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Acta Crystallogr Sect E Struct Rep Online. 2009 October 1; 65(Pt 10): o2390.
Published online 2009 September 9. doi:  10.1107/S1600536809035478
PMCID: PMC2970369

Dimethyl 2,6-dimethyl-1,4-dihydro­pyridine-3,5-dicarboxyl­ate

Abstract

In the crystal of the title compound, C11H15NO4, the mol­ecules are linked into sheets by N—H(...)O and C—H(...)O hydrogen bonds. Within the mol­ecule, the 1,4-dihydro­pyridine ring exhibits a distinctive planar conformation [r.m.s. deviation from the mean plane of 0.009 (3)Å], and the other non-H atoms are almost coplanar [r.m.s. deviation = 0.021 (3) Å] with the 1,4-dihydro­pyridine ring. The conformation of the latter is governed mainly by two intra­molecular C—H(...)O non-classical inter­actions.

Related literature

For general background to the biological activity of 1,4-dihydro­pyridine derivatives, see: Kazda & Towart (1981 [triangle]); Janis & Triggle (1983 [triangle]); Núñez-Vergara et al., (1998 [triangle]); Mak et al., (2002 [triangle]). For their synthesis, see: Hantzsch & Liebigs (1882 [triangle]). For related structures, see: Bai et al. (2009 [triangle]); Quesada et al. (2006 [triangle]); Ramesh et al. (2008 [triangle]); Zhao & Teng (2008 [triangle]). For hydrogen-bond motifs, see: Bernstein et al. (1995 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o2390-scheme1.jpg

Experimental

Crystal data

  • C11H15NO4
  • M r = 225.24
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o2390-efi1.jpg
  • a = 7.3933 (13) Å
  • b = 7.8391 (14) Å
  • c = 11.1847 (19) Å
  • α = 75.977 (2)°
  • β = 75.274 (2)°
  • γ = 64.351 (2)°
  • V = 558.62 (17) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.10 mm−1
  • T = 293 K
  • 0.49 × 0.43 × 0.25 mm

Data collection

  • Bruker SMART CCD diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 2003 [triangle]) T min = 0.952, T max = 0.965
  • 3550 measured reflections
  • 2047 independent reflections
  • 1764 reflections with I > 2σ(I)
  • R int = 0.015

Refinement

  • R[F 2 > 2σ(F 2)] = 0.040
  • wR(F 2) = 0.115
  • S = 1.05
  • 2047 reflections
  • 148 parameters
  • H-atom parameters constrained
  • Δρmax = 0.16 e Å−3
  • Δρmin = −0.23 e Å−3

Data collection: SMART (Bruker, 1997 [triangle]); cell refinement: SAINT (Bruker, 1997 [triangle]); data reduction: SAINT; 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, global. DOI: 10.1107/S1600536809035478/rk2162sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809035478/rk2162Isup2.hkl

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

Acknowledgments

This work was supported by the Innovation Scientists and Technicians Troop Construction Projects of Henan Province (2008IRTSTHN002). The authors are grateful to the Physiochemical Analysis Measurement Laboratory, College of Chemistry, Luoyang Normal University, for performing the X-ray analysis.

supplementary crystallographic information

Comment

The 1,4-dihydropyridine, (1,4-DHP) derivatives, as analogues of NADH coenzymes, exhibit a wide range of biological activities, acting as powerful arteriolar vasodilators (Kazda & Towart, 1981) and antihypertensives (Janis & Triggle, 1983). In addition, 1,4-DHP compounds such as nifedipine, nisoldipine and nicardipine exhibit potential trypanocidal activity (Núñez-Vergara et al., 1998). The classical preparation method of 1,4-DHP is the Hantzsch (Hantzsch & Liebigs, 1882) and a number of 1,4-DHP derivatives have been synthesized via this method. We have prepared some 1,4-DHP derivatives by condensation reaction of β-enamino esters with aldehyde. As a typical example containing a planar 1,4-DHP ring, we now report the molecular and supramolecular structure of dimethyl 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate, (I) (Fig. 1).

In the I, interestingly, 1,4-DHP ring exhibit perfectly coplanar conformation with r.m.s. deviation from the mean plane of 0.009 (3)Å. This conformation is significantly diverse from those found in other 1,4-DHP derivatives, where each of the 1,4-dihydropyrimidine rings adopts flat-boat conformation (Quesada et al., 2006; Ramesh, et al., 2008; Zhao & Teng, 2008; Bai et al., 2009). Another point of interest in the conformation concerns the ester portion of the molecule. In each molecule, there are two short non-classical intramolecular C–H···O interactions (Table 1), and these, we think, control and stabilize the conformations of the two methoxycarbonyl fragments, which are both coplanar with the 1,4-DHP ring, as shown by the torsion angles. However, for C2-methoxycarbonyl it is carbonyl atom O2 that participates in the intramolecular hydrogen bond, and for C4-methoxycarbonyl it is ethoxy O3 atom. Within the 1,4-DHP ring, the C1-C2 and C4-C5 distances shows markedly two double bonds. The N1–C1 and N1–C5 bonds are significantly shorter than the standard N–C experimental bond length of 1.47Å (Mak, et al., 2002). These features in bond distance suggest the existence of π-delocation in the C2/C1/N1/C5/C4 fragment.

Due to the above conformational features of I, its supramolecular structure exhibits some interesting feature. The molecules of the title compounds are linked into sheets by two independent intermolecular hydrogen bonds, one of N–H···O and one C–H···O type (Table 1), the formation of which is readily analyzed in terms of two one-dimensional substructures, one formed by the the N–H···O hydrogen bond and one formed by the C–H···O hydrogen bond. For the sake of simplicity, we shall omit any further consideration of other C–H···O intermolecular interaction involving C7-methyl group, which is too weak to influence the overall dimensionality of the supramolecular structure. In the first substructure, atom N1 in the molecule at (x, y, z) acts as a hydrogen-bond donor to the methoxycarbonyl atom O4 in the molecule at (x-1, y, z), thus forming by translation a C22(6) (Bernstein et al., 1995) chain running along the [1 0 0] direction (Fig. 2). In the second substructure, methyl atom C11 in the molecule at (x, y, z) acts as a hydrogen bond donor via H11B to methoxycarbonyl atom O2 in the milecule at (x+1, y, z-1), so forming by translation a C(9) (Bernstein et al., 1995) chain parallel to the [-1 0 1] direction (Fig. 2). The combination of the two chain motifs is sufficient to link all the molecules into a two-dimensional sheet parallel to (0 1 0). Two such sheets pass through each unit cell in the domains 0 < y < 1/2 and 1/2 < y < 1, and there are no direction-specific interactions between the two sheets.

Experimental

Into a three-necked round-bottomed flask equipped with a stirrer were introduced methyl 3-aminobut-2-enoate (0.1 mol, 11.5 g), aqueous formaldehyde (0.05 mol, 37% 4.0 g) and ethanol (95%, 25 ml). The resulted mixture was refluxed with stirring for ca 20 min, and then the solution is cooled to room temperature. The precipitate was filtered off, washed with cool ethanol (95%), and the resulting solid product was recrystallized from hot ethanol to give crystals of I.

1H NMR (DMSO, 400 MHz) of (I): δ 8.35 (s, 1H), δ 3.59 (s, 6H), δ 3.14 (s, 2H), δ 2.12 (s, 6H).

Refinement

All H atoms other than the C1- and C5-methyl H atoms were located in a difference map and then treated as riding atoms with C–H distances of 0.96Å (CH3) or 0.97Å (CH2), and N–H distance of 0.86Å with Uiso(H) = 1.2Ueq(C, N) or 1.5Ueq(methyl C). The C1- and C5-methyl H atoms was modelled as idealized disordered methyl groups over two sets offset by 60°.

Figures

Fig. 1.
The molecular structure of I, showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. H atoms are shown as small spheres of arbitrary radius. Only one component of the disordered methyl groups is shown.
Fig. 2.
Part of the crystal structure of I, showing the formation of a (0 1 0) sheet. For the sake of clarity, H atoms not involved in the motif shown have been omitted. Intermolecular interactions are represented by dashed lines. Symmetry codes: (i) x+1, y, ...

Crystal data

C11H15NO4Z = 2
Mr = 225.24F(000) = 240
Triclinic, P1Dx = 1.339 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 7.3933 (13) ÅCell parameters from 2071 reflections
b = 7.8391 (14) Åθ = 2.9–28.1°
c = 11.1847 (19) ŵ = 0.10 mm1
α = 75.977 (2)°T = 293 K
β = 75.274 (2)°Block, blue
γ = 64.351 (2)°0.49 × 0.43 × 0.25 mm
V = 558.62 (17) Å3

Data collection

Bruker SMART CCD diffractometer2047 independent reflections
Radiation source: fine-focus sealed tube1764 reflections with I > 2σ(I)
graphiteRint = 0.015
[var phi] and ω scansθmax = 25.5°, θmin = 2.9°
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)h = −8→8
Tmin = 0.952, Tmax = 0.965k = −9→9
3550 measured reflectionsl = −12→13

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.040H-atom parameters constrained
wR(F2) = 0.115w = 1/[σ2(Fo2) + (0.0612P)2 + 0.1212P] where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max < 0.001
2047 reflectionsΔρmax = 0.16 e Å3
148 parametersΔρmin = −0.23 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.26 (2)

Special details

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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*/UeqOcc. (<1)
C1−0.2092 (2)0.24631 (19)0.60198 (13)0.0371 (3)
C2−0.0517 (2)0.24220 (18)0.64524 (13)0.0355 (3)
C30.1441 (2)0.2394 (2)0.55870 (13)0.0366 (3)
H3A0.17020.34630.56770.044*
H3B0.25610.12240.58370.044*
C40.13729 (19)0.25116 (18)0.42266 (12)0.0328 (3)
C5−0.0262 (2)0.25369 (18)0.38665 (12)0.0348 (3)
C6−0.4103 (2)0.2499 (3)0.67563 (16)0.0519 (4)
H6A−0.49250.25280.62040.078*0.50
H6B−0.47870.36180.71610.078*0.50
H6C−0.38880.13740.73760.078*0.50
H6D−0.41420.24850.76230.078*0.50
H6E−0.42800.13960.66660.078*0.50
H6F−0.51780.36390.64520.078*0.50
C7−0.0548 (2)0.2638 (2)0.25662 (14)0.0467 (4)
H7A−0.18550.26330.25960.070*0.50
H7B0.05020.15530.22090.070*0.50
H7C−0.04740.37940.20620.070*0.50
H7D0.06370.26870.19820.070*0.50
H7E−0.17200.37670.23690.070*0.50
H7F−0.07440.15260.25160.070*0.50
C8−0.0642 (2)0.2376 (2)0.77872 (14)0.0430 (4)
C90.3211 (2)0.25935 (19)0.33790 (13)0.0359 (3)
C100.1095 (4)0.2341 (3)0.93016 (16)0.0699 (6)
H10A−0.00840.33840.96210.105*
H10B0.23030.24700.93580.105*
H10C0.10840.11520.97840.105*
C110.5033 (3)0.2757 (3)0.13100 (16)0.0647 (5)
H11A0.51800.39110.13200.097*
H11B0.49250.27200.04800.097*
H11C0.61990.16690.15630.097*
N1−0.19256 (17)0.24966 (18)0.47535 (11)0.0401 (3)
H1−0.29310.24920.45040.048*
O10.10679 (18)0.23698 (18)0.80131 (9)0.0537 (3)
O2−0.2029 (2)0.2326 (2)0.86306 (11)0.0705 (4)
O30.32231 (16)0.27138 (19)0.21605 (10)0.0547 (3)
O40.46494 (15)0.25501 (17)0.37415 (10)0.0499 (3)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0345 (7)0.0403 (7)0.0361 (7)−0.0168 (6)−0.0018 (6)−0.0055 (5)
C20.0353 (7)0.0396 (7)0.0318 (7)−0.0161 (6)−0.0029 (5)−0.0060 (5)
C30.0323 (7)0.0479 (8)0.0329 (7)−0.0183 (6)−0.0047 (5)−0.0082 (6)
C40.0314 (7)0.0376 (7)0.0307 (7)−0.0148 (5)−0.0047 (5)−0.0062 (5)
C50.0341 (7)0.0384 (7)0.0338 (7)−0.0161 (5)−0.0059 (5)−0.0052 (5)
C60.0397 (8)0.0718 (11)0.0470 (9)−0.0287 (7)0.0017 (7)−0.0108 (7)
C70.0443 (8)0.0679 (10)0.0366 (8)−0.0290 (7)−0.0102 (6)−0.0063 (7)
C80.0458 (8)0.0471 (8)0.0353 (8)−0.0201 (6)−0.0011 (6)−0.0077 (6)
C90.0329 (7)0.0415 (7)0.0341 (7)−0.0157 (6)−0.0052 (5)−0.0058 (5)
C100.0973 (15)0.0926 (14)0.0354 (9)−0.0492 (12)−0.0171 (9)−0.0088 (8)
C110.0512 (10)0.1089 (15)0.0386 (9)−0.0428 (10)0.0079 (7)−0.0144 (9)
N10.0324 (6)0.0575 (7)0.0369 (7)−0.0239 (5)−0.0061 (5)−0.0066 (5)
O10.0599 (7)0.0802 (8)0.0319 (6)−0.0359 (6)−0.0090 (5)−0.0106 (5)
O20.0668 (8)0.1125 (11)0.0357 (6)−0.0465 (8)0.0095 (6)−0.0153 (6)
O30.0457 (6)0.0966 (9)0.0316 (6)−0.0411 (6)0.0011 (4)−0.0101 (5)
O40.0356 (6)0.0772 (8)0.0430 (6)−0.0284 (5)−0.0049 (4)−0.0103 (5)

Geometric parameters (Å, °)

C1—C21.356 (2)C7—H7B0.9600
C1—N11.3848 (18)C7—H7C0.9600
C1—C61.4976 (19)C7—H7D0.9600
C2—C81.465 (2)C7—H7E0.9600
C2—C31.5172 (18)C7—H7F0.9600
C3—C41.5142 (18)C8—O21.2114 (19)
C3—H3A0.9700C8—O11.3489 (19)
C3—H3B0.9700C9—O41.2154 (17)
C4—C51.3587 (19)C9—O31.3411 (17)
C4—C91.4634 (18)C10—O11.4410 (19)
C5—N11.3771 (17)C10—H10A0.9600
C5—C71.5007 (19)C10—H10B0.9600
C6—H6A0.9600C10—H10C0.9600
C6—H6B0.9600C11—O31.4396 (18)
C6—H6C0.9600C11—H11A0.9600
C6—H6D0.9600C11—H11B0.9600
C6—H6E0.9600C11—H11C0.9600
C6—H6F0.9600N1—H10.8600
C7—H7A0.9600
C2—C1—N1119.37 (12)C5—C7—H7C109.5
C2—C1—C6127.69 (13)H7A—C7—H7C109.5
N1—C1—C6112.93 (12)H7B—C7—H7C109.5
C1—C2—C8120.67 (12)C5—C7—H7D109.5
C1—C2—C3121.77 (12)H7A—C7—H7D141.1
C8—C2—C3117.56 (12)H7B—C7—H7D56.3
C4—C3—C2112.94 (11)H7C—C7—H7D56.3
C4—C3—H3A109.0C5—C7—H7E109.5
C2—C3—H3A109.0H7A—C7—H7E56.3
C4—C3—H3B109.0H7B—C7—H7E141.1
C2—C3—H3B109.0H7C—C7—H7E56.3
H3A—C3—H3B107.8H7D—C7—H7E109.5
C5—C4—C9124.99 (12)C5—C7—H7F109.5
C5—C4—C3121.76 (12)H7A—C7—H7F56.3
C9—C4—C3113.25 (11)H7B—C7—H7F56.3
C4—C5—N1119.50 (12)H7C—C7—H7F141.1
C4—C5—C7127.93 (12)H7D—C7—H7F109.5
N1—C5—C7112.57 (11)H7E—C7—H7F109.5
C1—C6—H6A109.5O2—C8—O1121.07 (14)
C1—C6—H6B109.5O2—C8—C2127.86 (15)
H6A—C6—H6B109.5O1—C8—C2111.06 (12)
C1—C6—H6C109.5O4—C9—O3121.45 (12)
H6A—C6—H6C109.5O4—C9—C4122.90 (13)
H6B—C6—H6C109.5O3—C9—C4115.65 (11)
C1—C6—H6D109.5O1—C10—H10A109.5
H6A—C6—H6D141.1O1—C10—H10B109.5
H6B—C6—H6D56.3H10A—C10—H10B109.5
H6C—C6—H6D56.3O1—C10—H10C109.5
C1—C6—H6E109.5H10A—C10—H10C109.5
H6A—C6—H6E56.3H10B—C10—H10C109.5
H6B—C6—H6E141.1O3—C11—H11A109.5
H6C—C6—H6E56.3O3—C11—H11B109.5
H6D—C6—H6E109.5H11A—C11—H11B109.5
C1—C6—H6F109.5O3—C11—H11C109.5
H6A—C6—H6F56.3H11A—C11—H11C109.5
H6B—C6—H6F56.3H11B—C11—H11C109.5
H6C—C6—H6F141.1C5—N1—C1124.57 (11)
H6D—C6—H6F109.5C5—N1—H1117.7
H6E—C6—H6F109.5C1—N1—H1117.7
C5—C7—H7A109.5C8—O1—C10115.57 (13)
C5—C7—H7B109.5C9—O3—C11116.70 (12)
H7A—C7—H7B109.5
N1—C1—C2—C8−179.68 (12)C1—C2—C8—O1−179.05 (12)
C6—C1—C2—C81.0 (2)C3—C2—C8—O11.79 (18)
N1—C1—C2—C3−0.6 (2)C5—C4—C9—O4−179.32 (13)
C6—C1—C2—C3−179.85 (13)C3—C4—C9—O40.73 (19)
C1—C2—C3—C42.74 (19)C5—C4—C9—O30.4 (2)
C8—C2—C3—C4−178.11 (11)C3—C4—C9—O3−179.52 (11)
C2—C3—C4—C5−3.18 (18)C4—C5—N1—C11.1 (2)
C2—C3—C4—C9176.77 (11)C7—C5—N1—C1−177.92 (12)
C9—C4—C5—N1−178.51 (12)C2—C1—N1—C5−1.6 (2)
C3—C4—C5—N11.4 (2)C6—C1—N1—C5177.80 (12)
C9—C4—C5—C70.4 (2)O2—C8—O1—C10−1.3 (2)
C3—C4—C5—C7−179.65 (13)C2—C8—O1—C10179.51 (13)
C1—C2—C8—O21.8 (2)O4—C9—O3—C111.0 (2)
C3—C2—C8—O2−177.38 (15)C4—C9—O3—C11−178.77 (14)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1···O4i0.862.153.006 (2)176
C11—H11B···O2ii0.962.603.219 (2)122
C6—H6D···O20.962.092.843 (2)134
C7—H7D···O30.961.982.733 (2)134

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: RK2162).

References

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