Methyl 2-amino-5-chloro­benzoate

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.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.005 Å
• R factor = 0.051
• wR factor = 0.160
• Data-to-parameter ratio = 15.1

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT340_ALERT_3_C Low Bond Precision on  C-C Bonds (x 1000) Ang ..          5

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           25.95
           From the CIF: _reflns_number_total               1663
           Count of symmetry unique reflns          886
           Completeness (_total/calc)            187.70%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured       777
           Fraction of Friedel pairs measured     0.877
           Are heavy atom types Z>Si present        yes
PLAT917_ALERT_2_G The FCF is likely NOT based on a BASF/TWIN Flack          !
PLAT180_ALERT_4_G Check Cell Rounding: # of Values Ending with 0 =          3
PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature        293 K
PLAT200_ALERT_1_G Check the Reported   _diffrn_ambient_temperature        293 K
PLAT720_ALERT_4_G Number of Unusual/Non-Standard Labels ..........          2

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   1 ALERT level C = Check and explain
   6 ALERT level G = General alerts; check

   2 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   3 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. 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.).

Related literature

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

S2. 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.

S3. 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 U_iso(H) = xU_eq(C,N), where x = 1.5 for methyl H and x = 1.2 for all other H atoms.

Computing details

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

	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

Crystal data

C8H8ClNO2	F(000) = 192
Mr = 185.60	Dx = 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) Å^3	Block, colourless
Z = 2	0.30 × 0.30 × 0.05 mm

Data collection

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

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.051	w = 1/[σ^2(Fo^2) + (0.1P)^2 + 0.190P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.160	(Δ/σ)max < 0.001
S = 1.01	Δρmax = 0.27 e Å^−3
1663 reflections	Δρmin = −0.19 e Å^−3
110 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc^2λ^3/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)

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 (Ų)

	x	y	z	Uiso*/Ueq
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 (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
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)

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)

D—H···A	D—H	H···A	D···A	D—H···A
N—H0A···O2^i	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.