Methyl 6-chloro­nicotinate

Xu, Y.; Yang, L.-L.; Yang, S.-Y.; Liu, J.

doi:10.1107/S1600536811053517

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 68| Part 1| January 2012| Page o162

doi:10.1107/S1600536811053517

Open

access

Methyl 6-chloronicotinate

Yong Xu,^a Ling-Ling Yang,^b Sheng-Yong Yang ^a and Jie Liu ^a ^*

^aState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People's Republic of China, and ^bDepartment of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu 610065, People's Republic of China
^*Correspondence e-mail: liujie2011@scu.edu.cn

(Received 1 December 2011; accepted 12 December 2011; online 17 December 2011)

The molecule of the title compound, C₇H₆ClNO₂, is almost planar, with a dihedral angle of 3.34 (14)° between the COOMe group and the aromatic ring. In the crystal, the molecules are arranged into (1 $[\overline{1}]$ 2) layers by C—H⋯N hydrogen bonds and there are π–π stacking interactions between the aromatic rings in adjacent layers [centroid–centroid distance 3.8721 (4) Å]

Related literature

For background to the synthesis of methyl 6-chloronicotinate, see: González et al. (2009 ); Rekha et al. (2009 ). For a related structure, see: Ma & Liu (2008 ).

Experimental

Crystal data

C₇H₆ClNO₂
M_r = 171.58
Triclinic, $[P \overline 1]$
a = 3.8721 (4) Å
b = 5.8068 (6) Å
c = 17.3721 (18) Å
α = 95.563 (9)°
β = 94.918 (8)°
γ = 104.657 (9)°
V = 373.64 (7) Å³
Z = 2
Mo Kα radiation
μ = 0.45 mm⁻¹
T = 293 K
0.30 × 0.30 × 0.12 mm

Data collection

Oxford Diffraction Xcalibur E diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011 ) T_min = 0.037, T_max = 1.000
3068 measured reflections
1527 independent reflections
855 reflections with I > 2σ(I)
R_int = 0.029

Refinement

R[F² > 2σ(F²)] = 0.055
wR(F²) = 0.119
S = 0.99
1527 reflections
101 parameters
H-atom parameters constrained
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C3—H3⋯N1ⁱ	0.93	2.59	3.440 (4)	151
Symmetry code: (i) x-1, y-1, z.

Data collection: CrysAlis PRO (Agilent, 2011); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009 ) and Mercury (Macrae et al., 2006 ); software used to prepare material for publication: OLEX2.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811053517/gk2439sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811053517/gk2439Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536811053517/gk2439Isup3.cml

checkCIF report

Comment top

The title compound is one of the key intermediates in our synthetic investigations of GPCR(G-protein coupled receptor) modulators. We have synthesized the title compound and here we report its crystal structure.

As shown in Fig.1, the molecule is nearly planar, the dihedral angle formed by the pyridine ring and the ester group (C6/C7/O1/O2) being 3.34 (14)°. Weak C—H···O and C—H···N hydrogen bonds are present in the crystal structure linking molecules into (1 -1 2) layers. There are also π-π stacking interactions between the aromatic rings in adjacent layers [centroid-centroid distance 3.8721 (4) Å].

Related literature top

For background to the synthesis of methyl 6-chloronicotinate, see: González et al. (2009); Rekha et al. (2009). For a related structure, see: Ma & Liu (2008).

Experimental top

The title compound was prepared by the following method. A mixture of 6-chloronicotinic acid (5.67 g, 0.036 mol), dimethyl carbonate (10.95 mL, 0.131 mol) and concentrated H₂SO₄ (2.72 mL, 0.049 mol) was refluxed for 17 h. Then aqueous NaHCO₃ solution (8.6 g in 86 mL water) was added, extracted with dichloromethane (150 mL), dried (Na₂SO₄), filtered and evaporated under reduced pressure to afford the title compound. Crystals suitable for X-ray analysis were obtained by slow evaporation from dichloromethane solution at room temperature over a period of one week.

Computing details top

Data collection: CrysAlis PRO (Agilent, 2011); cell refinement: CrysAlis PRO (Agilent, 2011); data reduction: CrysAlis PRO (Agilent, 2011); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009) and Mercury (Macrae et al., 2006); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Figures top

	Fig. 1. The molecular structure of the title compound with displacement ellipsoids drawn at the 30% probability level.
	Fig. 2. A packing diagram of the title compound. Intermolecular interactions are shown as dashed lines in blue.

methyl 6-chloropyridine-3-carboxylate top

Crystal data top

C₇H₆ClNO₂	Z = 2
M_r = 171.58	F(000) = 176
Triclinic, P1	D_x = 1.525 Mg m⁻³
a = 3.8721 (4) Å	Mo Kα radiation, λ = 0.7107 Å
b = 5.8068 (6) Å	Cell parameters from 741 reflections
c = 17.3721 (18) Å	θ = 3.6–26.3°
α = 95.563 (9)°	µ = 0.45 mm⁻¹
β = 94.918 (8)°	T = 293 K
γ = 104.657 (9)°	Block, colourless
V = 373.64 (7) Å³	0.30 × 0.30 × 0.12 mm

Data collection top

Oxford Diffraction Xcalibur E diffractometer	1527 independent reflections
Radiation source: Enhance (Mo) X-ray Source	855 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.029
Detector resolution: 16.0874 pixels mm^-1	θ_max = 26.4°, θ_min = 3.6°
ω scans	h = −4→4
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011)	k = −7→7
T_min = 0.037, T_max = 1.000	l = −21→21
3068 measured reflections

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)] = 0.055	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.119	H-atom parameters constrained
S = 0.99	w = 1/[σ²(F_o²) + (0.041P)²] where P = (F_o² + 2F_c²)/3
1527 reflections	(Δ/σ)_max < 0.001
101 parameters	Δρ_max = 0.23 e Å⁻³
0 restraints	Δρ_min = −0.18 e Å⁻³

Crystal data top

C₇H₆ClNO₂	γ = 104.657 (9)°
M_r = 171.58	V = 373.64 (7) Å³
Triclinic, P1	Z = 2
a = 3.8721 (4) Å	Mo Kα radiation
b = 5.8068 (6) Å	µ = 0.45 mm⁻¹
c = 17.3721 (18) Å	T = 293 K
α = 95.563 (9)°	0.30 × 0.30 × 0.12 mm
β = 94.918 (8)°

Data collection top

Oxford Diffraction Xcalibur E diffractometer	1527 independent reflections
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011)	855 reflections with I > 2σ(I)
T_min = 0.037, T_max = 1.000	R_int = 0.029
3068 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.055	0 restraints
wR(F²) = 0.119	H-atom parameters constrained
S = 0.99	Δρ_max = 0.23 e Å⁻³
1527 reflections	Δρ_min = −0.18 e Å⁻³
101 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	0.3480 (2)	1.23478 (16)	0.44450 (4)	0.0710 (4)
O1	0.4875 (6)	0.7116 (4)	0.10003 (12)	0.0728 (8)
O2	0.1351 (5)	0.3994 (4)	0.14496 (10)	0.0521 (6)
N1	0.5039 (6)	1.1467 (5)	0.30475 (15)	0.0529 (7)
C1	0.3350 (8)	1.0448 (6)	0.36075 (16)	0.0452 (8)
C2	0.1561 (7)	0.8050 (6)	0.35567 (17)	0.0480 (8)
H2	0.0435	0.7421	0.3971	0.058*
C3	0.1498 (7)	0.6630 (6)	0.28773 (15)	0.0443 (8)
H3	0.0331	0.5003	0.2823	0.053*
C4	0.3182 (7)	0.7630 (5)	0.22726 (15)	0.0399 (7)
C5	0.4935 (7)	1.0035 (5)	0.23934 (17)	0.0484 (8)
H5	0.6125	1.0704	0.1993	0.058*
C6	0.3266 (8)	0.6273 (6)	0.15097 (18)	0.0464 (8)
C7	0.1289 (8)	0.2550 (6)	0.07211 (16)	0.0618 (10)
H7A	−0.0050	0.3080	0.0315	0.093*
H7B	0.0171	0.0899	0.0765	0.093*
H7C	0.3703	0.2710	0.0599	0.093*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0898 (7)	0.0583 (7)	0.0610 (6)	0.0171 (5)	0.0109 (5)	−0.0070 (5)
O1	0.0875 (17)	0.0632 (18)	0.0575 (14)	−0.0044 (13)	0.0288 (13)	0.0043 (13)
O2	0.0669 (14)	0.0379 (14)	0.0472 (12)	0.0064 (11)	0.0127 (10)	−0.0011 (10)
N1	0.0611 (17)	0.0362 (17)	0.0564 (16)	0.0033 (13)	0.0081 (13)	0.0050 (14)
C1	0.0451 (18)	0.043 (2)	0.0472 (17)	0.0109 (16)	0.0029 (14)	0.0064 (16)
C2	0.0517 (19)	0.044 (2)	0.0505 (18)	0.0091 (16)	0.0165 (15)	0.0146 (16)
C3	0.0457 (17)	0.0346 (19)	0.0485 (17)	0.0021 (14)	0.0071 (14)	0.0060 (15)
C4	0.0394 (17)	0.042 (2)	0.0400 (16)	0.0105 (15)	0.0059 (13)	0.0138 (14)
C5	0.0509 (19)	0.042 (2)	0.0496 (17)	0.0048 (16)	0.0110 (14)	0.0112 (16)
C6	0.0450 (18)	0.046 (2)	0.0489 (18)	0.0112 (16)	0.0075 (15)	0.0093 (17)
C7	0.071 (2)	0.054 (2)	0.0551 (19)	0.0092 (18)	0.0116 (17)	−0.0019 (18)

Geometric parameters (Å, º) top

Cl1—C1	1.728 (3)	C3—H3	0.9300
O1—C6	1.198 (4)	C3—C4	1.382 (4)
O2—C6	1.333 (4)	C4—C5	1.376 (4)
O2—C7	1.444 (3)	C4—C6	1.482 (4)
N1—C1	1.322 (4)	C5—H5	0.9300
N1—C5	1.333 (3)	C7—H7A	0.9600
C1—C2	1.380 (4)	C7—H7B	0.9600
C2—H2	0.9300	C7—H7C	0.9600
C2—C3	1.367 (4)

C6—O2—C7	116.0 (2)	C5—C4—C6	118.1 (3)
C1—N1—C5	116.2 (3)	N1—C5—C4	124.2 (3)
N1—C1—Cl1	115.3 (2)	N1—C5—H5	117.9
N1—C1—C2	124.6 (3)	C4—C5—H5	117.9
C2—C1—Cl1	120.1 (2)	O1—C6—O2	123.3 (3)
C1—C2—H2	121.1	O1—C6—C4	124.1 (3)
C3—C2—C1	117.8 (3)	O2—C6—C4	112.6 (3)
C3—C2—H2	121.1	O2—C7—H7A	109.5
C2—C3—H3	120.2	O2—C7—H7B	109.5
C2—C3—C4	119.5 (3)	O2—C7—H7C	109.5
C4—C3—H3	120.2	H7A—C7—H7B	109.5
C3—C4—C6	124.3 (3)	H7A—C7—H7C	109.5
C5—C4—C3	117.7 (3)	H7B—C7—H7C	109.5

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C3—H3···N1ⁱ	0.93	2.59	3.440 (4)	151
C5—H5···O1	0.93	2.49	2.812 (3)	101

Symmetry code: (i) x−1, y−1, z.

Experimental details

Crystal data
Chemical formula	C₇H₆ClNO₂
M_r	171.58
Crystal system, space group	Triclinic, P1
Temperature (K)	293
a, b, c (Å)	3.8721 (4), 5.8068 (6), 17.3721 (18)
α, β, γ (°)	95.563 (9), 94.918 (8), 104.657 (9)
V (Å³)	373.64 (7)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.45
Crystal size (mm)	0.30 × 0.30 × 0.12

Data collection
Diffractometer	Oxford Diffraction Xcalibur E diffractometer
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2011)
T_min, T_max	0.037, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	3068, 1527, 855
R_int	0.029
(sin θ/λ)_max (Å⁻¹)	0.625

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.055, 0.119, 0.99
No. of reflections	1527
No. of parameters	101
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.23, −0.18

Computer programs: CrysAlis PRO (Agilent, 2011), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), OLEX2 (Dolomanov et al., 2009) and Mercury (Macrae et al., 2006), OLEX2 (Dolomanov et al., 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C3—H3···N1ⁱ	0.93	2.59	3.440 (4)	151

Symmetry code: (i) x−1, y−1, z.

Acknowledgements

We thank the Analytical and Testing Center of Sichuan University for the X-ray measurements.

References

Agilent (2011). CrysAlis PRO. Agilent Technologies, Yarnton, England. Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
González, M. A., Correa-Royero, J., Mesa, A. & Betancur-Galvis, L. (2009). Nat. Prod. Res. 23, 1485–1491. Web of Science PubMed Google Scholar
Ma, Y. & Liu, Y.-L. (2008). Acta Cryst. E64, o1072. Web of Science CSD CrossRef IUCr Journals Google Scholar
Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453–457. Web of Science CrossRef CAS IUCr Journals Google Scholar
Rekha, V. V., Ramani, M. V., Ratnamala, A., Rupakalpana, V., Subbaraju, G. V., Satyanarayana, C. & Rao, C. S. (2009). Org. Process Res. Dev. 13, 769–773. Web of Science CrossRef CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar