Di­ethyl 2,6 di­methyl­pyridine 3,5 di­carboxyl­ate

organic papers

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13H17NO4 doi:10.1107/S1600536805039590 Acta Cryst.(2006). E62, o24–o25 Acta Crystallographica Section E

Structure Reports

Online

ISSN 1600-5368

Diethyl 2,6-dimethylpyridine-3,5-dicarboxylate

Jian-Zhong Cui,* Hong Zhang, Dan Zhang, Hai-Tao Wang and Hong-Ling Gao

Department of Chemistry, Tianjin University, Tianjin 300072, People’s Republic of China

Correspondence e-mail: cuijianzhong@tju.edu.cn

Key indicators

Single-crystal X-ray study

T= 294 K

Mean(C–C) = 0.004 A˚ Disorder in main residue

Rfactor = 0.049

wRfactor = 0.155

Data-to-parameter ratio = 13.0

For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.

#2006 International Union of Crystallography Printed in Great Britain – all rights reserved

The molecular structure of the title compound, C13H17NO4, has no symmetry plane because one C atom of the ethyl group lies out of the plane defined by the other non-H atoms. In the crystal structure, the molecules stack along the a axis. Symmetry-related molecules are linked by a C—H O hydrogen bond, forming zigzag chains extending in theb-axis direction.

Comment

Dihydropyridine compounds are calcium ion channel blockers and the use of these compounds is generally beneficial (Bo¨cker et al., 1986). Aromatization of Hantzsch 1,4-dihydropyridines (1,4-DHP) has attracted considerable attention in recent years, essentially since the discovery that the metabolism of these drugs involves an oxidation step (Eyndeet al.,1995). Here we describe the synthesis (Luet al., 2001) and crystal structure of the title compound, (I).

The molecular structure of the compound (I) is shown in Fig. 1 and selected geometric parameters are given in Table 1. All of the non-H atoms in (I) lie almost in the same plane, except atom C10 which is out of the plane with a C8—O2— C9—C10 torsion angle of 123.2 (17)_{. This is probably because}

of the disorder of the ethyl group, and for this reason the molecule has no symmetry plane.

In the crystal structure of (I), the molecules stack along the

aaxis and are linked by C—H O hydrogen bonds, forming polymer chains extending in the b-axis direction (Table 2, Fig. 2).

Experimental

The title compound, (I) was prepared according to the literature procedure of Luet al.(2001). A mixture of diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, ferric chloride hexahydrate, acetic acid and water was heated at reflux for 1 h. After neutralization with an aqueous solution of sodium bicarbornate and extraction with chloroform, the title compound was obtained (yield 52%; m.p. 343–

obtained by slow evaporation of an ethanol solution. IR (KBr, cm1): 2979, 2932, 1721, 1591, 1442, 1367, 1296, 1223, 1120, 1043, 771, 698.

Crystal data

C13H17NO4

Mr= 251.28

Monoclinic,P2₁=c a= 4.593 (2) A˚

b= 15.950 (9) A˚

c= 18.795 (10) A˚

= 90.656 (9)

V= 1376.9 (13) A˚3

Z= 4

Dx= 1.212 Mg m

3 MoKradiation Cell parameters from 1328

reflections

= 2.5–23.6

= 0.09 mm1

T= 294 (2) K Block, colorless 0.240.200.16 mm

Data collection

Bruker SMART CCD area-detector diffractometer

’and!scans

Absorption correction: multi-scan (SADABS; Sheldrick, 1996)

Tmin= 0.960,Tmax= 0.986 6854 measured reflections

2427 independent reflections 1158 reflections withI> 2(I)

Rint= 0.046

max= 25.0

h=4!5

k=18!12

l=22!22

Refinement

Refinement onF2

R[F2_{> 2(F}2_{)] = 0.049}

wR(F2_{) = 0.155}

S= 1.00 2427 reflections 187 parameters

H-atom parameters constrained

w= 1/[2_(F

o2) + (0.0658P)2 + 0.2484P]

whereP= (Fo2+ 2Fc2)/3 (/)max= 0.002

max= 0.20 e A˚ 3

min=0.14 e A˚ 3

Table 1

Selected torsion angles (_).

C8—O2—C9—C10 123.2 (17) C11—O4—C12—C13 178.7 (3)

Table 2

Hydrogen-bond geometry (A˚ ,_).

D—H A D—H H A D A D—H A

C12—H12B O1i

0.97 2.52 3.346 (4) 143

Symmetry code: (i)xþ2;y1 2;zþ

1 2.

All H atoms were positioned geometrically and refined as riding atoms with C—H distances = 0.93–0.97 A˚ . For the aromatic and CH2

H atoms Uiso(H) = 1.2Ue(C), and for the CH3H atoms Uiso(H) =

1.5Ueq(C). The ethyl group was found to be disordered over two

orientations, with occupancies of 0.39 (2) and 0.61 (2).

Data collection:SMART(Bruker, 1997); cell refinement:SAINT

(Bruker, 1997); data reduction: SAINT; program(s) used to solve structure: SHELXS97(Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics:

SHELXTL (Bruker, 1997); software used to prepare material for publication:SHELXTL.

References

Bo¨cker, R. H., Guengerich, F. P. (1986).J. Med. Chem.29, 1596–1603. Bruker (1997).SMART(Version 5.1),SAINT(Version 5.1) andSHELXTL

(Version 5.10). Bruker AXS Inc., Madison, Wiscosin, USA.

Eynde, J. J. V., Delfosse, F., Mayence, A. & Haverbeke, Y. V. (1995).

Tetrohedron.51, 6511–6516.

Lu, J., Bai, Y. J. Wang, Z. J., Yang, B. Q. & Li, W. H. (2001).Synth. Comm.31, Figure 1

The molecular structure of compound (I), showing the atom-labeling scheme, with displacement ellipsoids drawn at the 35% probability level. Only the major component of the disordered ethyl group is shown.

Figure 2

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Acta Cryst. (2006). E62, o24–o25 [doi:10.1107/S1600536805039590]

Diethyl 2,6-dimethylpyridine-3,5-dicarboxylate

Jian-Zhong Cui, Hong Zhang, Dan Zhang, Hai-Tao Wang and Hong-Ling Gao

S1. Comment

Dihydropyridine compounds are calcium ion channel blockers and the use of these compounds is generally beneficial

(Böcker et al., 1986). Aromatization of Hantzsch 1,4-dihydropyridines (1,4-DHP) has attracted considerable attention in

recent years, essentially since the discovery that the metabolism of these drugs involves an oxidation step (Eynde et

al.,1995). Here we describe the synthesis (Lu et al., 2001) and crystal structure of the title compound, (I).

The molecular structure of the compound (I) is shown in Fig. 1 and selected geometric parameters are given in Table 1.

A l l of the non-H atoms in (I) lie almost in the same plane, except atom C10 which is out of the plane with a C8—O2—

C9—C10 torsion angle of 123.2 (17)°. This is probably because of the disorder of the ethyl group, and for this reason the

molecule has no symmetry plane.

In the crystal structure of (I), the molecules stack along the a axis and are linked by C—H···O hydrogen bonds, forming

polymer chains extending in the b-axis direction (see Table 2 and Fig. 2 for details).

S2. Experimental

The title compound, (I) was prepared according to the literature procedure of Lu et al. (2001). A mixture of diethyl

2,6-dimethyl-1,4- dihydropyridine-3,5-dicarboxylate, ferric chloride hexahydrate, acetic acid and water was heated at reflux

for 1 h. After neutralization with an aqueous solution of sodium bicarbornate and extraction with chloroform, the title

compound was obtained (yield 52%; m.p. 343–344 K). Single crystals, suitable for X-ray diffraction analysis, were

obtained by slow evaporation of an ethanol solution. IR (KBr, ν cm−1_{): 2979, 2932, 1721, 1591, 1442, 1367, 1296, 1223,}

1120, 1043, 771, 698.

S3. Refinement

All the H atoms were positioned geometrically and refined as riding atoms with C—H distances = 0.93–0.97 Å. For the

aromatic and CH2 H atoms Uiso(H) = 1.2Ue(C), and for the CH3 Hatoms Uiso(H) = 1.5Ueq(C). The ethyl group was found to

Figure 1

The molecular structure of compound (I), showing the atom-labelling scheme, with displacement ellipsolids drawn at the

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Figure 2

The crystal packing of compound (I), viewed along the a axis. Only the major component of the disordered ethyl group is

shown. The C—H···O hydrogen bonds are shown as dashed lines.

Diethyl 2,6-dimethylpyridine-3,5-dicarboxylate

Crystal data

C13H17NO4 Mr = 251.28 Monoclinic, P21/c

Hall symbol: -P 2ybc

a = 4.593 (2) Å

b = 15.950 (9) Å

c = 18.795 (10) Å

β = 90.656 (9)°

V = 1376.9 (13) Å3 Z = 4

F(000) = 536

Dx = 1.212 Mg m−3

Melting point: 343 K

Mo Kα radiation, λ = 0.71073 Å Cell parameters from 1328 reflections

θ = 2.5–23.6°

µ = 0.09 mm−1 T = 294 K Block, colorless 0.24 × 0.20 × 0.16 mm

Data collection

Bruker SMART CCD area-detector diffractometer

Radiation source: fine-focus sealed tube Graphite monochromator

φ and ω scans

Absorption correction: multi-scan

(SADABS; Sheldrick, 1996)

Tmin = 0.960, Tmax = 0.986

6854 measured reflections 2427 independent reflections 1158 reflections with I > 2σ(I)

Rint = 0.046

θmax = 25.0°, θmin = 1.7°

h = −4→5

k = −18→12

Refinement on F2

Least-squares matrix: full

R[F2 _{> 2σ(F}2_{)] = 0.049} wR(F2_{) = 0.155} S = 1.00 2427 reflections 187 parameters 29 restraints

Primary atom site location: structure-invariant direct methods

Secondary atom site location: difference Fourier map

Hydrogen site location: inferred from neighbouring sites

H-atom parameters constrained

w = 1/[σ2_(Fo2_{) + (0.0658P)}2 _{+ 0.2484P]}

where P = (Fo2 _{+ 2Fc}2_)/3

(Δ/σ)max = 0.002

Δρmax = 0.20 e Å−3

Δρmin = −0.14 e Å−3

Special details

Refinement. Refinement of F2 _{against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F}2_,

conventional R-factors R are based on F, with F set to zero for negative F2_{. The threshold expression of F}2 _{> σ(F}2_{) 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₎

x y z Uiso*/Ueq Occ. (<1)

O1 1.2765 (6) 1.00909 (17) 0.29361 (13) 0.1091 (9) O2 1.0690 (5) 0.93288 (15) 0.20975 (12) 0.0925 (8) O3 0.3313 (5) 0.65999 (15) 0.35320 (11) 0.0827 (7) O4 0.4211 (4) 0.71868 (12) 0.24860 (11) 0.0664 (6) N1 0.9495 (5) 0.83212 (18) 0.44323 (13) 0.0661 (7) C1 1.0658 (6) 0.8888 (2) 0.39946 (17) 0.0604 (8) C2 0.9964 (5) 0.88958 (18) 0.32672 (15) 0.0529 (7) C3 0.7966 (5) 0.83108 (18) 0.30156 (14) 0.0522 (7)

H3 0.7449 0.8310 0.2536 0.063*

C4 0.6733 (5) 0.77302 (17) 0.34672 (14) 0.0500 (7) C5 0.7594 (6) 0.7747 (2) 0.41872 (15) 0.0611 (8) C6 1.2721 (7) 0.9495 (2) 0.43497 (17) 0.0836 (11)

H6A 1.1845 1.0041 0.4363 0.125*

H6B 1.4497 0.9521 0.4086 0.125*

H6C 1.3136 0.9310 0.4826 0.125*

C7 0.6517 (8) 0.7147 (2) 0.47389 (16) 0.0934 (12)

H7A 0.7351 0.7289 0.5194 0.140*

H7B 0.7076 0.6586 0.4614 0.140*

H7C 0.4433 0.7180 0.4763 0.140*

C8 1.1295 (7) 0.9500 (2) 0.27714 (18) 0.0662 (8)

C9 1.126 (4) 0.9914 (10) 0.1507 (9) 0.090 (6) 0.39 (2)

H9A 1.2256 1.0415 0.1675 0.108* 0.39 (2)

H9B 0.9473 1.0075 0.1265 0.108* 0.39 (2)

C10 1.321 (5) 0.9396 (10) 0.1025 (8) 0.114 (6) 0.39 (2)

H10A 1.4833 0.9184 0.1295 0.171* 0.39 (2)

H10B 1.3903 0.9741 0.0644 0.171* 0.39 (2)

H10C 1.2112 0.8935 0.0830 0.171* 0.39 (2)

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H9′1 1.4378 0.9824 0.1682 0.100* 0.61 (2)

H9′2 1.1710 1.0448 0.1646 0.100* 0.61 (2)

C10′ 1.145 (4) 0.9524 (8) 0.0878 (3) 0.119 (4) 0.61 (2)

H10D 1.2066 0.8950 0.0844 0.178* 0.61 (2)

H10E 1.2384 0.9848 0.0515 0.178* 0.61 (2)

H10F 0.9381 0.9556 0.0816 0.178* 0.61 (2)

C11 0.4586 (6) 0.71134 (19) 0.31846 (16) 0.0554 (7) C12 0.2205 (6) 0.6604 (2) 0.21440 (16) 0.0700 (9)

H12A 0.0285 0.6654 0.2349 0.084*

H12B 0.2879 0.6032 0.2208 0.084*

C13 0.2095 (10) 0.6817 (3) 0.13845 (18) 0.1354 (18)

H13A 0.1485 0.7389 0.1329 0.203*

H13B 0.0736 0.6454 0.1144 0.203*

H13C 0.3992 0.6747 0.1184 0.203*

Atomic displacement parameters (Å2₎

U11 _U22 _U33 _U12 _U13 _U23

O1 0.118 (2) 0.0879 (19) 0.121 (2) −0.0455 (17) −0.0152 (17) 0.0054 (16) O2 0.122 (2) 0.0816 (17) 0.0740 (16) −0.0377 (15) 0.0253 (14) 0.0011 (13) O3 0.0925 (16) 0.0773 (16) 0.0786 (15) −0.0218 (13) 0.0083 (12) 0.0090 (13) O4 0.0680 (13) 0.0658 (14) 0.0653 (13) −0.0154 (11) −0.0060 (10) −0.0022 (11) N1 0.0579 (15) 0.0766 (19) 0.0637 (16) 0.0063 (15) −0.0078 (13) −0.0050 (15) C1 0.0455 (16) 0.063 (2) 0.072 (2) 0.0135 (16) −0.0071 (15) −0.0170 (18) C2 0.0418 (15) 0.0491 (18) 0.068 (2) 0.0066 (14) 0.0023 (14) −0.0030 (16) C3 0.0454 (15) 0.0553 (18) 0.0560 (17) 0.0093 (15) 0.0026 (13) −0.0044 (15) C4 0.0424 (14) 0.0507 (18) 0.0569 (17) 0.0064 (14) 0.0035 (13) −0.0031 (15) C5 0.0544 (17) 0.067 (2) 0.062 (2) 0.0136 (17) 0.0015 (15) −0.0007 (17) C6 0.069 (2) 0.089 (3) 0.093 (2) −0.002 (2) −0.0165 (18) −0.032 (2) C7 0.107 (3) 0.110 (3) 0.063 (2) −0.013 (2) −0.0012 (19) 0.019 (2) C8 0.0581 (19) 0.056 (2) 0.084 (2) 0.0019 (17) 0.0035 (17) −0.0088 (19) C9 0.081 (8) 0.092 (8) 0.098 (9) −0.029 (7) 0.008 (6) 0.008 (6) C10 0.115 (9) 0.116 (8) 0.112 (8) 0.007 (7) 0.034 (7) 0.006 (7) C9′ 0.090 (6) 0.077 (5) 0.084 (5) −0.016 (5) 0.019 (4) 0.008 (4) C10′ 0.148 (8) 0.121 (7) 0.088 (5) −0.027 (6) 0.019 (5) 0.018 (5) C11 0.0520 (17) 0.0531 (19) 0.061 (2) 0.0084 (15) 0.0055 (15) 0.0030 (16) C12 0.0620 (18) 0.065 (2) 0.083 (2) −0.0094 (17) −0.0056 (16) −0.0150 (18) C13 0.169 (4) 0.155 (4) 0.081 (3) −0.071 (4) −0.042 (3) 0.005 (3)

Geometric parameters (Å, º)

O1—C8 1.198 (3) C7—H7A 0.9600

O2—C8 1.322 (3) C7—H7B 0.9600

O2—C9′ 1.473 (7) C7—H7C 0.9600

O2—C9 1.476 (9) C9—C10 1.525 (10)

O3—C11 1.203 (3) C9—H9A 0.9700

O4—C11 1.328 (3) C9—H9B 0.9700

N1—C5 1.344 (4) C10—H10C 0.9600

C1—C2 1.400 (4) C9′—C10′ 1.508 (8)

C1—C6 1.505 (4) C9′—H9′1 0.9700

C2—C3 1.388 (4) C9′—H9′2 0.9700

C2—C8 1.478 (4) C10′—H10D 0.9600

C3—C4 1.382 (4) C10′—H10E 0.9600

C3—H3 0.9300 C10′—H10F 0.9600

C4—C5 1.406 (4) C12—C13 1.468 (4)

C4—C11 1.487 (4) C12—H12A 0.9700

C5—C7 1.499 (4) C12—H12B 0.9700

C6—H6A 0.9600 C13—H13A 0.9600

C6—H6B 0.9600 C13—H13B 0.9600

C6—H6C 0.9600 C13—H13C 0.9600

C8—O2—C9′ 112.8 (4) O2—C8—C2 112.7 (3)

C8—O2—C9 123.5 (10) O2—C9—C10 102.4 (8)

C9′—O2—C9 19.9 (9) O2—C9—H9A 111.3

C11—O4—C12 117.1 (2) C10—C9—H9A 111.3

C1—N1—C5 120.8 (3) O2—C9—H9B 111.3

N1—C1—C2 121.2 (3) C10—C9—H9B 111.3

N1—C1—C6 114.6 (3) H9A—C9—H9B 109.2

C2—C1—C6 124.2 (3) O2—C9′—C10′ 103.6 (6)

C3—C2—C1 118.0 (3) O2—C9′—H9′1 111.0

C3—C2—C8 120.0 (3) C10′—C9′—H9′1 111.0

C1—C2—C8 122.0 (3) O2—C9′—H9′2 111.0

C4—C3—C2 121.0 (3) C10′—C9′—H9′2 111.0

C4—C3—H3 119.5 H9′1—C9′—H9′2 109.0

C2—C3—H3 119.5 C9′—C10′—H10D 109.5

C3—C4—C5 117.8 (3) C9′—C10′—H10E 109.5

C3—C4—C11 119.9 (3) H10D—C10′—H10E 109.5

C5—C4—C11 122.3 (3) C9′—C10′—H10F 109.5

N1—C5—C4 121.2 (3) H10D—C10′—H10F 109.5

N1—C5—C7 114.6 (3) H10E—C10′—H10F 109.5

C4—C5—C7 124.2 (3) O3—C11—O4 122.6 (3)

C1—C6—H6A 109.5 O3—C11—C4 125.5 (3)

C1—C6—H6B 109.5 O4—C11—C4 111.9 (3)

H6A—C6—H6B 109.5 O4—C12—C13 107.3 (3)

C1—C6—H6C 109.5 O4—C12—H12A 110.3

H6A—C6—H6C 109.5 C13—C12—H12A 110.3

H6B—C6—H6C 109.5 O4—C12—H12B 110.3

C5—C7—H7A 109.5 C13—C12—H12B 110.3

C5—C7—H7B 109.5 H12A—C12—H12B 108.5

H7A—C7—H7B 109.5 C12—C13—H13A 109.5

C5—C7—H7C 109.5 C12—C13—H13B 109.5

H7A—C7—H7C 109.5 H13A—C13—H13B 109.5

H7B—C7—H7C 109.5 C12—C13—H13C 109.5

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O1—C8—C2 125.9 (3) H13B—C13—H13C 109.5

C5—N1—C1—C2 −0.8 (4) C9′—O2—C8—C2 −173.1 (7) C5—N1—C1—C6 179.3 (2) C9—O2—C8—C2 167.9 (8)

N1—C1—C2—C3 1.8 (4) C3—C2—C8—O1 170.6 (3)

C6—C1—C2—C3 −178.4 (3) C1—C2—C8—O1 −9.6 (5) N1—C1—C2—C8 −178.1 (3) C3—C2—C8—O2 −9.1 (4)

C6—C1—C2—C8 1.8 (4) C1—C2—C8—O2 170.7 (3)

C1—C2—C3—C4 −1.0 (4) C8—O2—C9—C10 123.2 (17) C8—C2—C3—C4 178.8 (2) C9′—O2—C9—C10 61 (2) C2—C3—C4—C5 −0.7 (4) C8—O2—C9′—C10′ 176.0 (12) C2—C3—C4—C11 179.7 (2) C9—O2—C9′—C10′ −57 (2) C1—N1—C5—C4 −1.0 (4) C12—O4—C11—O3 −1.1 (4) C1—N1—C5—C7 179.1 (3) C12—O4—C11—C4 178.7 (2) C3—C4—C5—N1 1.7 (4) C3—C4—C11—O3 −177.5 (3) C11—C4—C5—N1 −178.6 (2) C5—C4—C11—O3 2.9 (4) C3—C4—C5—C7 −178.4 (3) C3—C4—C11—O4 2.8 (3) C11—C4—C5—C7 1.2 (4) C5—C4—C11—O4 −176.9 (2) C9′—O2—C8—O1 7.2 (8) C11—O4—C12—C13 178.7 (3) C9—O2—C8—O1 −11.8 (9)

Hydrogen-bond geometry (Å, º)

D—H···A D—H H···A D···A D—H···A

C12—H12B···O1i _{0.97 2.52 3.346 (4) 143}