, see: Allen et al. (1987 [triangle]).

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Object name is e-66-o3025-scheme1.jpg

Experimental

Crystal data

  • C8H8ClNO2
  • M r = 185.60
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o3025-efi1.jpg
  • a = 3.9480 (8) Å
  • b = 9.0230 (18) Å
  • c = 12.018 (2) Å
  • β = 94.10 (3)°
  • V = 427.02 (15) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.40 mm−1
  • T = 293 K
  • 0.30 × 0.30 × 0.05 mm

Data collection

  • Enraf–Nonius CAD-4 diffractometer
  • Absorption correction: ψ scan (North et al., 1968 [triangle]) T min = 0.889, T max = 0.980
  • 1911 measured reflections
  • 1663 independent reflections
  • 1437 reflections with I > 2σ(I)
  • R int = 0.035
  • 3 standard reflections every 200 reflections intensity decay: 1%

Refinement

  • R[F 2 > 2σ(F 2)] = 0.051
  • wR(F 2) = 0.160
  • S = 1.01
  • 1663 reflections
  • 110 parameters
  • 1 restraint
  • H-atom parameters constrained
  • Δρmax = 0.27 e Å−3
  • Δρmin = −0.19 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 777 Friedel pairs
  • Flack parameter: 0.30 (14)

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1989 [triangle]); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: PLATON (Spek, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810042510/bq2241sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810042510/bq2241Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

supplementary crystallographic information

Comment

Quinazolinones play an important role in the fields of natural products and medicinal chemistry. The title compound, methyl 2-amino-5-chlorobenzoate, (I), is a useful pharmaceutical intermediate (Dong et al. 2009). The molecule of (I) (Figure 1.) is almost planar (except the methyl hydrogens) with r. m. s. deviation of 0.0410 Å and the bond lengths (Allen et al., 1987) and angles are within normal ranges. The intramolecular N-H···O hydrogen bond (Table 1) results in the formation of a six-membered ring (C1/C6/C7/O2/H0B/N). In the crystal structure, intermolecular N-H0A···O2 hydrogen bonds link the molecules to form a stable structure (Table 1. and Figure 2.).

Experimental

The title compound, methyl 2-amino-5-chlorobenzoate was prepared by the literature method (Dong et al., 2009). To a solution of 2-aminobenzoic acid (10 g, 66 mmol) in DMF (40 mL) was added N-halosuccinimide (66 mmol) and the reaction mixture was heated at 100 °C for 40 min, cooled to room temperature, left stand overnight, and then slowly poured into ice-water (150 mL) to precipitate a white solid. The solid was filtered, washed with water (50 mL * 3), then taken up in ethyl acetate (600 mL). The ethyl acetate solution was dried over magnesium sulfate, evaporated under reduced pressure and the residual solid was washed with ether (30 mL * 3) to afford intermediate 2-amino-5-chlorobenzoic acid. To an alcohol solution (60 mL) containing 2-amino-5-chlorobenzoic acid (20 mmol) was added thionyl chloride (60 mmol), and the resulting suspension was refluxed overnight. The solvent was evaporated followed by addition of EtOAc, washed with 10% NaOH solution, dried, filtered, and evaporated to afford the desired anthranilic acid esters methyl 2-amino-5-chlorobenzoate. Crystals suitable for X-ray analysis were obtained by slow evaporation of an methanol solution.

Refinement

H atoms were positioned geometrically, with N-H = 0.86 Å (for NH2) and C-H = 0.93, 0.98 and 0.96 Å for aromatic, methine and methyl H, respectively, and constrained to ride on their parent atoms, with Uiso(H) = xUeq(C,N), where x = 1.5 for methyl H and x = 1.2 for all other H atoms.

Figures

Fig. 1.
The molecular structure of the title molecule, with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
Fig. 2.
A packing diagram of (I). Hydrogen bond is shown as dashed line.

Crystal data

C8H8ClNO2F(000) = 192
Mr = 185.60Dx = 1.444 Mg m3
Monoclinic, P21Melting point: 343 K
Hall symbol: P 2ybMo Kα radiation, λ = 0.71073 Å
a = 3.9480 (8) ÅCell parameters from 25 reflections
b = 9.0230 (18) Åθ = 10–14°
c = 12.018 (2) ŵ = 0.40 mm1
β = 94.10 (3)°T = 293 K
V = 427.02 (15) Å3Block, colourless
Z = 20.30 × 0.30 × 0.05 mm

Data collection

Enraf–Nonius CAD-4 diffractometer1437 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.035
graphiteθmax = 26.0°, θmin = 1.7°
ω/2θ scansh = 0→4
Absorption correction: ψ scan (North et al., 1968)k = −11→11
Tmin = 0.889, Tmax = 0.980l = −14→14
1911 measured reflections3 standard reflections every 200 reflections
1663 independent reflections intensity decay: 1%

Refinement

Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.051w = 1/[σ2(Fo2) + (0.1P)2 + 0.190P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.160(Δ/σ)max < 0.001
S = 1.00Δρmax = 0.27 e Å3
1663 reflectionsΔρmin = −0.19 e Å3
110 parametersExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraintExtinction coefficient: 0.103 (19)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack (1983), 777 Friedel pairs
Secondary atom site location: difference Fourier mapFlack parameter: 0.30 (14)

Special details

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)

xyzUiso*/Ueq
Cl0.5983 (3)0.76879 (13)0.57288 (9)0.0669 (4)
N0.1559 (10)0.5027 (4)0.9873 (3)0.0566 (10)
H0A0.17910.55451.04740.068*
H0B0.07000.41520.98880.068*
O10.1109 (8)0.2663 (4)0.6830 (2)0.0570 (7)
C10.2559 (10)0.5595 (4)0.8894 (3)0.0416 (8)
O2−0.0279 (9)0.2648 (4)0.8588 (2)0.0664 (8)
C20.3960 (10)0.7029 (4)0.8887 (4)0.0471 (9)
H2A0.41900.75670.95480.057*
C30.4982 (9)0.7643 (5)0.7937 (3)0.0484 (8)
H3A0.58840.85950.79540.058*
C40.4699 (10)0.6870 (4)0.6945 (3)0.0459 (9)
C50.3416 (10)0.5457 (4)0.6914 (3)0.0437 (9)
H5A0.32660.49320.62460.052*
C60.2327 (9)0.4797 (4)0.7884 (3)0.0410 (8)
C70.0929 (10)0.3288 (4)0.7827 (3)0.0425 (8)
C8−0.0251 (14)0.1186 (5)0.6689 (4)0.0650 (13)
H8A0.00200.08530.59410.097*
H8B−0.26190.11920.68220.097*
H8C0.09420.05280.72080.097*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl0.0859 (8)0.0590 (6)0.0578 (6)−0.0183 (6)0.0195 (5)0.0133 (5)
N0.082 (3)0.049 (2)0.0405 (18)0.0089 (18)0.0160 (17)0.0031 (16)
O10.0802 (18)0.0415 (13)0.0503 (14)−0.0169 (17)0.0130 (13)−0.0067 (15)
C10.048 (2)0.0374 (18)0.0394 (19)0.0079 (16)0.0049 (16)0.0026 (15)
O20.099 (2)0.0470 (16)0.0564 (16)−0.009 (2)0.0251 (15)0.0092 (17)
C20.052 (2)0.042 (2)0.048 (2)0.0045 (17)0.0046 (16)−0.0069 (17)
C30.050 (2)0.0359 (17)0.059 (2)−0.002 (2)0.0056 (16)−0.002 (2)
C40.048 (2)0.043 (2)0.048 (2)−0.0020 (18)0.0067 (16)0.0090 (17)
C50.050 (2)0.041 (2)0.041 (2)−0.0016 (16)0.0110 (16)−0.0016 (16)
C60.0412 (19)0.0360 (18)0.046 (2)0.0028 (15)0.0068 (15)0.0057 (15)
C70.048 (2)0.0347 (17)0.045 (2)0.0013 (16)0.0053 (16)0.0034 (15)
C80.080 (3)0.042 (2)0.073 (3)−0.018 (2)0.007 (3)−0.008 (2)

Geometric parameters (Å, °)

Cl—C41.744 (4)C2—H2A0.9300
N—C11.367 (5)C3—C41.379 (6)
N—H0A0.8600C3—H3A0.9300
N—H0B0.8600C4—C51.372 (5)
O1—C71.330 (5)C5—C61.403 (5)
O1—C81.443 (5)C5—H5A0.9300
C1—C21.408 (6)C6—C71.469 (5)
C1—C61.409 (5)C8—H8A0.9600
O2—C71.208 (5)C8—H8B0.9600
C2—C31.357 (6)C8—H8C0.9600
C1—N—H0A120.0C4—C5—C6120.4 (4)
C1—N—H0B120.0C4—C5—H5A119.8
H0A—N—H0B120.0C6—C5—H5A119.8
C7—O1—C8117.0 (3)C5—C6—C1119.6 (3)
N—C1—C2119.1 (4)C5—C6—C7119.4 (4)
N—C1—C6123.1 (4)C1—C6—C7121.0 (3)
C2—C1—C6117.8 (3)O2—C7—O1121.9 (4)
C3—C2—C1121.4 (4)O2—C7—C6125.1 (4)
C3—C2—H2A119.3O1—C7—C6113.0 (3)
C1—C2—H2A119.3O1—C8—H8A109.5
C2—C3—C4120.7 (4)O1—C8—H8B109.5
C2—C3—H3A119.6H8A—C8—H8B109.5
C4—C3—H3A119.6O1—C8—H8C109.5
C5—C4—C3120.0 (4)H8A—C8—H8C109.5
C5—C4—Cl120.0 (3)H8B—C8—H8C109.5
C3—C4—Cl120.0 (3)
N—C1—C2—C3−179.8 (4)C2—C1—C6—C5−1.3 (5)
C6—C1—C2—C31.6 (6)N—C1—C6—C70.8 (5)
C1—C2—C3—C4−0.5 (6)C2—C1—C6—C7179.3 (4)
C2—C3—C4—C5−0.9 (6)C8—O1—C7—O20.9 (6)
C2—C3—C4—Cl179.3 (3)C8—O1—C7—C6−179.1 (4)
C3—C4—C5—C61.2 (6)C5—C6—C7—O2−175.1 (4)
Cl—C4—C5—C6−179.0 (3)C1—C6—C7—O24.3 (6)
C4—C5—C6—C10.0 (6)C5—C6—C7—O14.9 (5)
C4—C5—C6—C7179.3 (3)C1—C6—C7—O1−175.7 (3)
N—C1—C6—C5−179.8 (4)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N—H0A···O2i0.862.313.066 (5)147
N—H0B···O20.862.082.713 (5)129

Symmetry codes: (i) −x, y+1/2, −z+2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BQ2241).

References

  • Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19.
  • Dong, W. L. & Xu, J. Y. (2009). Chin. J. Chem.27, 579–586.
  • Enraf–Nonius (1989). CAD-4 EXPRESS Enraf–Nonius, Delft. The Netherlands.
  • Flack, H. D. (1983). Acta Cryst. A39, 876–881.
  • Harms, K. & Wocadlo, S. (1995). XCAD4 University of Marburg, Germany.
  • North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography