supplementary materials


gk2439 scheme

Acta Cryst. (2012). E68, o162    [ doi:10.1107/S1600536811053517 ]

Methyl 6-chloronicotinate

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

Abstract top

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 [pi]-[pi] stacking interactions between the aromatic rings in adjacent layers [centroid-centroid distance 3.8721 (4) Å]

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)
graphiteRint = 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 reflectionsθmax = 26.4°
Refinement top
R[F2 > 2σ(F2)] = 0.055H-atom parameters constrained
wR(F2) = 0.119Δρmax = 0.23 e Å3
S = 0.99Δρmin = 0.18 e Å3
1527 reflectionsAbsolute structure: ?
101 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
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, °) 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, °) 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 codes: (i) x−1, y−1, z.
Table 1
Hydrogen-bond geometry (Å, °)
top
D—H···AD—HH···AD···AD—H···A
C3—H3···N1i0.932.593.440 (4)151
Symmetry codes: (i) x−1, y−1, z.
Acknowledgements top

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

references
References top

Agilent (2011). CrysAlis PRO. Agilent Technologies, Yarnton, England.

Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341.

González, M. A., Correa-Royero, J., Mesa, A. & Betancur-Galvis, L. (2009). Nat. Prod. Res. 23, 1485–1491.

Ma, Y. & Liu, Y.-L. (2008). Acta Cryst. E64, o1072.

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.

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.

Sheldrick, G. M. (2008). Acta Cryst. A 64, 112-122.