Methyl 5-chloro-2-nitro­benzoate

Liang, Y.-S.; Liu, B.-N.; Liu, M.; Liu, D.-K.

doi:10.1107/S1600536811044072

organic compounds

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ISSN: 2056-9890

Volume 67| Part 12| December 2011| Page o3139

https://doi.org/10.1107/S1600536811044072

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Methyl 5-chloro-2-nitrobenzoate

Yan-Shu Liang,^a ^* Bing-Ni Liu,^b Mo Liu ^b and Deng-Ke Liu ^b

^aTianjin University of Commerce, Tianjin 300134, People's Republic of China, and ^bTianjin Institute of Pharmaceutical Research, Tianjin, 300193, People's Republic of China
^*Correspondence e-mail: lyshu@tjcu.edu.cn

(Received 29 September 2011; accepted 24 October 2011; online 2 November 2011)

In the title compound, C₈H₆ClNO₄, the nitro and acetoxy groups attached to the benzene ring at neighbouring positions are twisted from its plane by 29.4 (1) and 49.7 (1)°, respectively. In the crystal, weak C—H⋯O hydrogen bonds link molecules into layers parallel to (101). The crystal packing exhibits short intermolecular C⋯O distances of 2.925 (3) Å.

Related literature

The title compound is an intermediate of the oral vasopressin V₂-receptor antagonist tolvaptan. For applications of tolvaptan, see: Nemerovski & Hutchinson (2010 ). For the synthesis of the title compound, see: Kondo et al. (1999 ). For a related structure, see: Liu et al. (2008 ).

Experimental

Crystal data

C₈H₆ClNO₄
M_r = 215.59
Monoclinic, P 2₁ /n
a = 4.2616 (9) Å
b = 22.470 (5) Å
c = 9.3894 (19) Å
β = 90.64 (3)°
V = 899.1 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.41 mm⁻¹
T = 113 K
0.16 × 0.14 × 0.12 mm

Data collection

Rigaku Saturn diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005 ) T_min = 0.937, T_max = 0.952
5007 measured reflections
1564 independent reflections
1400 reflections with I > 2σ(I)
R_int = 0.031

Refinement

R[F² > 2σ(F²)] = 0.041
wR(F²) = 0.116
S = 1.07
1564 reflections
128 parameters
H-atom parameters constrained
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.27 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C2—H2⋯O1ⁱ	0.93	2.53	3.206 (3)	130
C8—H8B⋯O3ⁱⁱ	0.96	2.47	3.200 (3)	132
Symmetry codes: (i) -x+1, -y, -z+1; (ii) $[x-{\script{1\over 2}}, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ .

Data collection: CrystalClear (Rigaku/MSC, 2005); cell refinement: CrystalClear; data reduction: CrystalClear; 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: https://doi.org/10.1107/S1600536811044072/cv5162sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536811044072/cv5162Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S1600536811044072/cv5162Isup3.cdx

Supporting information file. DOI: https://doi.org/10.1107/S1600536811044072/cv5162Isup4.cml

checkCIF report

Comment top

Tolvaptan is an oral nonpeptide selective vasopressin V₂-receptor antagonist indicated for the treatment of clinically relevant hypervolemic or euvolemic hyponatremia associated with heart failure, cirrhosis, or syndrome of inappropriate antidiuretic hormone (Nemerovski et al., 2010). Now, we present the crystal structure of the title compound (I) (Kondo et al., 1999), an intermediate of Tolvaptan.

In (I) (Fig. 1), all bond lengths and angles are normal and correspond to those observed in the analougs (Liu et al., 2008). The acetoxy and nitro groups attached to the benzene ring at neighbouring positions are twisted from its plane at 49.7 (1) and 29.4 (1)°, respectively. In the crystal structure, weak C—H···O interactions (Table 1) link molecules into layers parallel to (101) plane. Short intermolecular C···O distances of 2.925 (3) Å observed in the structure.

Related literature top

The title compound is an intermediate of the oral vasopressin V₂-receptor antagonist tolvaptan. For applications of tolvaptan, see: Nemerovski & Hutchinson (2010). For the synthesis of the title compound, see: Kondo et al. (1999). For a related structure, see: Liu et al. (2008).

Experimental top

To a stirred solution of the 5-chloro-2-nitrobenzoic acid (10 g, 50 mmol) in acetone(60 ml) was added K₂CO₃ (10.3 g, 74 mmol) and Me₂SO₄ (6.2 ml, 64.7 mmol). The mixture was heated at reflux for 30 min. The reaction mixture was then poured into an ice-water bath and extracted with ethyl acetate. The organic layer was separated and dried over MgSO₄. then the filtrate was concentrate under reduced pressure to afford the methyl ester as a white solid. Pure compound (I) was obstained by crystallizing from methanol. Crystals of (I) suitable for X-ray diffraction were obstained by slow evaporation of an methanol solution.

Structure description top

The title compound is an intermediate of the oral vasopressin V₂-receptor antagonist tolvaptan. For applications of tolvaptan, see: Nemerovski & Hutchinson (2010). For the synthesis of the title compound, see: Kondo et al. (1999). For a related structure, see: Liu et al. (2008).

Computing details top

Data collection: CrystalClear (Rigaku/MSC, 2005); cell refinement: CrystalClear (Rigaku/MSC, 2005); data reduction: CrystalClear (Rigaku/MSC, 2005); 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. The molecular structure of (I), with the atom-numbering scheme and 50% probability displacement ellipsoids.

Methyl 5-chloro-2-nitrobenzoate top

Crystal data top

C₈H₆ClNO₄	F(000) = 440
M_r = 215.59	D_x = 1.593 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 2662 reflections
a = 4.2616 (9) Å	θ = 1.8–27.5°
b = 22.470 (5) Å	µ = 0.41 mm⁻¹
c = 9.3894 (19) Å	T = 113 K
β = 90.64 (3)°	Prism, colorless
V = 899.1 (3) Å³	0.16 × 0.14 × 0.12 mm
Z = 4

Data collection top

Rigaku Saturn diffractometer	1564 independent reflections
Radiation source: rotating anode	1400 reflections with I > 2σ(I)
Confocal monochromator	R_int = 0.031
ω scans	θ_max = 25.0°, θ_min = 2.4°
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005)	h = −4→5
T_min = 0.937, T_max = 0.952	k = −26→20
5007 measured reflections	l = −11→11

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)] = 0.041	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.116	H-atom parameters constrained
S = 1.07	w = 1/[σ²(F_o²) + (0.0708P)² + 0.3934P] where P = (F_o² + 2F_c²)/3
1564 reflections	(Δ/σ)_max = 0.001
128 parameters	Δρ_max = 0.27 e Å⁻³
0 restraints	Δρ_min = −0.27 e Å⁻³

Crystal data top

C₈H₆ClNO₄	V = 899.1 (3) Å³
M_r = 215.59	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 4.2616 (9) Å	µ = 0.41 mm⁻¹
b = 22.470 (5) Å	T = 113 K
c = 9.3894 (19) Å	0.16 × 0.14 × 0.12 mm
β = 90.64 (3)°

Data collection top

Rigaku Saturn diffractometer	1564 independent reflections
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005)	1400 reflections with I > 2σ(I)
T_min = 0.937, T_max = 0.952	R_int = 0.031
5007 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.041	0 restraints
wR(F²) = 0.116	H-atom parameters constrained
S = 1.07	Δρ_max = 0.27 e Å⁻³
1564 reflections	Δρ_min = −0.27 e Å⁻³
128 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
Cl1	0.83432 (12)	0.09111 (2)	1.09984 (5)	0.0272 (2)
O1	0.1416 (4)	0.05968 (8)	0.42100 (17)	0.0423 (5)
O2	−0.1876 (4)	0.12282 (9)	0.48951 (17)	0.0409 (5)
O3	0.1575 (4)	0.22747 (7)	0.57507 (16)	0.0364 (4)
O4	−0.0357 (3)	0.22861 (6)	0.78230 (15)	0.0263 (4)
N1	0.0553 (5)	0.09256 (8)	0.51178 (19)	0.0282 (5)
C1	0.2555 (5)	0.09452 (9)	0.6557 (2)	0.0224 (5)
C2	0.4194 (5)	0.04329 (9)	0.7038 (2)	0.0273 (5)
H2	0.4148	0.0092	0.6478	0.033*
C3	0.6002 (5)	0.04214 (9)	0.8420 (2)	0.0263 (5)
H3	0.7041	0.0077	0.8707	0.032*
C4	0.6111 (5)	0.09270 (8)	0.9265 (2)	0.0215 (5)
C5	0.4463 (5)	0.14420 (9)	0.8781 (2)	0.0224 (5)
H5	0.4519	0.1783	0.9342	0.027*
C6	0.2642 (5)	0.14566 (9)	0.7406 (2)	0.0218 (5)
C7	0.1199 (5)	0.20438 (9)	0.6857 (2)	0.0228 (5)
C8	−0.1662 (6)	0.28749 (10)	0.7466 (2)	0.0323 (5)
H8A	0.0017	0.3157	0.7373	0.049*
H8B	−0.3039	0.3001	0.8209	0.049*
H8C	−0.2814	0.2850	0.6584	0.049*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0369 (4)	0.0243 (3)	0.0204 (3)	0.0011 (2)	−0.0024 (2)	0.00056 (18)
O1	0.0641 (13)	0.0388 (10)	0.0241 (9)	0.0017 (8)	0.0011 (8)	−0.0105 (7)
O2	0.0322 (10)	0.0596 (12)	0.0308 (9)	0.0044 (8)	0.0003 (7)	0.0013 (8)
O3	0.0481 (10)	0.0359 (9)	0.0256 (9)	0.0124 (7)	0.0201 (7)	0.0125 (7)
O4	0.0334 (9)	0.0244 (8)	0.0215 (8)	0.0032 (6)	0.0139 (6)	0.0031 (6)
N1	0.0335 (11)	0.0305 (10)	0.0206 (10)	−0.0064 (8)	0.0023 (8)	0.0002 (8)
C1	0.0231 (11)	0.0270 (11)	0.0174 (11)	−0.0047 (8)	0.0048 (8)	−0.0011 (8)
C2	0.0352 (12)	0.0223 (10)	0.0246 (11)	−0.0058 (9)	0.0087 (9)	−0.0063 (8)
C3	0.0331 (12)	0.0209 (10)	0.0252 (12)	−0.0008 (9)	0.0071 (9)	0.0024 (8)
C4	0.0255 (11)	0.0217 (10)	0.0176 (10)	−0.0033 (8)	0.0055 (8)	0.0018 (8)
C5	0.0280 (11)	0.0215 (10)	0.0178 (10)	−0.0035 (8)	0.0100 (8)	−0.0003 (8)
C6	0.0229 (11)	0.0252 (10)	0.0175 (10)	−0.0030 (8)	0.0099 (8)	0.0020 (8)
C7	0.0242 (10)	0.0258 (10)	0.0186 (11)	−0.0017 (8)	0.0049 (8)	−0.0004 (8)
C8	0.0416 (14)	0.0250 (11)	0.0307 (13)	0.0076 (10)	0.0123 (10)	0.0038 (9)

Geometric parameters (Å, º) top

Cl1—C4	1.876 (2)	C2—H2	0.9300
O1—N1	1.189 (2)	C3—C4	1.386 (3)
O2—N1	1.254 (3)	C3—H3	0.9300
O3—C7	1.174 (2)	C4—C5	1.425 (3)
O4—C7	1.254 (2)	C5—C6	1.500 (3)
O4—C8	1.472 (3)	C5—H5	0.9300
N1—C1	1.590 (3)	C6—C7	1.542 (3)
C1—C6	1.399 (3)	C8—H8A	0.9600
C1—C2	1.418 (3)	C8—H8B	0.9600
C2—C3	1.502 (3)	C8—H8C	0.9600

C7—O4—C8	115.29 (16)	C4—C5—C6	122.73 (18)
O1—N1—O2	118.6 (2)	C4—C5—H5	118.6
O1—N1—C1	117.30 (18)	C6—C5—H5	118.6
O2—N1—C1	124.10 (17)	C1—C6—C5	118.89 (18)
C6—C1—C2	118.4 (2)	C1—C6—C7	120.30 (18)
C6—C1—N1	121.16 (18)	C5—C6—C7	120.47 (17)
C2—C1—N1	120.40 (17)	O3—C7—O4	121.8 (2)
C1—C2—C3	122.38 (18)	O3—C7—C6	128.04 (18)
C1—C2—H2	118.8	O4—C7—C6	110.01 (16)
C3—C2—H2	118.8	O4—C8—H8A	109.5
C4—C3—C2	119.62 (19)	O4—C8—H8B	109.5
C4—C3—H3	120.2	H8A—C8—H8B	109.5
C2—C3—H3	120.2	O4—C8—H8C	109.5
C3—C4—C5	118.0 (2)	H8A—C8—H8C	109.5
C3—C4—Cl1	119.63 (16)	H8B—C8—H8C	109.5
C5—C4—Cl1	122.36 (15)

O1—N1—C1—C6	152.58 (19)	N1—C1—C6—C5	177.54 (15)
O2—N1—C1—C6	−28.3 (3)	C2—C1—C6—C7	173.45 (17)
O1—N1—C1—C2	−30.1 (3)	N1—C1—C6—C7	−9.2 (3)
O2—N1—C1—C2	149.0 (2)	C4—C5—C6—C1	−0.1 (3)
C6—C1—C2—C3	0.1 (3)	C4—C5—C6—C7	−173.43 (18)
N1—C1—C2—C3	−177.31 (16)	C8—O4—C7—O3	0.0 (3)
C1—C2—C3—C4	−0.4 (3)	C8—O4—C7—C6	175.57 (17)
C2—C3—C4—C5	0.4 (3)	C1—C6—C7—O3	−48.6 (3)
C2—C3—C4—Cl1	179.53 (14)	C5—C6—C7—O3	124.6 (2)
C3—C4—C5—C6	−0.1 (3)	C1—C6—C7—O4	136.20 (19)
Cl1—C4—C5—C6	−179.27 (14)	C5—C6—C7—O4	−50.6 (2)
C2—C1—C6—C5	0.2 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2···O1ⁱ	0.93	2.53	3.206 (3)	130
C8—H8B···O3ⁱⁱ	0.96	2.47	3.200 (3)	132

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

Experimental details

Crystal data
Chemical formula	C₈H₆ClNO₄
M_r	215.59
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	113
a, b, c (Å)	4.2616 (9), 22.470 (5), 9.3894 (19)
β (°)	90.64 (3)
V (Å³)	899.1 (3)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.41
Crystal size (mm)	0.16 × 0.14 × 0.12

Data collection
Diffractometer	Rigaku Saturn
Absorption correction	Multi-scan (CrystalClear; Rigaku/MSC, 2005)
T_min, T_max	0.937, 0.952
No. of measured, independent and observed [I > 2σ(I)] reflections	5007, 1564, 1400
R_int	0.031
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.041, 0.116, 1.07
No. of reflections	1564
No. of parameters	128
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.27, −0.27

Computer programs: CrystalClear (Rigaku/MSC, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2···O1ⁱ	0.93	2.53	3.206 (3)	129.6
C8—H8B···O3ⁱⁱ	0.96	2.47	3.200 (3)	132.4

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

Acknowledgements

The authors thank Mr Hai-Bin Song of Nankai University for his kind assistance with the X-ray structure determination and for helpful suggestions.

References

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