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Acta Crystallogr Sect E Struct Rep Online. 2010 January 1; 66(Pt 1): o86.
Published online 2009 December 9. doi:  10.1107/S1600536809051988
PMCID: PMC2980128

3-Isobutyl 5-methyl 2,6-dimethyl-4-(2-nitro­phen­yl)pyridine-3,5-dicarboxyl­ate

Abstract

The title nitro­phenyl pyridine compound, C20H22N2O6 was synthesized as a degradation product of the hypertension medication nisoldipine. The dihedral angle between the nitro-substituted phenyl ring and the pyridine ring is 75.5 (4)°. There are a number of C—H(...)O inter­actions between symmetry-related mol­ecules>.

Related literature

For the preparation of the title compound see: Agbaba et al. (2004 [triangle]); Waldo & Correa (2001 [triangle]); Valentina et al. (2000 [triangle]). A derivative of the title compound, nisoldipine, has been evaluated as a calcium channel blocker with vasodilator properties, see: Ferrari et al. (2005 [triangle]); Marciniec et al. (2002 [triangle]); Kazda et al. (1980 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-00o86-scheme1.jpg

Experimental

Crystal data

  • C20H22N2O6
  • M r = 386.40
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-00o86-efi1.jpg
  • a = 8.4222 (9) Å
  • b = 16.5850 (16) Å
  • c = 14.5011 (15) Å
  • β = 102.748 (2)°
  • V = 1975.6 (4) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.10 mm−1
  • T = 296 K
  • 0.12 × 0.10 × 0.08 mm

Data collection

  • Bruker APEXII CCD diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2001 [triangle]) T min = 0.989, T max = 0.992
  • 10199 measured reflections
  • 3683 independent reflections
  • 2718 reflections with I > 2σ(I)
  • R int = 0.020

Refinement

  • R[F 2 > 2σ(F 2)] = 0.046
  • wR(F 2) = 0.154
  • S = 1.01
  • 3683 reflections
  • 259 parameters
  • H-atom parameters constrained
  • Δρmax = 0.28 e Å−3
  • Δρmin = −0.21 e Å−3

Data collection: APEX2 (Bruker, 2004 [triangle]); cell refinement: SAINT-Plus (Bruker, 2001 [triangle]); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I. DOI: 10.1107/S1600536809051988/pk2213sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809051988/pk2213Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

We thank the Natural Science Foundation of China (Nos. 30901883, 20972189) for financial support.

supplementary crystallographic information

Comment

Nisoldipine is a calcium channel blocker with vasodilator properties (Marciniec et al. 2002). It is used in several commercial preparations for treatment of hypertension (Kazda et al. 1980). It has been the subject of many analytical chemical investigations. Synthetic conditions result in side-reactions and formation of 1,4-dihydropyridines. This compound is a degradation product of nisoldipine.

The molecular structure is shown in Fig 1. The dihedral angle between the planes of phenyl and the pyridyl rings is 75.5 (4)°. There are a number of C—H···O interactions between symmetry-related molecules.

Experimental

A solution of nisoldipine (10 mmol) in 50 mL anhydrous ethanol was exposed to sunlight for 10 h at ambient temperature. 50 mL of water was added to the mixture and it was then filtered. The crude product was purified by flash chromatography (40/60 ethyl acetate/ether).

Refinement

H-atoms were included in calculated positions and treated as riding atoms: C—H = 0.92—0.96 Å with with Uiso(H) = 1.2Ueq(C) or 1.5 Ueq(CMe)

Figures

Fig. 1.
Molecular structure of the title compound. Displacement ellipsoids are drawn at the 30% probability level.

Crystal data

C20H22N2O6F(000) = 816
Mr = 386.40Dx = 1.299 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 3360 reflections
a = 8.4222 (9) Åθ = 2.5–25.3°
b = 16.5850 (16) ŵ = 0.10 mm1
c = 14.5011 (15) ÅT = 296 K
β = 102.748 (2)°Block, colorless
V = 1975.6 (4) Å30.12 × 0.10 × 0.08 mm
Z = 4

Data collection

Bruker APEXII CCD diffractometer3683 independent reflections
Radiation source: fine-focus sealed tube2718 reflections with I > 2σ(I)
graphiteRint = 0.020
[var phi] and ω scansθmax = 25.5°, θmin = 1.9°
Absorption correction: multi-scan (SADABS; Bruker, 2001)h = −9→10
Tmin = 0.989, Tmax = 0.992k = −20→16
10199 measured reflectionsl = −17→14

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.046Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.154H-atom parameters constrained
S = 1.01w = 1/[σ2(Fo2) + (0.090P)2 + 0.3869P] where P = (Fo2 + 2Fc2)/3
3683 reflections(Δ/σ)max < 0.001
259 parametersΔρmax = 0.28 e Å3
0 restraintsΔρmin = −0.21 e Å3

Special details

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)

xyzUiso*/Ueq
C10.6743 (2)0.17497 (11)0.80315 (14)0.0478 (5)
C20.5729 (3)0.17694 (15)0.71437 (18)0.0685 (7)
H20.47640.14760.70200.082*
C30.6151 (4)0.22258 (17)0.64421 (17)0.0765 (8)
H30.54620.22500.58460.092*
C40.7583 (3)0.26433 (15)0.66227 (16)0.0700 (7)
H40.78770.29440.61450.084*
C50.8585 (3)0.26212 (12)0.75035 (15)0.0546 (5)
H50.95590.29070.76140.066*
C60.8188 (2)0.21826 (11)0.82405 (13)0.0412 (4)
C70.9348 (2)0.22295 (10)0.91819 (12)0.0376 (4)
C81.0480 (2)0.16259 (10)0.95138 (13)0.0403 (4)
C91.1657 (2)0.17571 (11)1.03476 (14)0.0443 (5)
C101.0622 (2)0.30249 (11)1.05295 (14)0.0457 (5)
C110.9444 (2)0.29486 (10)0.96861 (13)0.0396 (4)
C121.0756 (3)0.37681 (14)1.11321 (18)0.0692 (7)
H12A1.14410.36591.17410.104*
H12B0.96930.39231.12060.104*
H12C1.12190.41981.08340.104*
C131.2955 (3)0.11554 (13)1.07470 (17)0.0617 (6)
H13A1.37340.11321.03540.093*
H13B1.24710.06341.07680.093*
H13C1.34920.13151.13750.093*
C141.1842 (3)−0.01320 (15)0.8348 (2)0.0854 (9)
H14A1.1540−0.05370.87500.128*
H14B1.2928−0.02340.82720.128*
H14C1.1102−0.01470.77410.128*
C150.5685 (2)0.41210 (14)0.8841 (2)0.0660 (6)
H15A0.56110.41270.81640.079*
H15B0.60660.46460.90920.079*
C160.4058 (3)0.39528 (15)0.90375 (19)0.0657 (6)
H160.41790.39630.97250.079*
C170.2888 (3)0.46254 (19)0.8627 (2)0.0936 (9)
H17A0.33280.51340.88780.140*
H17B0.18590.45370.87920.140*
H17C0.27380.46300.79510.140*
C180.3416 (3)0.31309 (17)0.8696 (2)0.0772 (7)
H18A0.32920.31000.80230.116*
H18B0.23800.30460.88530.116*
H18C0.41670.27240.89940.116*
C191.0395 (2)0.08501 (11)0.89873 (15)0.0471 (5)
C200.8372 (2)0.36417 (11)0.93117 (14)0.0445 (4)
N10.62323 (19)0.12682 (11)0.87582 (15)0.0588 (5)
N21.16919 (19)0.24420 (10)1.08444 (12)0.0492 (4)
O10.9204 (2)0.04564 (10)0.87632 (16)0.0907 (7)
O21.17751 (19)0.06580 (9)0.87727 (13)0.0710 (5)
O30.68230 (15)0.34992 (8)0.92811 (11)0.0558 (4)
O40.88648 (19)0.42597 (9)0.90518 (15)0.0768 (5)
O50.6685 (2)0.14682 (11)0.95800 (12)0.0725 (5)
O60.5362 (2)0.06843 (12)0.85059 (16)0.0947 (6)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0388 (10)0.0479 (11)0.0536 (11)0.0019 (8)0.0038 (8)−0.0091 (9)
C20.0533 (13)0.0721 (15)0.0683 (16)0.0055 (11)−0.0123 (11)−0.0226 (13)
C30.092 (2)0.0798 (17)0.0451 (13)0.0281 (15)−0.0131 (12)−0.0107 (12)
C40.0932 (19)0.0689 (15)0.0452 (13)0.0206 (14)0.0095 (12)0.0037 (11)
C50.0598 (13)0.0534 (12)0.0503 (12)0.0046 (9)0.0114 (10)0.0032 (9)
C60.0401 (9)0.0398 (9)0.0419 (10)0.0058 (7)0.0055 (8)−0.0032 (8)
C70.0324 (9)0.0385 (9)0.0416 (10)−0.0045 (7)0.0076 (7)0.0009 (7)
C80.0373 (9)0.0349 (9)0.0481 (10)−0.0035 (7)0.0079 (8)0.0025 (8)
C90.0385 (9)0.0405 (10)0.0516 (11)−0.0036 (7)0.0048 (8)0.0042 (8)
C100.0406 (10)0.0438 (10)0.0505 (11)−0.0046 (8)0.0050 (8)−0.0062 (9)
C110.0322 (9)0.0383 (9)0.0489 (10)−0.0028 (7)0.0100 (8)−0.0006 (8)
C120.0661 (14)0.0570 (14)0.0759 (16)−0.0003 (11)−0.0032 (12)−0.0225 (12)
C130.0572 (13)0.0538 (13)0.0644 (14)0.0057 (10)−0.0074 (10)0.0045 (10)
C140.0797 (17)0.0593 (15)0.121 (2)0.0004 (13)0.0313 (16)−0.0361 (15)
C150.0462 (12)0.0578 (13)0.0916 (17)0.0121 (10)0.0101 (11)0.0198 (12)
C160.0487 (12)0.0741 (15)0.0734 (15)0.0114 (11)0.0116 (11)0.0161 (12)
C170.0564 (15)0.098 (2)0.124 (3)0.0277 (14)0.0160 (15)0.0310 (19)
C180.0513 (13)0.0931 (19)0.0862 (18)−0.0068 (13)0.0130 (12)0.0095 (15)
C190.0409 (10)0.0378 (10)0.0592 (12)−0.0002 (8)0.0035 (9)0.0003 (9)
C200.0402 (10)0.0391 (10)0.0533 (11)−0.0018 (8)0.0084 (8)−0.0020 (8)
N10.0403 (9)0.0596 (11)0.0751 (13)−0.0099 (8)0.0099 (9)−0.0080 (10)
N20.0433 (9)0.0479 (9)0.0512 (10)−0.0021 (7)−0.0010 (7)−0.0025 (7)
O10.0535 (9)0.0594 (10)0.1577 (19)−0.0133 (8)0.0201 (11)−0.0422 (11)
O20.0602 (9)0.0568 (9)0.1024 (13)−0.0086 (7)0.0317 (9)−0.0292 (8)
O30.0370 (7)0.0486 (8)0.0804 (10)0.0036 (6)0.0101 (7)0.0143 (7)
O40.0538 (9)0.0472 (9)0.1299 (16)0.0000 (7)0.0214 (9)0.0233 (9)
O50.0717 (11)0.0852 (12)0.0627 (11)−0.0205 (9)0.0197 (8)−0.0001 (9)
O60.0713 (11)0.0836 (13)0.1256 (17)−0.0391 (10)0.0141 (11)−0.0118 (11)

Geometric parameters (Å, °)

C1—C21.379 (3)C13—H13B0.9600
C1—C61.388 (3)C13—H13C0.9600
C1—N11.460 (3)C14—O21.454 (3)
C2—C31.376 (4)C14—H14A0.9600
C2—H20.9300C14—H14B0.9600
C3—C41.365 (4)C14—H14C0.9600
C3—H30.9300C15—O31.456 (2)
C4—C51.367 (3)C15—C161.486 (3)
C4—H40.9300C15—H15A0.9700
C5—C61.393 (3)C15—H15B0.9700
C5—H50.9300C16—C181.509 (4)
C6—C71.495 (2)C16—C171.521 (3)
C7—C111.392 (2)C16—H160.9800
C7—C81.393 (2)C17—H17A0.9600
C8—C91.401 (3)C17—H17B0.9600
C8—C191.490 (3)C17—H17C0.9600
C9—N21.342 (2)C18—H18A0.9600
C9—C131.499 (3)C18—H18B0.9600
C10—N21.332 (2)C18—H18C0.9600
C10—C111.400 (3)C19—O11.181 (2)
C10—C121.501 (3)C19—O21.307 (2)
C11—C201.488 (3)C20—O41.197 (2)
C12—H12A0.9600C20—O31.317 (2)
C12—H12B0.9600N1—O61.221 (2)
C12—H12C0.9600N1—O51.214 (2)
C13—H13A0.9600
C2—C1—C6121.6 (2)H13B—C13—H13C109.5
C2—C1—N1117.79 (19)O2—C14—H14A109.5
C6—C1—N1120.59 (17)O2—C14—H14B109.5
C3—C2—C1119.7 (2)H14A—C14—H14B109.5
C3—C2—H2120.2O2—C14—H14C109.5
C1—C2—H2120.2H14A—C14—H14C109.5
C4—C3—C2119.9 (2)H14B—C14—H14C109.5
C4—C3—H3120.0O3—C15—C16109.20 (18)
C2—C3—H3120.0O3—C15—H15A109.8
C3—C4—C5120.2 (2)C16—C15—H15A109.8
C3—C4—H4119.9O3—C15—H15B109.8
C5—C4—H4119.9C16—C15—H15B109.8
C4—C5—C6121.8 (2)H15A—C15—H15B108.3
C4—C5—H5119.1C15—C16—C18112.7 (2)
C6—C5—H5119.1C15—C16—C17109.4 (2)
C1—C6—C5116.75 (18)C18—C16—C17112.3 (2)
C1—C6—C7126.24 (17)C15—C16—H16107.4
C5—C6—C7117.00 (17)C18—C16—H16107.4
C11—C7—C8118.55 (16)C17—C16—H16107.4
C11—C7—C6118.36 (15)C16—C17—H17A109.5
C8—C7—C6122.52 (15)C16—C17—H17B109.5
C7—C8—C9119.11 (16)H17A—C17—H17B109.5
C7—C8—C19119.47 (16)C16—C17—H17C109.5
C9—C8—C19121.41 (16)H17A—C17—H17C109.5
N2—C9—C8121.50 (16)H17B—C17—H17C109.5
N2—C9—C13115.35 (17)C16—C18—H18A109.5
C8—C9—C13123.15 (17)C16—C18—H18B109.5
N2—C10—C11121.95 (17)H18A—C18—H18B109.5
N2—C10—C12116.00 (17)C16—C18—H18C109.5
C11—C10—C12122.05 (17)H18A—C18—H18C109.5
C7—C11—C10118.98 (16)H18B—C18—H18C109.5
C7—C11—C20120.65 (16)O1—C19—O2123.08 (19)
C10—C11—C20120.30 (16)O1—C19—C8124.05 (19)
C10—C12—H12A109.5O2—C19—C8112.84 (16)
C10—C12—H12B109.5O4—C20—O3123.53 (18)
H12A—C12—H12B109.5O4—C20—C11123.49 (17)
C10—C12—H12C109.5O3—C20—C11112.97 (15)
H12A—C12—H12C109.5O6—N1—O5123.3 (2)
H12B—C12—H12C109.5O6—N1—C1118.1 (2)
C9—C13—H13A109.5O5—N1—C1118.68 (17)
C9—C13—H13B109.5C10—N2—C9119.82 (16)
H13A—C13—H13B109.5C19—O2—C14116.10 (18)
C9—C13—H13C109.5C20—O3—C15116.05 (15)
H13A—C13—H13C109.5

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C12—H12C···O4i0.962.573.303 (3)134
C13—H13B···O1ii0.962.483.395 (3)160
C14—H14B···O6iii0.962.523.221 (3)130

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: PK2213).

References

  • Agbaba, D., Vucicevic, K. & Marinkovic, V. (2004). Chromatographia, 60, 223–227.
  • Bruker (2001). SADABS and SAINT-Plus Bruker AXS Inc., Madison, Wisconsin, USA.
  • Bruker (2004). APEX2 Bruker AXS Inc., Madison, Wisconsin, USA.
  • Ferrari, M., Ghezzi, M., Alberelli, C. & &Ambrosini, L. (2005). US Patent 2005/0240022 A1.
  • Kazda, S., Garhoff, B., Meyer, H., Schlossmann, K., Stoepel, K., Towart, R., Vater, W. & Wehinger, E. (1980). Arzneim. Forsch. Drug Res.30, 2144–2162. [PubMed]
  • Marciniec, B., Jaroszkiewicz, E. & Ogrodowczyk, M. (2002). Int. J. Pharm.233, 207–215. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Valentina, M., Danica, A., Katarina, K. R., Jozef, C. & &Dobrila, Z. S. (2000). Farmaco, 55, 128–133.
  • Waldo, H. & Correa, J. L. S. (2001). Green Chem.3, 296–301.

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