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Acta Crystallographica Section E: Structure Reports Online logoLink to Acta Crystallographica Section E: Structure Reports Online
. 2011 Oct 5;67(Pt 11):o2820. doi: 10.1107/S1600536811039626

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

Juanjuan Zheng a, Xueyuan Wang b, Dongying Pang b, Yan Sun c, Wei Su c,*
PMCID: PMC3247561  PMID: 22219866

Abstract

The title compound, C17H16N2O6, is a decomposition product of the hypertension drug nifedipine [systematic name: dimethyl 2,6-dimethyl-4-(2-nitro­phen­yl)-1,4-dihydro­pyridine-3,5-dicarboxyl­ate]. The dihedral angle between the nitro­sophenyl ring and the pyridine ring is 67.1 (5)°.

Related literature

For the calcium antagonistic activity of compounds of the 1,4-dihydro­pyridine class, which inhibit the influx of Ca2+ ions through plasma membrane channels, see: Núnez-Vergara et al. (1994 ▶) and for their current use in the treatment of a variety of cardiovascular disorders such as angina and hypertension, see: Triggle et al. (1989 ▶); Hurwitz et al. (1991 ▶). For general background to derivatives of the dihydropyridine calcium channel blockers nifedipine [3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate] and nisoldpine [isobutyl methyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate], see: Chen et al. (2010 ▶); Rowan & Holt (1996 ▶, 1997a ▶,b ▶); Schultheiss et al. (2010 ▶). For standard bond lengths, see: Allen et al. (1987 ▶). graphic file with name e-67-o2820-scheme1.jpg

Experimental

Crystal data

  • C17H16N2O6

  • M r = 344.32

  • Triclinic, Inline graphic

  • a = 7.578 (4) Å

  • b = 8.141 (4) Å

  • c = 14.235 (9) Å

  • α = 103.32 (2)°

  • β = 93.75 (5)°

  • γ = 105.39 (3)°

  • V = 816.4 (8) Å3

  • Z = 2

  • Mo Kα radiation

  • μ = 0.11 mm−1

  • T = 298 K

  • 0.20 × 0.18 × 0.12 mm

Data collection

  • Rigaku Saturn724 CCD diffractometer

  • Absorption correction: multi-scan (CrystalClear; Rigaku, 2005 ▶) T min = 0.979, T max = 0.987

  • 8658 measured reflections

  • 3843 independent reflections

  • 2247 reflections with I > 2σ(I)

  • R int = 0.047

Refinement

  • R[F 2 > 2σ(F 2)] = 0.038

  • wR(F 2) = 0.097

  • S = 1.03

  • 3843 reflections

  • 230 parameters

  • H-atom parameters constrained

  • Δρmax = 0.21 e Å−3

  • Δρmin = −0.29 e Å−3

Data collection: CrystalClear (Rigaku, 2005 ▶); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: CrystalStructure (Rigaku, 2005 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811039626/qm2031sup1.cif

e-67-o2820-sup1.cif (22.6KB, cif)

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811039626/qm2031Isup2.hkl

e-67-o2820-Isup2.hkl (188.4KB, hkl)

Supplementary material file. DOI: 10.1107/S1600536811039626/qm2031Isup3.cml

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

Acknowledgments

This study was supported by the Tianjin Natural Science Foundation (10JCZDJC23900).

supplementary crystallographic information

Comment

Compounds of the 1,4-dihydropyridine class exhibit calcium antagonistic activity, as they inhibit the influx of Ca2+ ions through plasma membrane channels (Núnez-Vergara, Sunkel & Squella, 1994). Compounds of this class are currently being used in the treatment of a variety of cardiovascular disorders, such as angina and hypertension (Triggle et al., 1989; Hurwitz et al., 1991). Nifedipine [dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate], is the best known member of this class. The molecular structure of (I) is shown in Fig. 1. The bond lengths and angles are within normal ranges (Allen et al., 1987). The dihedral angle between the nitrosophenyl ring and the pyridine ring is 67.1°.

Experimental

The title compound was prepared by adding following steps. 1: Add 1 g nifedipine and 10 g (NH4)2S2O8 to the 100 ml acetone solution(50%). 2: Stir for 12 h at 30 °C.3:Regulate the solution to pH=8 with Na2CO3. The resulting solution was extracted with methylene chloride. The organic layer was dried over MgSO4 and evaporated under reduced pressure. Following washing the extract with water, crystals of suitable size for single-crystal analysis were recrystallized from methanol.

Refinement

H atoms were positioned geometrically, with C—H = 0.93 and 0.96 A ° for aromatic and methyl H atoms, respectively, and constrained to ride on their parent atoms, with Uiso(H) = xUeq(C), where x = 1.2 for aromatic and x = 1.5 for methyl H atoms.

Figures

Fig. 1.

Fig. 1.

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[3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)pyridine-3,5-dicarboxylate]

Crystal data

C17H16N2O6 Z = 2
Mr = 344.32 F(000) = 360
Triclinic, P1 Dx = 1.401 Mg m−3
a = 7.578 (4) Å Mo Kα radiation, λ = 0.71073 Å
b = 8.141 (4) Å Cell parameters from 2919 reflections
c = 14.235 (9) Å θ = 1.5–28.0°
α = 103.32 (2)° µ = 0.11 mm−1
β = 93.75 (5)° T = 298 K
γ = 105.39 (3)° Prism, yellow
V = 816.4 (8) Å3 0.20 × 0.18 × 0.12 mm
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Data collection

Rigaku Saturn724 CCD diffractometer 3843 independent reflections
Radiation source: rotating anode 2247 reflections with I > 2σ(I)
multilayer Rint = 0.047
Detector resolution: 14.22 pixels mm-1 θmax = 27.9°, θmin = 1.5°
ω and φ scans h = −9→9
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005) k = −10→10
Tmin = 0.979, Tmax = 0.987 l = −18→17
8658 measured reflections
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Refinement

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)] = 0.038 Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.097 H-atom parameters constrained
S = 1.03 w = 1/[σ2(Fo2) + (0.028P)2] where P = (Fo2 + 2Fc2)/3
3843 reflections (Δ/σ)max = 0.001
230 parameters Δρmax = 0.21 e Å−3
0 restraints Δρmin = −0.29 e Å−3
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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.
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Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

x y z Uiso*/Ueq
O1 0.76803 (15) 0.93198 (15) 0.92024 (8) 0.0333 (3)
O2 0.84798 (13) 0.68996 (14) 0.85050 (7) 0.0240 (3)
O3 0.40716 (15) 0.78829 (15) 0.70787 (8) 0.0344 (3)
O4 0.63979 (19) 0.91761 (16) 0.64507 (10) 0.0520 (4)
O5 0.13443 (14) 0.30250 (15) 0.61801 (7) 0.0279 (3)
O6 0.18628 (14) 0.11367 (14) 0.70271 (7) 0.0259 (3)
N1 0.26875 (17) 0.55143 (17) 0.95102 (9) 0.0218 (3)
N2 0.54570 (19) 0.78817 (18) 0.66853 (9) 0.0283 (3)
C1 0.5124 (2) 0.7905 (2) 1.05399 (10) 0.0256 (4)
H1A 0.4799 0.8996 1.0549 0.038*
H1B 0.6471 0.8165 1.0651 0.038*
H1C 0.4582 0.7401 1.1054 0.038*
C2 0.4386 (2) 0.6606 (2) 0.95644 (10) 0.0200 (3)
C3 0.53855 (19) 0.65051 (19) 0.87679 (10) 0.0184 (3)
C4 0.45649 (19) 0.52477 (19) 0.78913 (10) 0.0175 (3)
C5 0.2806 (2) 0.4125 (2) 0.78490 (10) 0.0188 (3)
C6 0.1892 (2) 0.4295 (2) 0.86757 (11) 0.0200 (3)
C7 −0.0011 (2) 0.3140 (2) 0.86810 (11) 0.0278 (4)
H7A 0.0077 0.2160 0.8954 0.042*
H7B −0.0653 0.2675 0.8013 0.042*
H7C −0.0701 0.3832 0.9080 0.042*
C8 0.7278 (2) 0.7743 (2) 0.88633 (11) 0.0214 (3)
C9 1.0316 (2) 0.8018 (2) 0.84997 (12) 0.0297 (4)
H9A 1.0228 0.8948 0.8183 0.045*
H9B 1.1038 0.7310 0.8141 0.045*
H9C 1.0925 0.8554 0.9171 0.045*
C10 0.55534 (18) 0.50220 (19) 0.70104 (10) 0.0176 (3)
C11 0.6085 (2) 0.3487 (2) 0.67264 (10) 0.0226 (4)
H11 0.5774 0.2612 0.7077 0.027*
C12 0.7059 (2) 0.3213 (2) 0.59432 (11) 0.0267 (4)
H12 0.7401 0.2154 0.5759 0.032*
C13 0.7538 (2) 0.4482 (2) 0.54255 (11) 0.0263 (4)
H13 0.8218 0.4296 0.4893 0.032*
C14 0.7024 (2) 0.6014 (2) 0.56854 (11) 0.0237 (4)
H14 0.7342 0.6887 0.5334 0.028*
C15 0.60384 (19) 0.6254 (2) 0.64663 (10) 0.0202 (3)
C16 0.19127 (19) 0.2747 (2) 0.69257 (11) 0.0200 (3)
C17 0.1122 (2) −0.0294 (2) 0.61593 (12) 0.0364 (4)
H17A −0.0139 −0.0318 0.5937 0.055*
H17B 0.1105 −0.1415 0.6307 0.055*
H17C 0.1898 −0.0116 0.5646 0.055*
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Atomic displacement parameters (Å2)

U11 U22 U33 U12 U13 U23
O1 0.0287 (7) 0.0182 (6) 0.0483 (8) 0.0042 (5) 0.0079 (5) 0.0014 (6)
O2 0.0200 (6) 0.0216 (6) 0.0293 (6) 0.0058 (5) 0.0056 (5) 0.0041 (5)
O3 0.0382 (7) 0.0388 (8) 0.0381 (7) 0.0221 (6) 0.0167 (6) 0.0170 (6)
O4 0.0680 (10) 0.0273 (8) 0.0727 (10) 0.0148 (7) 0.0355 (8) 0.0278 (8)
O5 0.0279 (6) 0.0343 (7) 0.0211 (6) 0.0059 (5) 0.0023 (5) 0.0102 (5)
O6 0.0320 (6) 0.0194 (6) 0.0223 (6) 0.0061 (5) −0.0008 (5) 0.0004 (5)
N1 0.0245 (7) 0.0220 (7) 0.0214 (7) 0.0086 (6) 0.0074 (5) 0.0072 (6)
N2 0.0376 (9) 0.0251 (8) 0.0255 (8) 0.0098 (7) 0.0069 (6) 0.0111 (7)
C1 0.0318 (9) 0.0260 (9) 0.0212 (8) 0.0119 (8) 0.0040 (7) 0.0058 (7)
C2 0.0248 (8) 0.0195 (8) 0.0188 (8) 0.0109 (7) 0.0036 (6) 0.0057 (7)
C3 0.0200 (8) 0.0168 (8) 0.0211 (8) 0.0080 (7) 0.0040 (6) 0.0065 (7)
C4 0.0205 (8) 0.0173 (8) 0.0188 (8) 0.0094 (7) 0.0062 (6) 0.0072 (7)
C5 0.0210 (8) 0.0190 (8) 0.0188 (8) 0.0077 (7) 0.0052 (6) 0.0066 (7)
C6 0.0222 (8) 0.0190 (8) 0.0217 (8) 0.0082 (7) 0.0065 (6) 0.0072 (7)
C7 0.0247 (9) 0.0281 (10) 0.0287 (9) 0.0048 (8) 0.0119 (7) 0.0045 (8)
C8 0.0248 (8) 0.0223 (9) 0.0176 (8) 0.0074 (7) 0.0039 (6) 0.0051 (7)
C9 0.0192 (8) 0.0312 (10) 0.0363 (10) 0.0029 (7) 0.0059 (7) 0.0085 (8)
C10 0.0131 (7) 0.0195 (8) 0.0170 (8) 0.0008 (6) 0.0016 (6) 0.0034 (6)
C11 0.0219 (8) 0.0213 (9) 0.0241 (9) 0.0054 (7) 0.0041 (7) 0.0055 (7)
C12 0.0244 (9) 0.0258 (9) 0.0285 (9) 0.0101 (8) 0.0054 (7) 0.0005 (8)
C13 0.0201 (8) 0.0334 (10) 0.0210 (9) 0.0047 (8) 0.0067 (6) 0.0012 (8)
C14 0.0207 (8) 0.0276 (9) 0.0194 (8) 0.0001 (7) 0.0039 (6) 0.0071 (7)
C15 0.0185 (8) 0.0193 (8) 0.0207 (8) 0.0034 (7) 0.0023 (6) 0.0036 (7)
C16 0.0142 (7) 0.0234 (9) 0.0231 (9) 0.0041 (7) 0.0080 (6) 0.0073 (7)
C17 0.0424 (11) 0.0262 (10) 0.0303 (10) 0.0072 (9) −0.0033 (8) −0.0074 (8)
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Geometric parameters (Å, °)

O1—C8 1.2086 (18) C5—C16 1.498 (2)
O2—C8 1.3392 (18) C6—C7 1.500 (2)
O2—C9 1.4485 (18) C7—H7A 0.9800
O3—N2 1.2218 (16) C7—H7B 0.9800
O4—N2 1.2349 (16) C7—H7C 0.9800
O5—C16 1.2107 (18) C9—H9A 0.9800
O6—C16 1.3427 (19) C9—H9B 0.9800
O6—C17 1.4481 (19) C9—H9C 0.9800
N1—C2 1.342 (2) C10—C15 1.393 (2)
N1—C6 1.344 (2) C10—C11 1.394 (2)
N2—C15 1.478 (2) C11—C12 1.385 (2)
C1—C2 1.506 (2) C11—H11 0.9500
C1—H1A 0.9800 C12—C13 1.388 (2)
C1—H1B 0.9800 C12—H12 0.9500
C1—H1C 0.9800 C13—C14 1.381 (2)
C2—C3 1.403 (2) C13—H13 0.9500
C3—C4 1.401 (2) C14—C15 1.385 (2)
C3—C8 1.495 (2) C14—H14 0.9500
C4—C5 1.390 (2) C17—H17A 0.9800
C4—C10 1.502 (2) C17—H17B 0.9800
C5—C6 1.402 (2) C17—H17C 0.9800
C8—O2—C9 115.40 (13) O2—C8—C3 111.74 (14)
C16—O6—C17 115.28 (12) O2—C9—H9A 109.5
C2—N1—C6 120.11 (13) O2—C9—H9B 109.5
O3—N2—O4 123.19 (15) H9A—C9—H9B 109.5
O3—N2—C15 118.96 (13) O2—C9—H9C 109.5
O4—N2—C15 117.85 (14) H9A—C9—H9C 109.5
C2—C1—H1A 109.5 H9B—C9—H9C 109.5
C2—C1—H1B 109.5 C15—C10—C11 116.86 (13)
H1A—C1—H1B 109.5 C15—C10—C4 125.17 (14)
C2—C1—H1C 109.5 C11—C10—C4 117.94 (13)
H1A—C1—H1C 109.5 C12—C11—C10 121.28 (15)
H1B—C1—H1C 109.5 C12—C11—H11 119.4
N1—C2—C3 121.69 (15) C10—C11—H11 119.4
N1—C2—C1 114.91 (13) C11—C12—C13 120.22 (15)
C3—C2—C1 123.39 (14) C11—C12—H12 119.9
C4—C3—C2 118.72 (14) C13—C12—H12 119.9
C4—C3—C8 121.45 (13) C14—C13—C12 119.93 (14)
C2—C3—C8 119.83 (14) C14—C13—H13 120.0
C5—C4—C3 118.81 (13) C12—C13—H13 120.0
C5—C4—C10 118.94 (14) C13—C14—C15 118.90 (15)
C3—C4—C10 122.20 (13) C13—C14—H14 120.5
C4—C5—C6 119.36 (14) C15—C14—H14 120.5
C4—C5—C16 119.84 (13) C14—C15—C10 122.80 (15)
C6—C5—C16 120.80 (14) C14—C15—N2 116.56 (14)
N1—C6—C5 121.30 (14) C10—C15—N2 120.61 (13)
N1—C6—C7 116.40 (13) O5—C16—O6 123.94 (15)
C5—C6—C7 122.30 (14) O5—C16—C5 125.59 (15)
C6—C7—H7A 109.5 O6—C16—C5 110.45 (13)
C6—C7—H7B 109.5 O6—C17—H17A 109.5
H7A—C7—H7B 109.5 O6—C17—H17B 109.5
C6—C7—H7C 109.5 H17A—C17—H17B 109.5
H7A—C7—H7C 109.5 O6—C17—H17C 109.5
H7B—C7—H7C 109.5 H17A—C17—H17C 109.5
O1—C8—O2 123.61 (15) H17B—C17—H17C 109.5
O1—C8—C3 124.63 (14)
C6—N1—C2—C3 −0.6 (2) C5—C4—C10—C15 115.28 (17)
C6—N1—C2—C1 −179.75 (12) C3—C4—C10—C15 −67.4 (2)
N1—C2—C3—C4 1.1 (2) C5—C4—C10—C11 −66.86 (18)
C1—C2—C3—C4 −179.85 (13) C3—C4—C10—C11 110.45 (17)
N1—C2—C3—C8 −179.70 (13) C15—C10—C11—C12 0.4 (2)
C1—C2—C3—C8 −0.7 (2) C4—C10—C11—C12 −177.67 (14)
C2—C3—C4—C5 −1.2 (2) C10—C11—C12—C13 0.4 (2)
C8—C3—C4—C5 179.60 (13) C11—C12—C13—C14 −0.7 (2)
C2—C3—C4—C10 −178.56 (13) C12—C13—C14—C15 0.2 (2)
C8—C3—C4—C10 2.3 (2) C13—C14—C15—C10 0.6 (2)
C3—C4—C5—C6 0.9 (2) C13—C14—C15—N2 −177.47 (13)
C10—C4—C5—C6 178.33 (13) C11—C10—C15—C14 −0.9 (2)
C3—C4—C5—C16 −178.88 (13) C4—C10—C15—C14 176.99 (14)
C10—C4—C5—C16 −1.5 (2) C11—C10—C15—N2 177.12 (13)
C2—N1—C6—C5 0.3 (2) C4—C10—C15—N2 −5.0 (2)
C2—N1—C6—C7 −179.65 (13) O3—N2—C15—C14 152.38 (14)
C4—C5—C6—N1 −0.5 (2) O4—N2—C15—C14 −27.0 (2)
C16—C5—C6—N1 179.35 (13) O3—N2—C15—C10 −25.7 (2)
C4—C5—C6—C7 179.50 (13) O4—N2—C15—C10 154.89 (15)
C16—C5—C6—C7 −0.7 (2) C17—O6—C16—O5 1.9 (2)
C9—O2—C8—O1 −3.1 (2) C17—O6—C16—C5 −176.59 (11)
C9—O2—C8—C3 175.45 (12) C4—C5—C16—O5 −70.6 (2)
C4—C3—C8—O1 131.12 (17) C6—C5—C16—O5 109.63 (18)
C2—C3—C8—O1 −48.0 (2) C4—C5—C16—O6 107.95 (15)
C4—C3—C8—O2 −47.44 (18) C6—C5—C16—O6 −71.86 (17)
C2—C3—C8—O2 133.40 (14)
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Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: QM2031).

References

  1. Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19.
  2. Chen, H., Qu, D., Wang, Q.-F. & Jiang, R. (2010). Acta Cryst. E66, o619. [DOI] [PMC free article] [PubMed]
  3. Hurwitz, L., Partridge, L. D. & Leach, J. K. (1991). In Calcium Channels: Their Properties, Functions, Regulation and Clinical Relevance Boca Raton, Florida, USA: CRC Press.
  4. Núnez-Vergara, L. J., Sunkel, C. & Squella, J. A. (1994). J. Pharm. Sci. 83, 502–507. [DOI] [PubMed]
  5. Rigaku (2005). CrystalClear and CrystalStructure Rigaku Corporation, Tokyo, Japan.
  6. Rowan, K. R. & Holt, E. M. (1996). Acta Cryst. C52, 1565–1570.
  7. Rowan, K. R. & Holt, E. M. (1997a). Acta Cryst. C53, 106–108.
  8. Rowan, K. R. & Holt, E. M. (1997b). Acta Cryst. C53, 257–261.
  9. Schultheiss, N., Roe, M. & Smit, J. P. (2010). Acta Cryst. E66, o2297–o2298. [DOI] [PMC free article] [PubMed]
  10. Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [DOI] [PubMed]
  11. Triggle, D. J., Langs, D. A. & Janis, R. A. (1989). Med. Res. Rev. 9, 123–180. [DOI] [PubMed]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811039626/qm2031sup1.cif

e-67-o2820-sup1.cif (22.6KB, cif)

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811039626/qm2031Isup2.hkl

e-67-o2820-Isup2.hkl (188.4KB, hkl)

Supplementary material file. DOI: 10.1107/S1600536811039626/qm2031Isup3.cml

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

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography

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