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ISSN: 2056-9890

Methyl 6-chloro­nicotinate

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 ππ 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[González, M. A., Correa-Royero, J., Mesa, A. & Betancur-Galvis, L. (2009). Nat. Prod. Res. 23, 1485-1491.]); Rekha et al. (2009[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.]). For a related structure, see: Ma & Liu (2008[Ma, Y. & Liu, Y.-L. (2008). Acta Cryst. E64, o1072.]).

[Scheme 1]

Experimental

Crystal data
  • C7H6ClNO2

  • Mr = 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[Agilent (2011). CrysAlis PRO. Agilent Technologies, Yarnton, England.]) Tmin = 0.037, Tmax = 1.000

  • 3068 measured reflections

  • 1527 independent reflections

  • 855 reflections with I > 2σ(I)

  • Rint = 0.029

Refinement
  • R[F2 > 2σ(F2)] = 0.055

  • wR(F2) = 0.119

  • S = 0.99

  • 1527 reflections

  • 101 parameters

  • H-atom parameters constrained

  • Δρmax = 0.23 e Å−3

  • Δρmin = −0.18 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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[Agilent (2011). CrysAlis PRO. Agilent Technologies, Yarnton, England.]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]) and Mercury (Macrae et al., 2006[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.]); software used to prepare material for publication: OLEX2.

Supporting information


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.

Refinement top

H atoms were positioned geometrically and refined using a riding model approximation, with d(C—H) = 0.93 - 0.96 Å, and Uiso(H) =1.2Ueq(C) or 1.5Ueq(methyl C).

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
[Figure 1] Fig. 1. The molecular structure of the title compound with displacement ellipsoids drawn at the 30% probability level.
[Figure 2] 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
C7H6ClNO2Z = 2
Mr = 171.58F(000) = 176
Triclinic, P1Dx = 1.525 Mg m3
a = 3.8721 (4) ÅMo Kα radiation, λ = 0.7107 Å
b = 5.8068 (6) ÅCell parameters from 741 reflections
c = 17.3721 (18) Åθ = 3.6–26.3°
α = 95.563 (9)°µ = 0.45 mm1
β = 94.918 (8)°T = 293 K
γ = 104.657 (9)°Block, colourless
V = 373.64 (7) Å30.30 × 0.30 × 0.12 mm
Data collection top
Oxford Diffraction Xcalibur E
diffractometer
1527 independent reflections
Radiation source: Enhance (Mo) X-ray Source855 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.029
Detector resolution: 16.0874 pixels mm-1θmax = 26.4°, θmin = 3.6°
ω scansh = 44
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2011)
k = 77
Tmin = 0.037, Tmax = 1.000l = 2121
3068 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.055Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.119H-atom parameters constrained
S = 0.99 w = 1/[σ2(Fo2) + (0.041P)2]
where P = (Fo2 + 2Fc2)/3
1527 reflections(Δ/σ)max < 0.001
101 parametersΔρmax = 0.23 e Å3
0 restraintsΔρmin = 0.18 e Å3
Crystal data top
C7H6ClNO2γ = 104.657 (9)°
Mr = 171.58V = 373.64 (7) Å3
Triclinic, P1Z = 2
a = 3.8721 (4) ÅMo Kα radiation
b = 5.8068 (6) ŵ = 0.45 mm1
c = 17.3721 (18) ÅT = 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)
Tmin = 0.037, Tmax = 1.000Rint = 0.029
3068 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0550 restraints
wR(F2) = 0.119H-atom parameters constrained
S = 0.99Δρmax = 0.23 e Å3
1527 reflectionsΔρmin = 0.18 e Å3
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
xyzUiso*/Ueq
Cl10.3480 (2)1.23478 (16)0.44450 (4)0.0710 (4)
O10.4875 (6)0.7116 (4)0.10003 (12)0.0728 (8)
O20.1351 (5)0.3994 (4)0.14496 (10)0.0521 (6)
N10.5039 (6)1.1467 (5)0.30475 (15)0.0529 (7)
C10.3350 (8)1.0448 (6)0.36075 (16)0.0452 (8)
C20.1561 (7)0.8050 (6)0.35567 (17)0.0480 (8)
H20.04350.74210.39710.058*
C30.1498 (7)0.6630 (6)0.28773 (15)0.0443 (8)
H30.03310.50030.28230.053*
C40.3182 (7)0.7630 (5)0.22726 (15)0.0399 (7)
C50.4935 (7)1.0035 (5)0.23934 (17)0.0484 (8)
H50.61251.07040.19930.058*
C60.3266 (8)0.6273 (6)0.15097 (18)0.0464 (8)
C70.1289 (8)0.2550 (6)0.07211 (16)0.0618 (10)
H7A0.00500.30800.03150.093*
H7B0.01710.08990.07650.093*
H7C0.37030.27100.05990.093*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0898 (7)0.0583 (7)0.0610 (6)0.0171 (5)0.0109 (5)0.0070 (5)
O10.0875 (17)0.0632 (18)0.0575 (14)0.0044 (13)0.0288 (13)0.0043 (13)
O20.0669 (14)0.0379 (14)0.0472 (12)0.0064 (11)0.0127 (10)0.0011 (10)
N10.0611 (17)0.0362 (17)0.0564 (16)0.0033 (13)0.0081 (13)0.0050 (14)
C10.0451 (18)0.043 (2)0.0472 (17)0.0109 (16)0.0029 (14)0.0064 (16)
C20.0517 (19)0.044 (2)0.0505 (18)0.0091 (16)0.0165 (15)0.0146 (16)
C30.0457 (17)0.0346 (19)0.0485 (17)0.0021 (14)0.0071 (14)0.0060 (15)
C40.0394 (17)0.042 (2)0.0400 (16)0.0105 (15)0.0059 (13)0.0138 (14)
C50.0509 (19)0.042 (2)0.0496 (17)0.0048 (16)0.0110 (14)0.0112 (16)
C60.0450 (18)0.046 (2)0.0489 (18)0.0112 (16)0.0075 (15)0.0093 (17)
C70.071 (2)0.054 (2)0.0551 (19)0.0092 (18)0.0116 (17)0.0019 (18)
Geometric parameters (Å, º) top
Cl1—C11.728 (3)C3—H30.9300
O1—C61.198 (4)C3—C41.382 (4)
O2—C61.333 (4)C4—C51.376 (4)
O2—C71.444 (3)C4—C61.482 (4)
N1—C11.322 (4)C5—H50.9300
N1—C51.333 (3)C7—H7A0.9600
C1—C21.380 (4)C7—H7B0.9600
C2—H20.9300C7—H7C0.9600
C2—C31.367 (4)
C6—O2—C7116.0 (2)C5—C4—C6118.1 (3)
C1—N1—C5116.2 (3)N1—C5—C4124.2 (3)
N1—C1—Cl1115.3 (2)N1—C5—H5117.9
N1—C1—C2124.6 (3)C4—C5—H5117.9
C2—C1—Cl1120.1 (2)O1—C6—O2123.3 (3)
C1—C2—H2121.1O1—C6—C4124.1 (3)
C3—C2—C1117.8 (3)O2—C6—C4112.6 (3)
C3—C2—H2121.1O2—C7—H7A109.5
C2—C3—H3120.2O2—C7—H7B109.5
C2—C3—C4119.5 (3)O2—C7—H7C109.5
C4—C3—H3120.2H7A—C7—H7B109.5
C3—C4—C6124.3 (3)H7A—C7—H7C109.5
C5—C4—C3117.7 (3)H7B—C7—H7C109.5
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C3—H3···N1i0.932.593.440 (4)151
C5—H5···O10.932.492.812 (3)101
Symmetry code: (i) x1, y1, z.

Experimental details

Crystal data
Chemical formulaC7H6ClNO2
Mr171.58
Crystal system, space groupTriclinic, 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)
V3)373.64 (7)
Z2
Radiation typeMo Kα
µ (mm1)0.45
Crystal size (mm)0.30 × 0.30 × 0.12
Data collection
DiffractometerOxford Diffraction Xcalibur E
diffractometer
Absorption correctionMulti-scan
(CrysAlis PRO; Agilent, 2011)
Tmin, Tmax0.037, 1.000
No. of measured, independent and
observed [I > 2σ(I)] reflections
3068, 1527, 855
Rint0.029
(sin θ/λ)max1)0.625
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.055, 0.119, 0.99
No. of reflections1527
No. of parameters101
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)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···AD—HH···AD···AD—H···A
C3—H3···N1i0.932.593.440 (4)151
Symmetry code: (i) x1, y1, z.
 

Acknowledgements

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

References

First citationAgilent (2011). CrysAlis PRO. Agilent Technologies, Yarnton, England.
First citationDolomanov, 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
First citationGonzález, M. A., Correa-Royero, J., Mesa, A. & Betancur-Galvis, L. (2009). Nat. Prod. Res. 23, 1485–1491.  Web of Science PubMed
First citationMa, Y. & Liu, Y.-L. (2008). Acta Cryst. E64, o1072.  Web of Science CSD CrossRef IUCr Journals
First citationMacrae, 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
First citationRekha, 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
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals

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COMMUNICATIONS
ISSN: 2056-9890
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