Ethyl 3-carb­oxy-5-nitro­benzoate

Liu, Y.-L.; Zou, P.; Xie, M.-H.; Luo, S.-N.; He, Y.-J.

doi:10.1107/S160053680901558X

organic compounds

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ISSN: 2056-9890

Volume 65| Part 5| May 2009| Page o1174

doi:10.1107/S160053680901558X

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Ethyl 3-carboxy-5-nitrobenzoate

Ya-Ling Liu,^a Pei Zou,^a ^* Min-Hao Xie,^a Shi-Neng Luo ^a and Yong-Jun He ^a

^aJiangsu Institute of Nuclear Medicine, Wuxi 214063, People's Republic of China
^*Correspondence e-mail: liuyaling158@163.com

(Received 9 April 2009; accepted 27 April 2009; online 30 April 2009)

In the title compound, C₁₀H₉NO₆, the carboxy, ethoxycarbonyl and nitro groups form dihedral angles of 3.8 (1), 4.5 (1) and 164.8 (1)°, respectively, with the mean plane of the benzene ring. In the crystal structure, molecules lying about inversion centers are linked through O—H⋯O hydrogen bonds. C—H⋯O interactions are also present.

Related literature

The title compound is an important intermediate for the preparation of iodinated X-ray contrast media, such as iotalamic acid, ioxitalamic acid, and ioxilan, which are used clinically all over the world (Morin et al., 1987 ; Singh & Rathore, 1980 ; Stacul, 2001 ). For a related structure, see: Zou et al. (2009 ).

Experimental

Crystal data

C₁₀H₉NO₆
M_r = 239.18
Monoclinic, P 2₁ /n
a = 14.249 (3) Å
b = 4.6450 (9) Å
c = 16.536 (4) Å
β = 108.401 (3)°
V = 1038.5 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.13 mm⁻¹
T = 93 K
0.40 × 0.23 × 0.23 mm

Data collection

Rigaku SPIDER diffractometer
Absorption correction: none
6542 measured reflections
2355 independent reflections
1967 reflections with I > 2σ(I)
R_int = 0.024

Refinement

R[F² > 2σ(F²)] = 0.043
wR(F²) = 0.087
S = 0.99
2355 reflections
159 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.54 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O5—H5O⋯O6ⁱ	0.92 (3)	1.71 (3)	2.630 (2)	176.7 (17)
C6—H6⋯O2ⁱⁱ	0.95	2.35	3.280 (2)	165
C9—H9A⋯O6ⁱⁱⁱ	0.98	2.56	3.354 (3)	138
Symmetry codes: (i) -x+1, -y+2, -z+1; (ii) -x, -y, -z+1; (iii) $[-x+{\script{1\over 2}}, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Data collection: RAPID-AUTO (Rigaku, 2004 ); cell refinement: RAPID-AUTO; data reduction: RAPID-AUTO; 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: SHELXTL.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S160053680901558X/pv2153sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S160053680901558X/pv2153Isup2.hkl

checkCIF report

Comment top

The title compound is an important intermediate for the preparation of iodinated X-ray contrast media, such as iotalamic acid, ioxitalamic acid, and ioxilan, which are used clinically all over the world (Morin et al., 1987; Singh et al., 1980; Stacul, 2001). We report here the crystal structure of the title compound.

The crystal data show that the bond lengths and angles in the title compound (Fig. 1) are within expected ranges and agree well with the corresponding molecular dimensions reported for a similar compound (Zou et al., 2009). The carboxylic acid group (O5/C10/O6) attached at C3 and the ester group (O1/C7/O2) attached at C1 are nearly coplanar with the benzene ring (C1—C6) (dihedral angles of 3.8 (1) and 4.5 (1)°, respectively), while the nitro group (O3/N1/O4) attached at C5 forms a dihedral angle of 164.8 (1) ° with the benzene ring. In the cyrstal structure, the molecules lying about inversion centers are linked through O—H···O hydrogen bonds (Table 1).

Related literature top

The title compound is an important intermediate for the preparation of iodinated X-ray contrast media, such as iotalamic acid, ioxitalamic acid, and ioxilan, which are used clinically all over the world (Morin et al., 1987; Singh & Rathore, 1980; Stacul, 2001). For a related structure, see: Zou et al. (2009).

Experimental top

5-Nitroisophthalic acid (2.1 g, 0.01 mol) was dissolved in 1.5 M ethanolic hydrochloric acid solution (7.5 ml) at 323 K. The mixture was stirred at 323 K for 6 hr. Then sodium chloride (1.8 g, 0.03 mol) in water (20 ml) was added. An oily liquid separated and crystallized on cooling. The precipitate was suction filtered and washed with water until neutral. The solid was suspended in sodium bicarbonate (1.0 g, 0.01 mol) in water (10 ml) and the undissolved diester was filtered off. The filtrate was acidified with 1 M hydrochloric acid to a pH of 4. The precipitate was filtered and washed with cold water. The crude product was purified by recrystallization from ethanol (yield: 41%). Single crystals were grown by slow evaporation of a ethanol/water(v/v 1:1) solution: colourless prismatic crystals were formed after several days.

Computing details top

Data collection: RAPID-AUTO (Rigaku, 2004); cell refinement: RAPID-AUTO (Rigaku, 2004); data reduction: RAPID-AUTO (Rigaku, 2004); 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: SHELXTL (Sheldrick, 2008).

Figures top

Fig. 1. A view of the title compound with the atomic numbering scheme. Displacement ellipsoids were drawn at the 30% probability level.

Ethyl 3-carboxy-5-nitrobenzoate top

Crystal data top

C₁₀H₉NO₆	F(000) = 496
M_r = 239.18	D_x = 1.530 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 3010 reflections
a = 14.249 (3) Å	θ = 3.0–27.5°
b = 4.6450 (9) Å	µ = 0.13 mm⁻¹
c = 16.536 (4) Å	T = 93 K
β = 108.401 (3)°	Prism, colorless
V = 1038.5 (4) Å³	0.40 × 0.23 × 0.23 mm
Z = 4

Data collection top

Rigaku SPIDER diffractometer	1967 reflections with I > 2σ(I)
Radiation source: Rotating Anode	R_int = 0.024
Graphite monochromator	θ_max = 27.5°, θ_min = 3.0°
ω scans	h = −18→16
6542 measured reflections	k = −5→5
2355 independent reflections	l = −21→20

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)] = 0.043	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.087	H atoms treated by a mixture of independent and constrained refinement
S = 0.99	w = 1/[σ²(F_o²) + (0.018P)² + 0.9P] where P = (F_o² + 2F_c²)/3
2355 reflections	(Δ/σ)_max < 0.001
159 parameters	Δρ_max = 0.54 e Å⁻³
0 restraints	Δρ_min = −0.21 e Å⁻³

Crystal data top

C₁₀H₉NO₆	V = 1038.5 (4) Å³
M_r = 239.18	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 14.249 (3) Å	µ = 0.13 mm⁻¹
b = 4.6450 (9) Å	T = 93 K
c = 16.536 (4) Å	0.40 × 0.23 × 0.23 mm
β = 108.401 (3)°

Data collection top

Rigaku SPIDER diffractometer	1967 reflections with I > 2σ(I)
6542 measured reflections	R_int = 0.024
2355 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.043	0 restraints
wR(F²) = 0.087	H atoms treated by a mixture of independent and constrained refinement
S = 0.99	Δρ_max = 0.54 e Å⁻³
2355 reflections	Δρ_min = −0.21 e Å⁻³
159 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
O1	0.13780 (9)	0.1168 (3)	0.34968 (7)	0.0298 (3)
O2	0.03728 (8)	0.0126 (3)	0.42538 (7)	0.0276 (3)
O3	0.08919 (8)	0.5402 (3)	0.69486 (7)	0.0264 (3)
O4	0.18028 (8)	0.9233 (3)	0.71824 (7)	0.0254 (3)
O5	0.42632 (9)	1.0386 (3)	0.57257 (8)	0.0295 (3)
O6	0.41511 (9)	0.7677 (3)	0.45857 (8)	0.0372 (3)
N1	0.14799 (9)	0.7034 (3)	0.67837 (8)	0.0204 (3)
C1	0.16237 (11)	0.3639 (3)	0.47870 (9)	0.0191 (3)
C2	0.24472 (11)	0.5011 (4)	0.46934 (10)	0.0212 (3)
H2	0.2662	0.4570	0.4219	0.025*
C3	0.29609 (11)	0.7032 (4)	0.52916 (10)	0.0207 (3)
C4	0.26459 (11)	0.7719 (3)	0.59811 (10)	0.0202 (3)
H4	0.2985	0.9114	0.6389	0.024*
C5	0.18231 (11)	0.6311 (3)	0.60566 (9)	0.0186 (3)
C6	0.13113 (11)	0.4266 (3)	0.54859 (9)	0.0188 (3)
H6	0.0759	0.3304	0.5566	0.023*
C7	0.10519 (11)	0.1465 (4)	0.41636 (9)	0.0207 (3)
C8	0.08258 (14)	−0.0899 (5)	0.28589 (11)	0.0362 (5)
H8A	0.0140	−0.0217	0.2590	0.043*
H8B	0.0802	−0.2788	0.3129	0.043*
C9	0.13330 (17)	−0.1176 (6)	0.22150 (14)	0.0530 (6)
H9A	0.1328	0.0686	0.1935	0.064*
H9B	0.0991	−0.2611	0.1789	0.064*
H9C	0.2018	−0.1787	0.2491	0.064*
C10	0.38474 (12)	0.8391 (4)	0.51701 (10)	0.0242 (4)
H5O	0.4809 (18)	1.103 (5)	0.5597 (14)	0.064 (8)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0321 (6)	0.0351 (7)	0.0270 (6)	−0.0129 (6)	0.0161 (5)	−0.0098 (5)
O2	0.0262 (6)	0.0316 (7)	0.0261 (6)	−0.0117 (5)	0.0098 (5)	−0.0031 (5)
O3	0.0269 (6)	0.0273 (7)	0.0288 (6)	−0.0054 (5)	0.0143 (5)	0.0005 (5)
O4	0.0235 (6)	0.0245 (6)	0.0282 (6)	−0.0031 (5)	0.0080 (5)	−0.0077 (5)
O5	0.0227 (6)	0.0336 (7)	0.0357 (7)	−0.0122 (5)	0.0140 (5)	−0.0083 (6)
O6	0.0312 (7)	0.0485 (9)	0.0394 (7)	−0.0200 (6)	0.0218 (6)	−0.0161 (6)
N1	0.0171 (6)	0.0220 (7)	0.0220 (6)	0.0000 (5)	0.0057 (5)	0.0014 (6)
C1	0.0181 (7)	0.0184 (8)	0.0202 (7)	−0.0002 (6)	0.0052 (6)	0.0026 (6)
C2	0.0193 (7)	0.0234 (9)	0.0219 (7)	−0.0006 (6)	0.0079 (6)	0.0019 (7)
C3	0.0158 (7)	0.0212 (8)	0.0248 (7)	−0.0020 (6)	0.0060 (6)	0.0030 (7)
C4	0.0171 (7)	0.0189 (8)	0.0229 (7)	−0.0010 (6)	0.0040 (6)	0.0014 (6)
C5	0.0176 (7)	0.0194 (8)	0.0191 (7)	0.0018 (6)	0.0062 (6)	0.0032 (6)
C6	0.0155 (7)	0.0188 (8)	0.0219 (7)	−0.0003 (6)	0.0056 (6)	0.0051 (6)
C7	0.0200 (7)	0.0217 (9)	0.0209 (7)	−0.0010 (6)	0.0074 (6)	0.0024 (6)
C8	0.0397 (10)	0.0404 (12)	0.0311 (9)	−0.0145 (9)	0.0147 (8)	−0.0134 (8)
C9	0.0542 (14)	0.0675 (17)	0.0422 (12)	−0.0140 (12)	0.0224 (10)	−0.0208 (11)
C10	0.0197 (8)	0.0254 (9)	0.0272 (8)	−0.0044 (7)	0.0070 (6)	−0.0007 (7)

Geometric parameters (Å, º) top

O1—C7	1.3320 (19)	C2—H2	0.9500
O1—C8	1.460 (2)	C3—C4	1.388 (2)
O2—C7	1.1986 (19)	C3—C10	1.481 (2)
O3—N1	1.2230 (17)	C4—C5	1.382 (2)
O4—N1	1.2242 (17)	C4—H4	0.9500
O5—C10	1.308 (2)	C5—C6	1.375 (2)
O5—H5O	0.92 (3)	C6—H6	0.9500
O6—C10	1.223 (2)	C8—C9	1.469 (3)
N1—C5	1.4726 (19)	C8—H8A	0.9900
C1—C2	1.386 (2)	C8—H8B	0.9900
C1—C6	1.394 (2)	C9—H9A	0.9800
C1—C7	1.488 (2)	C9—H9B	0.9800
C2—C3	1.392 (2)	C9—H9C	0.9800

C7—O1—C8	114.65 (13)	C5—C6—H6	120.8
C10—O5—H5O	107.3 (15)	C1—C6—H6	120.8
O3—N1—O4	124.39 (13)	O2—C7—O1	123.74 (15)
O3—N1—C5	117.92 (13)	O2—C7—C1	123.56 (14)
O4—N1—C5	117.69 (13)	O1—C7—C1	112.70 (13)
C2—C1—C6	119.97 (14)	O1—C8—C9	107.75 (16)
C2—C1—C7	122.15 (14)	O1—C8—H8A	110.2
C6—C1—C7	117.88 (14)	C9—C8—H8A	110.2
C1—C2—C3	120.29 (14)	O1—C8—H8B	110.2
C1—C2—H2	119.9	C9—C8—H8B	110.2
C3—C2—H2	119.9	H8A—C8—H8B	108.5
C4—C3—C2	120.32 (14)	C8—C9—H9A	109.5
C4—C3—C10	121.61 (14)	C8—C9—H9B	109.5
C2—C3—C10	118.07 (14)	H9A—C9—H9B	109.5
C5—C4—C3	117.97 (14)	C8—C9—H9C	109.5
C5—C4—H4	121.0	H9A—C9—H9C	109.5
C3—C4—H4	121.0	H9B—C9—H9C	109.5
C6—C5—C4	123.11 (14)	O6—C10—O5	123.54 (15)
C6—C5—N1	118.49 (13)	O6—C10—C3	121.42 (15)
C4—C5—N1	118.40 (14)	O5—C10—C3	115.04 (14)
C5—C6—C1	118.31 (14)

C6—C1—C2—C3	−0.5 (2)	C2—C1—C6—C5	1.7 (2)
C7—C1—C2—C3	179.98 (14)	C7—C1—C6—C5	−178.76 (13)
C1—C2—C3—C4	−0.8 (2)	C8—O1—C7—O2	1.3 (2)
C1—C2—C3—C10	178.79 (14)	C8—O1—C7—C1	−178.77 (14)
C2—C3—C4—C5	0.9 (2)	C2—C1—C7—O2	175.54 (15)
C10—C3—C4—C5	−178.73 (14)	C6—C1—C7—O2	−4.0 (2)
C3—C4—C5—C6	0.4 (2)	C2—C1—C7—O1	−4.3 (2)
C3—C4—C5—N1	−179.71 (13)	C6—C1—C7—O1	176.11 (14)
O3—N1—C5—C6	14.8 (2)	C7—O1—C8—C9	−174.64 (17)
O4—N1—C5—C6	−165.20 (13)	C4—C3—C10—O6	176.32 (16)
O3—N1—C5—C4	−165.12 (14)	C2—C3—C10—O6	−3.3 (2)
O4—N1—C5—C4	14.9 (2)	C4—C3—C10—O5	−4.1 (2)
C4—C5—C6—C1	−1.7 (2)	C2—C3—C10—O5	176.29 (14)
N1—C5—C6—C1	178.44 (13)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O5—H5O···O6ⁱ	0.92 (3)	1.71 (3)	2.630 (2)	176.7 (17)
C6—H6···O2ⁱⁱ	0.95	2.35	3.280 (2)	165
C9—H9A···O6ⁱⁱⁱ	0.98	2.56	3.354 (3)	138

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

Experimental details

Crystal data
Chemical formula	C₁₀H₉NO₆
M_r	239.18
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	93
a, b, c (Å)	14.249 (3), 4.6450 (9), 16.536 (4)
β (°)	108.401 (3)
V (Å³)	1038.5 (4)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.13
Crystal size (mm)	0.40 × 0.23 × 0.23

Data collection
Diffractometer	Rigaku SPIDER diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	6542, 2355, 1967
R_int	0.024
(sin θ/λ)_max (Å⁻¹)	0.649

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.043, 0.087, 0.99
No. of reflections	2355
No. of parameters	159
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.54, −0.21

Computer programs: RAPID-AUTO (Rigaku, 2004), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O5—H5O···O6ⁱ	0.92 (3)	1.71 (3)	2.630 (2)	176.7 (17)
C6—H6···O2ⁱⁱ	0.9500	2.3500	3.280 (2)	165.00
C9—H9A···O6ⁱⁱⁱ	0.9800	2.5600	3.354 (3)	138.00

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

Acknowledgements

The authors acknowledge financial support from the Jiangsu Institute of Nuclear Medicine.

References

Morin, J. P., Boutelet, I., Toutain, H. & Fillastre, J. P. (1987). Pathol. Biol. 35, 1215–1220. CAS PubMed Web of Science Google Scholar
Rigaku (2004). RAPID-AUTO. Rigaku Corporation, Tokyo, Japan. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Singh, G. B. & Rathore, H. G. S. (1980). Indian Drug. Pharm. Ind. 15, 35–38. CAS Google Scholar
Stacul, F. (2001). Eur. Radiol. 11, 690–697. Web of Science CrossRef PubMed CAS Google Scholar
Zou, P., Xie, M.-H., Luo, S.-N., Liu, Y.-L. & Shen, Y.-J. (2009). Acta Cryst. E65, o335. Web of Science CSD CrossRef IUCr Journals Google Scholar