Methyl 2-amino-5-chloro­benzoate

Shi, Y.-B.; Xia, S.; He, F.-F.; Wang, H.-B.

doi:10.1107/S1600536810042510

organic compounds

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Volume 66| Part 11| November 2010| Page o3025

https://doi.org/10.1107/S1600536810042510

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Methyl 2-amino-5-chlorobenzoate

Ya-Bin Shi,^a,^b Song Xia,^a,^b Fei-Fei He ^a,^b and Hai-Bo Wang ^b ^*

^aCollege of Science, Nanjing University of Technology, Xinmofan Road No. 5 Nanjing, Nanjing 210009, People's Republic of China, and ^bCollege of Food Science and Light Industry, Nanjing University of Technology, Xinmofan Road No. 5 Nanjing, Nanjing 210009, People's Republic of China
^*Correspondence e-mail: wanghaibo@njut.edu.cn

(Received 12 October 2010; accepted 20 October 2010; online 31 October 2010)

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 ). For bond-length data, see: Allen et al. (1987 ).

Experimental

Crystal data

C₈H₈ClNO₂
M_r = 185.60
Monoclinic, P 2₁
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 ) 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[F² > 2σ(F²)] = 0.051
wR(F²) = 0.160
S = 1.01
1663 reflections
110 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.19 e Å⁻³
Absolute structure: Flack (1983 ), 777 Friedel pairs
Flack parameter: 0.30 (14)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N—H0A⋯O2ⁱ	0.86	2.31	3.066 (5)	147
N—H0B⋯O2	0.86	2.08	2.713 (5)	129
Symmetry code: (i) $[-x, y+{\script{1\over 2}}, -z+2]$ .

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

Supporting information

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

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810042510/bq2241Isup2.hkl

checkCIF report

Comment top

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.).

Related literature top

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

Experimental top

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.

Structure description top

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

Computing details top

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

Figures top

	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.

Methyl 2-amino-5-chlorobenzoate top

Crystal data top

C₈H₈ClNO₂	F(000) = 192
M_r = 185.60	D_x = 1.444 Mg m⁻³
Monoclinic, P2₁	Melting point: 343 K
Hall symbol: P 2yb	Mo Kα radiation, λ = 0.71073 Å
a = 3.9480 (8) Å	Cell parameters from 25 reflections
b = 9.0230 (18) Å	θ = 10–14°
c = 12.018 (2) Å	µ = 0.40 mm⁻¹
β = 94.10 (3)°	T = 293 K
V = 427.02 (15) Å³	Block, colourless
Z = 2	0.30 × 0.30 × 0.05 mm

Data collection top

Enraf–Nonius CAD-4 diffractometer	1437 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.035
Graphite monochromator	θ_max = 26.0°, θ_min = 1.7°
ω/2θ scans	h = 0→4
Absorption correction: ψ scan (North et al., 1968)	k = −11→11
T_min = 0.889, T_max = 0.980	l = −14→14
1911 measured reflections	3 standard reflections every 200 reflections
1663 independent reflections	intensity decay: 1%

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.051	w = 1/[σ²(F_o²) + (0.1P)² + 0.190P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.160	(Δ/σ)_max < 0.001
S = 1.01	Δρ_max = 0.27 e Å⁻³
1663 reflections	Δρ_min = −0.19 e Å⁻³
110 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
1 restraint	Extinction coefficient: 0.103 (19)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), 777 Friedel pairs
Secondary atom site location: difference Fourier map	Absolute structure parameter: 0.30 (14)

Crystal data top

C₈H₈ClNO₂	V = 427.02 (15) Å³
M_r = 185.60	Z = 2
Monoclinic, P2₁	Mo Kα radiation
a = 3.9480 (8) Å	µ = 0.40 mm⁻¹
b = 9.0230 (18) Å	T = 293 K
c = 12.018 (2) Å	0.30 × 0.30 × 0.05 mm
β = 94.10 (3)°

Data collection top

Enraf–Nonius CAD-4 diffractometer	1437 reflections with I > 2σ(I)
Absorption correction: ψ scan (North et al., 1968)	R_int = 0.035
T_min = 0.889, T_max = 0.980	3 standard reflections every 200 reflections
1911 measured reflections	intensity decay: 1%
1663 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.051	H-atom parameters constrained
wR(F²) = 0.160	Δρ_max = 0.27 e Å⁻³
S = 1.01	Δρ_min = −0.19 e Å⁻³
1663 reflections	Absolute structure: Flack (1983), 777 Friedel pairs
110 parameters	Absolute structure parameter: 0.30 (14)
1 restraint

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

	x	y	z	U_iso*/U_eq
Cl	0.5983 (3)	0.76879 (13)	0.57288 (9)	0.0669 (4)
N	0.1559 (10)	0.5027 (4)	0.9873 (3)	0.0566 (10)
H0A	0.1791	0.5545	1.0474	0.068*
H0B	0.0700	0.4152	0.9888	0.068*
O1	0.1109 (8)	0.2663 (4)	0.6830 (2)	0.0570 (7)
C1	0.2559 (10)	0.5595 (4)	0.8894 (3)	0.0416 (8)
O2	−0.0279 (9)	0.2648 (4)	0.8588 (2)	0.0664 (8)
C2	0.3960 (10)	0.7029 (4)	0.8887 (4)	0.0471 (9)
H2A	0.4190	0.7567	0.9548	0.057*
C3	0.4982 (9)	0.7643 (5)	0.7937 (3)	0.0484 (8)
H3A	0.5884	0.8595	0.7954	0.058*
C4	0.4699 (10)	0.6870 (4)	0.6945 (3)	0.0459 (9)
C5	0.3416 (10)	0.5457 (4)	0.6914 (3)	0.0437 (9)
H5A	0.3266	0.4932	0.6246	0.052*
C6	0.2327 (9)	0.4797 (4)	0.7884 (3)	0.0410 (8)
C7	0.0929 (10)	0.3288 (4)	0.7827 (3)	0.0425 (8)
C8	−0.0251 (14)	0.1186 (5)	0.6689 (4)	0.0650 (13)
H8A	0.0020	0.0853	0.5941	0.097*
H8B	−0.2619	0.1192	0.6822	0.097*
H8C	0.0942	0.0528	0.7208	0.097*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl	0.0859 (8)	0.0590 (6)	0.0578 (6)	−0.0183 (6)	0.0195 (5)	0.0133 (5)
N	0.082 (3)	0.049 (2)	0.0405 (18)	0.0089 (18)	0.0160 (17)	0.0031 (16)
O1	0.0802 (18)	0.0415 (13)	0.0503 (14)	−0.0169 (17)	0.0130 (13)	−0.0067 (15)
C1	0.048 (2)	0.0374 (18)	0.0394 (19)	0.0079 (16)	0.0049 (16)	0.0026 (15)
O2	0.099 (2)	0.0470 (16)	0.0564 (16)	−0.009 (2)	0.0251 (15)	0.0092 (17)
C2	0.052 (2)	0.042 (2)	0.048 (2)	0.0045 (17)	0.0046 (16)	−0.0069 (17)
C3	0.050 (2)	0.0359 (17)	0.059 (2)	−0.002 (2)	0.0056 (16)	−0.002 (2)
C4	0.048 (2)	0.043 (2)	0.048 (2)	−0.0020 (18)	0.0067 (16)	0.0090 (17)
C5	0.050 (2)	0.041 (2)	0.041 (2)	−0.0016 (16)	0.0110 (16)	−0.0016 (16)
C6	0.0412 (19)	0.0360 (18)	0.046 (2)	0.0028 (15)	0.0068 (15)	0.0057 (15)
C7	0.048 (2)	0.0347 (17)	0.045 (2)	0.0013 (16)	0.0053 (16)	0.0034 (15)
C8	0.080 (3)	0.042 (2)	0.073 (3)	−0.018 (2)	0.007 (3)	−0.008 (2)

Geometric parameters (Å, º) top

Cl—C4	1.744 (4)	C2—H2A	0.9300
N—C1	1.367 (5)	C3—C4	1.379 (6)
N—H0A	0.8600	C3—H3A	0.9300
N—H0B	0.8600	C4—C5	1.372 (5)
O1—C7	1.330 (5)	C5—C6	1.403 (5)
O1—C8	1.443 (5)	C5—H5A	0.9300
C1—C2	1.408 (6)	C6—C7	1.469 (5)
C1—C6	1.409 (5)	C8—H8A	0.9600
O2—C7	1.208 (5)	C8—H8B	0.9600
C2—C3	1.357 (6)	C8—H8C	0.9600

C1—N—H0A	120.0	C4—C5—C6	120.4 (4)
C1—N—H0B	120.0	C4—C5—H5A	119.8
H0A—N—H0B	120.0	C6—C5—H5A	119.8
C7—O1—C8	117.0 (3)	C5—C6—C1	119.6 (3)
N—C1—C2	119.1 (4)	C5—C6—C7	119.4 (4)
N—C1—C6	123.1 (4)	C1—C6—C7	121.0 (3)
C2—C1—C6	117.8 (3)	O2—C7—O1	121.9 (4)
C3—C2—C1	121.4 (4)	O2—C7—C6	125.1 (4)
C3—C2—H2A	119.3	O1—C7—C6	113.0 (3)
C1—C2—H2A	119.3	O1—C8—H8A	109.5
C2—C3—C4	120.7 (4)	O1—C8—H8B	109.5
C2—C3—H3A	119.6	H8A—C8—H8B	109.5
C4—C3—H3A	119.6	O1—C8—H8C	109.5
C5—C4—C3	120.0 (4)	H8A—C8—H8C	109.5
C5—C4—Cl	120.0 (3)	H8B—C8—H8C	109.5
C3—C4—Cl	120.0 (3)

N—C1—C2—C3	−179.8 (4)	C2—C1—C6—C5	−1.3 (5)
C6—C1—C2—C3	1.6 (6)	N—C1—C6—C7	0.8 (5)
C1—C2—C3—C4	−0.5 (6)	C2—C1—C6—C7	179.3 (4)
C2—C3—C4—C5	−0.9 (6)	C8—O1—C7—O2	0.9 (6)
C2—C3—C4—Cl	179.3 (3)	C8—O1—C7—C6	−179.1 (4)
C3—C4—C5—C6	1.2 (6)	C5—C6—C7—O2	−175.1 (4)
Cl—C4—C5—C6	−179.0 (3)	C1—C6—C7—O2	4.3 (6)
C4—C5—C6—C1	0.0 (6)	C5—C6—C7—O1	4.9 (5)
C4—C5—C6—C7	179.3 (3)	C1—C6—C7—O1	−175.7 (3)
N—C1—C6—C5	−179.8 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N—H0A···O2ⁱ	0.86	2.31	3.066 (5)	147
N—H0B···O2	0.86	2.08	2.713 (5)	129

Symmetry code: (i) −x, y+1/2, −z+2.

Experimental details

Crystal data
Chemical formula	C₈H₈ClNO₂
M_r	185.60
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	293
a, b, c (Å)	3.9480 (8), 9.0230 (18), 12.018 (2)
β (°)	94.10 (3)
V (Å³)	427.02 (15)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.40
Crystal size (mm)	0.30 × 0.30 × 0.05

Data collection
Diffractometer	Enraf–Nonius CAD-4
Absorption correction	ψ scan (North et al., 1968)
T_min, T_max	0.889, 0.980
No. of measured, independent and observed [I > 2σ(I)] reflections	1911, 1663, 1437
R_int	0.035
(sin θ/λ)_max (Å⁻¹)	0.616

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.051, 0.160, 1.01
No. of reflections	1663
No. of parameters	110
No. of restraints	1
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.27, −0.19
Absolute structure	Flack (1983), 777 Friedel pairs
Absolute structure parameter	0.30 (14)

Computer programs: CAD-4 EXPRESS (Enraf–Nonius, 1989), XCAD4 (Harms & Wocadlo, 1995), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008), PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N—H0A···O2ⁱ	0.86	2.31	3.066 (5)	147
N—H0B···O2	0.86	2.08	2.713 (5)	129

Symmetry code: (i) −x, y+1/2, −z+2.

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. CSD CrossRef Web of Science Google Scholar
Dong, W. L. & Xu, J. Y. (2009). Chin. J. Chem. 27, 579–586. CSD CrossRef CAS Google Scholar
Enraf–Nonius (1989). CAD-4 EXPRESS. Enraf–Nonius, Delft. The Netherlands. Google Scholar
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany. Google Scholar
North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359. CrossRef IUCr Journals Web of Science Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar

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CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 66| Part 11| November 2010| Page o3025

https://doi.org/10.1107/S1600536810042510

Open

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