Methyl 4,6-dichloro­pyridine-3-carboxyl­ate

Ma, Y.; Liu, J.

doi:10.1107/S1600536808011914

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 64| Part 6| June 2008| Page o995

doi:10.1107/S1600536808011914

Open

access

Methyl 4,6-dichloropyridine-3-carboxylate

Yi Ma ^a ^* and Jun Liu ^b

^aSchool of Chemical Engineering, Shandong Institute of Light Industry, Jinan 250353, People's Republic of China, and ^bJinan Sijian (Group) Co. Ltd, Jinan 250031, People's Republic of China
^*Correspondence e-mail: yima_2008@yahoo.cn

(Received 18 April 2008; accepted 24 April 2008; online 3 May 2008)

The title compound, C₇H₅Cl₂NO₂, crystallizes with two independent molecules in the asymmetric unit. The bond lengths and angles in both molecules are within normal ranges. In the crystal structure, weak intermolecular C—H⋯O hydrogen bonds link the molecules into layers parallel to the [010] plane.

Related literature

For details of the biological activity of the title compound, see: Wallace et al. (2006 ); Bondinell et al. (2002 ). For a related structure, see: McArdle et al. (1982 ).

Experimental

Crystal data

C₇H₅Cl₂NO₂
M_r = 206.02
Monoclinic, P 2₁ /c
a = 8.033 (4) Å
b = 18.974 (9) Å
c = 11.240 (6) Å
β = 95.224 (8)°
V = 1705.9 (15) Å³
Z = 8
Mo Kα radiation
μ = 0.71 mm⁻¹
T = 298 (2) K
0.45 × 0.19 × 0.06 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2004 ) T_min = 0.739, T_max = 0.958
8532 measured reflections
3012 independent reflections
2289 reflections with I > 2σ(I)
R_int = 0.035

Refinement

R[F² > 2σ(F²)] = 0.052
wR(F²) = 0.135
S = 1.08
3012 reflections
217 parameters
H-atom parameters constrained
Δρ_max = 0.25 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
C6—H6A⋯O3ⁱ	0.93	2.41	3.309 (4)	162
C11—H11A⋯O2ⁱⁱ	0.93	2.60	3.513 (4)	168
Symmetry codes: (i) $[-x+1, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ ; (ii) x-1, y, z-1.

Data collection: SMART (Bruker, 2001 ); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and local programs.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808011914/hg2396sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808011914/hg2396Isup2.hkl

checkCIF report

Comment top

Methyl 4,6-dichloropyridine-3-carboxylate is a useful intermediate for the synthesis of different kinase inhibitors (Wallace et al., 2006; Bondinell et al., 2002). In this paper, we report the crystal structure of the title compound (I).

Compound (I) crystallizes with two independent molecules in the asymmetric unit (Fig. 1), all bond lengths and angles are normal and in a good agreement with those reported previously (McArdle et al., 1982). The dihedral angles between the planes of the methoxycarbonyl group (C1/C2/O1/O2; C8/C9/O3/O4) and pyridine rings in the two independent molecules are 10.9 (2) and 8.1 (4)°. In the crystal structure, weak intermolecular C—H···O hydrogen bonds link the molecules into layers parallel to the b axis.

Related literature top

For the biological activity of the title compound, see: Wallace et al. (2006); Bondinell et al. (2002). For a related structure, see: McArdle et al. (1982).

Experimental top

Methyl 4, 6-dichloropyridine-3-carboxylate was synthesized from Methyl 4, 6-dihydroxypyridine-3-carboxylate via chlorination with POCl₃. The desired compound was obtained as a low melting yellow solid in 89% yield. Crystals suitable for X-ray diffraction analysis were obtained by slow evaporation of a solution in a hexane/dichloromethane mixture (1: 4 v/v) at room temperature over a period of one week.

Computing details top

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and local programs.

Figures top

Fig. 1. View of the title compound (I), with displacement ellipsoids drawn at the 40% probability level.

Methyl 4,6-dichloropyridine-3-carboxylate top

Crystal data top

C₇H₅Cl₂NO₂	F(000) = 832
M_r = 206.02	D_x = 1.604 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 1274 reflections
a = 8.033 (4) Å	θ = 2.8–27.9°
b = 18.974 (9) Å	µ = 0.72 mm⁻¹
c = 11.240 (6) Å	T = 298 K
β = 95.224 (8)°	Block, colorless
V = 1705.9 (15) Å³	0.45 × 0.19 × 0.06 mm
Z = 8

Data collection top

Bruker SMART CCD area-detector diffractometer	3012 independent reflections
Radiation source: fine-focus sealed tube	2289 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.035
ϕ and ω scans	θ_max = 25.0°, θ_min = 2.1°
Absorption correction: multi-scan (SADABS; Sheldrick, 2004)	h = −9→9
T_min = 0.739, T_max = 0.958	k = −16→22
8532 measured reflections	l = −12→13

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)] = 0.052	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.135	H-atom parameters constrained
S = 1.08	w = 1/[σ²(F_o²) + (0.0645P)² + 0.3441P] where P = (F_o² + 2F_c²)/3
3012 reflections	(Δ/σ)_max = 0.001
217 parameters	Δρ_max = 0.25 e Å⁻³
0 restraints	Δρ_min = −0.18 e Å⁻³

Crystal data top

C₇H₅Cl₂NO₂	V = 1705.9 (15) Å³
M_r = 206.02	Z = 8
Monoclinic, P2₁/c	Mo Kα radiation
a = 8.033 (4) Å	µ = 0.72 mm⁻¹
b = 18.974 (9) Å	T = 298 K
c = 11.240 (6) Å	0.45 × 0.19 × 0.06 mm
β = 95.224 (8)°

Data collection top

Bruker SMART CCD area-detector diffractometer	3012 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 2004)	2289 reflections with I > 2σ(I)
T_min = 0.739, T_max = 0.958	R_int = 0.035
8532 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.052	0 restraints
wR(F²) = 0.135	H-atom parameters constrained
S = 1.08	Δρ_max = 0.25 e Å⁻³
3012 reflections	Δρ_min = −0.18 e Å⁻³
217 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	0.31475 (11)	0.33695 (5)	0.64891 (7)	0.0715 (3)
Cl4	0.81189 (12)	0.14450 (4)	1.15267 (7)	0.0730 (3)
Cl3	0.49419 (14)	0.01243 (5)	0.78099 (8)	0.0883 (4)
Cl2	0.16454 (16)	0.07877 (5)	0.49234 (11)	0.1033 (4)
O4	0.0012 (3)	0.39718 (12)	0.3185 (2)	0.0810 (7)
O1	0.6147 (3)	0.33347 (11)	0.9518 (2)	0.0761 (7)
C3	0.6515 (3)	0.21244 (15)	0.9614 (2)	0.0494 (7)
C4	0.5571 (4)	0.20765 (17)	0.8514 (3)	0.0629 (8)
H4A	0.5253	0.2497	0.8133	0.075*
O2	0.7987 (3)	0.29383 (12)	1.0946 (2)	0.0859 (8)
C6	0.6496 (4)	0.08658 (16)	0.9608 (3)	0.0586 (8)
H6A	0.6799	0.0434	0.9955	0.070*
N1	0.5088 (4)	0.14837 (15)	0.7965 (2)	0.0676 (7)
C10	0.1250 (3)	0.30967 (15)	0.4395 (2)	0.0496 (7)
C11	0.0479 (4)	0.25996 (16)	0.3617 (3)	0.0570 (8)
H11A	−0.0152	0.2765	0.2940	0.068*
C13	0.2303 (4)	0.21170 (16)	0.5586 (3)	0.0585 (8)
H13A	0.2924	0.1930	0.6251	0.070*
O3	0.1841 (4)	0.43167 (13)	0.4631 (2)	0.1010 (10)
C5	0.5558 (4)	0.09031 (17)	0.8522 (3)	0.0603 (8)
C7	0.6965 (4)	0.14869 (15)	1.0159 (2)	0.0504 (7)
C9	0.1096 (4)	0.38562 (17)	0.4109 (3)	0.0574 (8)
C1	0.6574 (6)	0.40446 (18)	0.9884 (4)	0.0940 (13)
H1B	0.5889	0.4371	0.9405	0.141*
H1C	0.7730	0.4131	0.9781	0.141*
H1D	0.6388	0.4105	1.0710	0.141*
N2	0.0578 (3)	0.19055 (14)	0.3773 (2)	0.0640 (7)
C14	0.2165 (4)	0.28322 (15)	0.5410 (2)	0.0505 (7)
C2	0.6989 (4)	0.28237 (16)	1.0116 (3)	0.0552 (7)
C8	−0.0218 (5)	0.46966 (19)	0.2809 (3)	0.0893 (12)
H8A	−0.1038	0.4719	0.2133	0.134*
H8B	0.0823	0.4883	0.2591	0.134*
H8C	−0.0592	0.4969	0.3453	0.134*
C12	0.1485 (4)	0.16916 (16)	0.4737 (3)	0.0612 (8)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0777 (6)	0.0746 (6)	0.0578 (5)	−0.0105 (4)	−0.0170 (4)	−0.0072 (4)
Cl4	0.0903 (7)	0.0682 (5)	0.0546 (5)	0.0025 (4)	−0.0261 (4)	0.0098 (4)
Cl3	0.1127 (9)	0.0703 (6)	0.0774 (6)	−0.0146 (5)	−0.0161 (5)	−0.0120 (4)
Cl2	0.1327 (10)	0.0557 (5)	0.1145 (8)	0.0077 (6)	−0.0265 (7)	−0.0019 (5)
O4	0.0964 (19)	0.0624 (14)	0.0776 (15)	−0.0033 (13)	−0.0278 (14)	0.0115 (12)
O1	0.0920 (18)	0.0560 (13)	0.0748 (15)	0.0027 (12)	−0.0222 (12)	0.0056 (11)
C3	0.0457 (17)	0.0590 (18)	0.0425 (15)	0.0017 (13)	−0.0020 (12)	0.0062 (13)
C4	0.072 (2)	0.0584 (19)	0.0548 (18)	−0.0003 (16)	−0.0144 (15)	0.0074 (15)
O2	0.107 (2)	0.0698 (16)	0.0729 (15)	−0.0033 (14)	−0.0369 (14)	−0.0034 (12)
C6	0.064 (2)	0.0565 (18)	0.0530 (18)	0.0022 (15)	−0.0044 (15)	0.0079 (14)
N1	0.076 (2)	0.0683 (18)	0.0538 (15)	−0.0015 (14)	−0.0175 (13)	0.0034 (13)
C10	0.0448 (17)	0.0594 (18)	0.0444 (15)	−0.0022 (14)	0.0035 (12)	−0.0019 (13)
C11	0.059 (2)	0.064 (2)	0.0466 (16)	−0.0005 (15)	−0.0042 (14)	−0.0028 (14)
C13	0.0565 (19)	0.066 (2)	0.0509 (17)	0.0018 (15)	−0.0056 (14)	0.0038 (14)
O3	0.136 (3)	0.0614 (16)	0.0958 (19)	−0.0204 (15)	−0.0430 (18)	0.0030 (13)
C5	0.064 (2)	0.063 (2)	0.0528 (17)	−0.0050 (16)	−0.0029 (15)	−0.0045 (15)
C7	0.0465 (17)	0.0616 (18)	0.0418 (15)	0.0028 (14)	−0.0031 (12)	0.0062 (13)
C9	0.058 (2)	0.064 (2)	0.0501 (17)	−0.0045 (16)	−0.0014 (15)	0.0015 (15)
C1	0.133 (4)	0.053 (2)	0.090 (3)	0.003 (2)	−0.020 (2)	−0.0003 (18)
N2	0.0729 (19)	0.0568 (16)	0.0602 (16)	−0.0026 (13)	−0.0062 (13)	−0.0087 (13)
C14	0.0462 (17)	0.0586 (18)	0.0464 (16)	−0.0040 (13)	0.0034 (13)	−0.0036 (13)
C2	0.061 (2)	0.0597 (18)	0.0445 (16)	0.0022 (15)	0.0002 (14)	0.0054 (14)
C8	0.105 (3)	0.068 (2)	0.090 (3)	0.002 (2)	−0.016 (2)	0.0210 (19)
C12	0.064 (2)	0.0546 (18)	0.064 (2)	0.0040 (15)	−0.0002 (16)	−0.0012 (15)

Geometric parameters (Å, º) top

Cl1—C14	1.720 (3)	N1—C5	1.306 (4)
Cl4—C7	1.723 (3)	C10—C11	1.392 (4)
Cl3—C5	1.731 (3)	C10—C14	1.393 (4)
Cl2—C12	1.731 (3)	C10—C9	1.479 (4)
O4—C9	1.313 (4)	C11—N2	1.330 (4)
O4—C8	1.446 (4)	C11—H11A	0.9300
O1—C2	1.329 (4)	C13—C12	1.371 (4)
O1—C1	1.441 (4)	C13—C14	1.374 (4)
C3—C7	1.389 (4)	C13—H13A	0.9300
C3—C4	1.393 (4)	O3—C9	1.184 (4)
C3—C2	1.478 (4)	C1—H1B	0.9600
C4—N1	1.324 (4)	C1—H1C	0.9600
C4—H4A	0.9300	C1—H1D	0.9600
O2—C2	1.194 (4)	N2—C12	1.314 (4)
C6—C7	1.368 (4)	C8—H8A	0.9600
C6—C5	1.376 (4)	C8—H8B	0.9600
C6—H6A	0.9300	C8—H8C	0.9600

C9—O4—C8	116.6 (3)	C3—C7—Cl4	122.1 (2)
C2—O1—C1	116.2 (3)	O3—C9—O4	122.6 (3)
C7—C3—C4	115.7 (3)	O3—C9—C10	125.7 (3)
C7—C3—C2	124.4 (2)	O4—C9—C10	111.8 (3)
C4—C3—C2	119.8 (3)	O1—C1—H1B	109.5
N1—C4—C3	125.6 (3)	O1—C1—H1C	109.5
N1—C4—H4A	117.2	H1B—C1—H1C	109.5
C3—C4—H4A	117.2	O1—C1—H1D	109.5
C7—C6—C5	117.6 (3)	H1B—C1—H1D	109.5
C7—C6—H6A	121.2	H1C—C1—H1D	109.5
C5—C6—H6A	121.2	C12—N2—C11	115.9 (3)
C5—N1—C4	115.7 (3)	C13—C14—C10	120.2 (3)
C11—C10—C14	116.2 (3)	C13—C14—Cl1	117.2 (2)
C11—C10—C9	120.0 (3)	C10—C14—Cl1	122.5 (2)
C14—C10—C9	123.8 (3)	O2—C2—O1	122.5 (3)
N2—C11—C10	124.8 (3)	O2—C2—C3	126.4 (3)
N2—C11—H11A	117.6	O1—C2—C3	111.2 (3)
C10—C11—H11A	117.6	O4—C8—H8A	109.5
C12—C13—C14	117.0 (3)	O4—C8—H8B	109.5
C12—C13—H13A	121.5	H8A—C8—H8B	109.5
C14—C13—H13A	121.5	O4—C8—H8C	109.5
N1—C5—C6	125.4 (3)	H8A—C8—H8C	109.5
N1—C5—Cl3	116.1 (2)	H8B—C8—H8C	109.5
C6—C5—Cl3	118.5 (2)	N2—C12—C13	125.9 (3)
C6—C7—C3	120.0 (3)	N2—C12—Cl2	115.8 (2)
C6—C7—Cl4	117.9 (2)	C13—C12—Cl2	118.2 (2)

C7—C3—C4—N1	−0.2 (5)	C11—C10—C9—O4	8.7 (4)
C2—C3—C4—N1	179.1 (3)	C14—C10—C9—O4	−172.4 (3)
C3—C4—N1—C5	−0.1 (5)	C10—C11—N2—C12	−0.3 (5)
C14—C10—C11—N2	−0.9 (4)	C12—C13—C14—C10	−1.1 (4)
C9—C10—C11—N2	178.0 (3)	C12—C13—C14—Cl1	178.5 (2)
C4—N1—C5—C6	−0.1 (5)	C11—C10—C14—C13	1.6 (4)
C4—N1—C5—Cl3	−179.7 (2)	C9—C10—C14—C13	−177.3 (3)
C7—C6—C5—N1	0.6 (5)	C11—C10—C14—Cl1	−178.0 (2)
C7—C6—C5—Cl3	−179.8 (2)	C9—C10—C14—Cl1	3.1 (4)
C5—C6—C7—C3	−0.9 (5)	C1—O1—C2—O2	3.5 (5)
C5—C6—C7—Cl4	179.3 (2)	C1—O1—C2—C3	−176.6 (3)
C4—C3—C7—C6	0.7 (4)	C7—C3—C2—O2	11.1 (5)
C2—C3—C7—C6	−178.5 (3)	C4—C3—C2—O2	−168.0 (3)
C4—C3—C7—Cl4	−179.5 (2)	C7—C3—C2—O1	−168.8 (3)
C2—C3—C7—Cl4	1.3 (4)	C4—C3—C2—O1	12.0 (4)
C8—O4—C9—O3	1.1 (5)	C11—N2—C12—C13	0.9 (5)
C8—O4—C9—C10	−178.8 (3)	C11—N2—C12—Cl2	−178.8 (2)
C11—C10—C9—O3	−171.2 (3)	C14—C13—C12—N2	−0.2 (5)
C14—C10—C9—O3	7.7 (5)	C14—C13—C12—Cl2	179.5 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C6—H6A···O3ⁱ	0.93	2.41	3.309 (4)	162
C11—H11A···O2ⁱⁱ	0.93	2.60	3.513 (4)	168

Symmetry codes: (i) −x+1, y−1/2, −z+3/2; (ii) x−1, y, z−1.

Experimental details

Crystal data
Chemical formula	C₇H₅Cl₂NO₂
M_r	206.02
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	298
a, b, c (Å)	8.033 (4), 18.974 (9), 11.240 (6)
β (°)	95.224 (8)
V (Å³)	1705.9 (15)
Z	8
Radiation type	Mo Kα
µ (mm⁻¹)	0.72
Crystal size (mm)	0.45 × 0.19 × 0.06

Data collection
Diffractometer	Bruker SMART CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Sheldrick, 2004)
T_min, T_max	0.739, 0.958
No. of measured, independent and observed [I > 2σ(I)] reflections	8532, 3012, 2289
R_int	0.035
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.052, 0.135, 1.08
No. of reflections	3012
No. of parameters	217
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.25, −0.18

Computer programs: SMART (Bruker, 2001), SAINT (Bruker, 2001), SHELXTL (Sheldrick, 2008) and local programs.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C6—H6A···O3ⁱ	0.93	2.41	3.309 (4)	162.2
C11—H11A···O2ⁱⁱ	0.93	2.60	3.513 (4)	167.5

Symmetry codes: (i) −x+1, y−1/2, −z+3/2; (ii) x−1, y, z−1.

References

Bondinell, W. E., Holt, D. A., Lago, M. A., Neeb, M. J. & Semones, M. A. (2002). World Wide Patent. WO 02 076 463. Google Scholar
Bruker (2001). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
McArdle, J. V., de Laubenfels, E., Shorter, A. L. & Ammon, H. L. (1982). Polyhedron, 1, 471–474. CSD CrossRef CAS Web of Science Google Scholar
Sheldrick, G. M. (2004). SADABS. University of Göttingen, Germany. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Wallace, E., Hurley, B., Yang, H. W., Lyssikatos, J. & Blake, J. (2006). United States Patent US 7 144 907. Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 64| Part 6| June 2008| Page o995

doi:10.1107/S1600536808011914

Open

access