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Acta Crystallogr Sect E Struct Rep Online. 2008 January 1; 64(Pt 1): o293.
Published online 2007 December 18. doi:  10.1107/S1600536807063428
PMCID: PMC2915344

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

Abstract

The title compound, C18H19NO5, is a product of the Hantzsch reaction of p-phthalaldehyde, methyl acetoacetate, and ammonium acetate. The 1,4-dihydro­pyridine ring of the mol­ecule adopts a flattened boat conformation. The benzene ring is almost perpendicular to the 1,4-dihydro­pyridine ring; the plane through the six C atoms of the benzene ring and the plane through the four C atoms that form the base of the boat-shaped 1,4-dihydro­pyridine ring (excluding the ring N atom and the opposite ring C atom) make a dihedral angle of 87.60 (3)°. Inter­molecular N—H(...)O hydrogen bonds result in the formation of extended chains along the a axis.

Related literature

For a related 1,4-dihydro­pyridine structure, see: Fossheim et al. (1982 [triangle]). For the synthesis of 1,4-dihydro­pyridines, see: Hantzsch & Liebigs (1882 [triangle]). For the biological activity of 1,4-dihydro­pyridines, see: Janis & Triggle (1983 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-64-0o293-scheme1.jpg

Experimental

Crystal data

  • C18H19NO5
  • M r = 329.34
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-0o293-efi1.jpg
  • a = 8.219 (2) Å
  • b = 10.432 (3) Å
  • c = 10.979 (3) Å
  • α = 111.364 (3)°
  • β = 102.799 (3)°
  • γ = 101.150 (4)°
  • V = 815.0 (4) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.10 mm−1
  • T = 298 (2) K
  • 0.48 × 0.34 × 0.10 mm

Data collection

  • Bruker SMART CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS: Sheldrick, 2004 [triangle]) T min = 0.954, T max = 0.990
  • 4173 measured reflections
  • 2855 independent reflections
  • 2352 reflections with I > 2σ(I)
  • R int = 0.015

Refinement

  • R[F 2 > 2σ(F 2)] = 0.052
  • wR(F 2) = 0.140
  • S = 1.04
  • 2855 reflections
  • 221 parameters
  • H-atom parameters constrained
  • Δρmax = 0.25 e Å−3
  • Δρmin = −0.23 e Å−3

Data collection: SMART (Bruker, 2001 [triangle]); cell refinement: SAINT (Bruker, 2001 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1990 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2001 [triangle]); software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536807063428/sq2008sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536807063428/sq2008Isup2.hkl

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

Acknowledgments

The authors are grateful to Dr Jianping Ma of Shandong Normal University for his help with the crystallographic analysis.

supplementary crystallographic information

Comment

It is well known that 1,4-dihydropyridines (DHPs) exhibit a wide range of biological activities, acting as potent vasodilators and antihypertensives (Janis & Triggle, 1983). The classical preparation method of 1,4-dihydropyridines is the Hantzsch reaction (Hantzsch & Liebigs, 1882). We have synthesized a series of 1,4-dihydropyridine compounds by the Hantzsch protocol in water. The structure of (I) was fully characterized by NMR (1H,13C), MS, IR, and elemental analysis and was confirmed by single-crystal X-ray crystallographic analysis (Figure 1).

The bond lengths and angles in (I) show normal values (Table 1) except for the geometry of the 1,4-dihydropyridine ring which adopts a flattened boat conformation with ring distortions at the nitrogen (Nl) and the tetrahedral carbon (C11). Both atoms are displaced to the same side of the ring with distances of 0.17Å and 0.39 Å, respectively, from the plane defined by C3, C4, C7, and C8, and thus form the apices of a boat-type conformation (Fossheim et al., 1982). The phenyl ring is almost perpendicular to the 1,4-dihydropyridine ring (N1—C4—C3—C11—C8—C7) with a dihedral angle of 92.40 (1)°. The bisect plane of the 1,4-dihydropyridine ring defined by N1, C11, and C12 makes a dihedral angle of 35.40 (7)° with the phenyl ring. The intermolecular hydrogen bonds N1—H1···O5i [symmetry code (i): -x + 1, -y + 2, -z + 2] between the pyridine N atom and a neighboring formyl O atom result in the formation of extended chains along the a axis (Figure 2).

Experimental

The title compound,(I), was prepared by refluxing a mixture of p-phthaldehyde (0.67 g, 5.0 mmol), methyl acetoacetate (1.19 g, 10.25 mmol), and ammonium acetate (0.58 g, 7.5 mmol) for 6 h in water (10 ml), and purified by recrystallization, m.p.479–481 K. Single crystals suitable for X-ray diffraction were obtained by slow evaporation of an ethyl acetate solution.

Refinement

All non-hydrogen atoms were refined with anisotropic displacement parameters. Hydrogen atoms attached to anisotropically refined atoms were placed in geometrically idealized positions and included as riding atoms with C—H = 0.93Å and Uiso(H) = 1.2*Ueq(C) (aromatic); C—H = 0.96Å and Uiso(H) = 1.5*Ueq(C) (methyl); C—H = 0.98Å and Uiso(H) = 1.2*Ueq(C) (tertiary CH).

Figures

Fig. 1.
The crystal structure drawing for (I) with the atom-numbering scheme and ellipsoids shown at the 50% probability level.
Fig. 2.
The crystal packing diagram for (I). Hydrogen bonds are shown as dashed lines.

Crystal data

C18H19NO5Z = 2
Mr = 329.34F000 = 348
Triclinic, P1Dx = 1.342 Mg m3
Hall symbol: -P 1Melting point: 479 K
a = 8.219 (2) ÅMo Kα radiation λ = 0.71073 Å
b = 10.432 (3) ÅCell parameters from 1572 reflections
c = 10.979 (3) Åθ = 2.2–26.7º
α = 111.364 (3)ºµ = 0.10 mm1
β = 102.799 (3)ºT = 298 (2) K
γ = 101.150 (4)ºPlate, colourless
V = 815.0 (4) Å30.48 × 0.34 × 0.10 mm

Data collection

Bruker SMART CCD area-detector diffractometer2855 independent reflections
Radiation source: fine-focus sealed tube2352 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.015
T = 298(2) Kθmax = 25.1º
phi and ω scansθmin = 2.1º
Absorption correction: multi-scan(SADABS: Sheldrick, 2004)h = −7→9
Tmin = 0.954, Tmax = 0.990k = −12→12
4173 measured reflectionsl = −13→11

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.052H-atom parameters constrained
wR(F2) = 0.140  w = 1/[σ2(Fo2) + (0.0745P)2 + 0.2263P] where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max < 0.001
2855 reflectionsΔρmax = 0.25 e Å3
221 parametersΔρmin = −0.23 e Å3
Primary atom site location: structure-invariant direct methodsExtinction correction: none

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
C10.0487 (3)0.7111 (3)0.2379 (2)0.0540 (6)
H1A0.16630.75270.24290.081*
H1B−0.02630.75980.20530.081*
H1C0.00870.61050.17530.081*
C20.1597 (3)0.6835 (2)0.4429 (2)0.0369 (5)
C30.1430 (2)0.7146 (2)0.58051 (19)0.0316 (4)
C40.2082 (3)0.6488 (2)0.6575 (2)0.0360 (5)
C50.3136 (3)0.5473 (2)0.6249 (3)0.0501 (6)
H5A0.29390.50480.52720.075*
H5B0.27920.47270.65380.075*
H5C0.43550.59890.67250.075*
C6−0.0172 (3)0.7028 (3)0.9224 (3)0.0562 (6)
H6A−0.02660.79130.98530.084*
H6B0.06930.67300.97070.084*
H6C−0.12820.62940.88450.084*
C70.0357 (3)0.7258 (2)0.8083 (2)0.0369 (5)
C8−0.0337 (2)0.7922 (2)0.73481 (19)0.0326 (4)
C9−0.1879 (3)0.8380 (2)0.7515 (2)0.0403 (5)
C10−0.3909 (3)0.9447 (3)0.6724 (3)0.0648 (7)
H10A−0.48830.86090.64360.097*
H10B−0.41260.99010.61100.097*
H10C−0.37591.01130.76460.097*
C110.0538 (2)0.8272 (2)0.63858 (18)0.0298 (4)
H11−0.03690.82350.56140.036*
C120.1873 (2)0.9776 (2)0.70850 (19)0.0306 (4)
C130.2279 (3)1.0506 (2)0.6300 (2)0.0352 (5)
H130.16951.00930.53560.042*
C140.3539 (3)1.1837 (2)0.6906 (2)0.0387 (5)
H140.37971.23100.63680.046*
C150.4421 (2)1.2473 (2)0.8316 (2)0.0360 (5)
C160.5802 (3)1.3855 (2)0.8933 (2)0.0443 (5)
H160.59431.43290.83740.053*
C170.4002 (3)1.1764 (2)0.9107 (2)0.0423 (5)
H170.45761.21861.00540.051*
C180.2739 (3)1.0439 (2)0.8499 (2)0.0395 (5)
H180.24610.99810.90440.047*
O10.2601 (3)0.6284 (2)0.39502 (18)0.0686 (5)
O20.0449 (2)0.72623 (17)0.37188 (14)0.0483 (4)
O3−0.23540 (19)0.90263 (18)0.66944 (17)0.0504 (4)
O4−0.2703 (2)0.8207 (2)0.8252 (2)0.0747 (6)
O50.6775 (2)1.44321 (17)1.01131 (17)0.0562 (5)
N10.1702 (2)0.67213 (19)0.77876 (18)0.0412 (4)
H10.23350.65230.83890.049*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0704 (16)0.0601 (15)0.0303 (12)0.0144 (12)0.0190 (11)0.0191 (11)
C20.0353 (10)0.0365 (11)0.0348 (11)0.0084 (9)0.0136 (9)0.0106 (9)
C30.0284 (9)0.0344 (10)0.0300 (10)0.0073 (8)0.0094 (8)0.0126 (8)
C40.0324 (10)0.0351 (10)0.0359 (11)0.0063 (8)0.0084 (8)0.0136 (9)
C50.0477 (13)0.0487 (13)0.0603 (15)0.0223 (11)0.0167 (11)0.0264 (12)
C60.0671 (16)0.0706 (16)0.0500 (14)0.0234 (13)0.0269 (12)0.0401 (13)
C70.0367 (11)0.0396 (11)0.0322 (11)0.0063 (9)0.0105 (9)0.0158 (9)
C80.0303 (10)0.0386 (11)0.0272 (10)0.0072 (8)0.0098 (8)0.0134 (8)
C90.0353 (11)0.0498 (12)0.0351 (11)0.0104 (9)0.0154 (9)0.0162 (10)
C100.0452 (14)0.0819 (19)0.088 (2)0.0365 (13)0.0322 (14)0.0428 (16)
C110.0283 (9)0.0377 (10)0.0242 (9)0.0097 (8)0.0084 (8)0.0140 (8)
C120.0305 (10)0.0353 (10)0.0307 (10)0.0144 (8)0.0129 (8)0.0151 (8)
C130.0385 (11)0.0391 (11)0.0297 (10)0.0129 (9)0.0097 (8)0.0166 (9)
C140.0419 (11)0.0422 (12)0.0427 (12)0.0157 (9)0.0182 (9)0.0255 (10)
C150.0329 (10)0.0365 (11)0.0408 (11)0.0133 (8)0.0139 (9)0.0162 (9)
C160.0418 (12)0.0413 (12)0.0522 (14)0.0134 (10)0.0155 (11)0.0219 (11)
C170.0429 (12)0.0461 (12)0.0304 (11)0.0070 (9)0.0097 (9)0.0126 (9)
C180.0436 (12)0.0438 (12)0.0301 (11)0.0060 (9)0.0127 (9)0.0177 (9)
O10.0757 (12)0.0995 (15)0.0529 (11)0.0537 (12)0.0386 (10)0.0324 (10)
O20.0566 (9)0.0688 (10)0.0300 (8)0.0290 (8)0.0194 (7)0.0240 (7)
O30.0424 (9)0.0688 (11)0.0632 (11)0.0303 (8)0.0285 (8)0.0392 (9)
O40.0658 (12)0.1291 (18)0.0740 (13)0.0490 (12)0.0508 (11)0.0651 (13)
O50.0491 (9)0.0482 (9)0.0542 (11)0.0042 (8)0.0013 (8)0.0173 (8)
N10.0425 (10)0.0499 (11)0.0385 (10)0.0177 (8)0.0100 (8)0.0266 (8)

Geometric parameters (Å, °)

C1—O21.429 (2)C9—O41.203 (2)
C1—H1A0.9600C9—O31.344 (2)
C1—H1B0.9600C10—O31.432 (3)
C1—H1C0.9600C10—H10A0.9600
C2—O11.202 (2)C10—H10B0.9600
C2—O21.337 (3)C10—H10C0.9600
C2—C31.469 (3)C11—C121.529 (3)
C3—C41.355 (3)C11—H110.9800
C3—C111.522 (3)C12—C181.390 (3)
C4—N11.381 (3)C12—C131.394 (3)
C4—C51.489 (3)C13—C141.381 (3)
C5—H5A0.9600C13—H130.9300
C5—H5B0.9600C14—C151.389 (3)
C5—H5C0.9600C14—H140.9300
C6—C71.495 (3)C15—C171.386 (3)
C6—H6A0.9600C15—C161.463 (3)
C6—H6B0.9600C16—O51.211 (3)
C6—H6C0.9600C16—H160.9300
C7—C81.346 (3)C17—C181.378 (3)
C7—N11.381 (3)C17—H170.9300
C8—C91.463 (3)C18—H180.9300
C8—C111.511 (2)N1—H10.8600
O2—C1—H1A109.5O3—C10—H10B109.5
O2—C1—H1B109.5H10A—C10—H10B109.5
H1A—C1—H1B109.5O3—C10—H10C109.5
O2—C1—H1C109.5H10A—C10—H10C109.5
H1A—C1—H1C109.5H10B—C10—H10C109.5
H1B—C1—H1C109.5C8—C11—C3110.09 (15)
O1—C2—O2121.76 (19)C8—C11—C12112.69 (15)
O1—C2—C3127.5 (2)C3—C11—C12109.55 (15)
O2—C2—C3110.72 (16)C8—C11—H11108.1
C4—C3—C2121.94 (18)C3—C11—H11108.1
C4—C3—C11119.60 (17)C12—C11—H11108.1
C2—C3—C11118.44 (16)C18—C12—C13118.16 (18)
C3—C4—N1118.15 (18)C18—C12—C11121.69 (16)
C3—C4—C5127.55 (19)C13—C12—C11120.14 (16)
N1—C4—C5114.27 (17)C14—C13—C12120.86 (18)
C4—C5—H5A109.5C14—C13—H13119.6
C4—C5—H5B109.5C12—C13—H13119.6
H5A—C5—H5B109.5C13—C14—C15120.34 (18)
C4—C5—H5C109.5C13—C14—H14119.8
H5A—C5—H5C109.5C15—C14—H14119.8
H5B—C5—H5C109.5C17—C15—C14119.14 (19)
C7—C6—H6A109.5C17—C15—C16121.20 (19)
C7—C6—H6B109.5C14—C15—C16119.65 (19)
H6A—C6—H6B109.5O5—C16—C15125.3 (2)
C7—C6—H6C109.5O5—C16—H16117.4
H6A—C6—H6C109.5C15—C16—H16117.4
H6B—C6—H6C109.5C18—C17—C15120.34 (19)
C8—C7—N1118.71 (17)C18—C17—H17119.8
C8—C7—C6126.71 (19)C15—C17—H17119.8
N1—C7—C6114.59 (18)C17—C18—C12121.13 (18)
C7—C8—C9121.16 (17)C17—C18—H18119.4
C7—C8—C11119.69 (17)C12—C18—H18119.4
C9—C8—C11119.07 (16)C2—O2—C1118.39 (17)
O4—C9—O3121.06 (19)C9—O3—C10116.16 (17)
O4—C9—C8127.2 (2)C7—N1—C4123.31 (16)
O3—C9—C8111.71 (16)C7—N1—H1118.3
O3—C10—H10A109.5C4—N1—H1118.3
O1—C2—C3—C4−18.6 (3)C8—C11—C12—C1827.1 (2)
O2—C2—C3—C4161.80 (17)C3—C11—C12—C18−95.8 (2)
O1—C2—C3—C11159.8 (2)C8—C11—C12—C13−154.35 (17)
O2—C2—C3—C11−19.8 (2)C3—C11—C12—C1382.7 (2)
C2—C3—C4—N1−172.96 (17)C18—C12—C13—C141.6 (3)
C11—C3—C4—N18.7 (3)C11—C12—C13—C14−177.05 (17)
C2—C3—C4—C54.6 (3)C12—C13—C14—C15−0.2 (3)
C11—C3—C4—C5−173.75 (19)C13—C14—C15—C17−1.0 (3)
N1—C7—C8—C9173.70 (18)C13—C14—C15—C16177.53 (18)
C6—C7—C8—C9−6.5 (3)C17—C15—C16—O56.6 (3)
N1—C7—C8—C11−9.5 (3)C14—C15—C16—O5−171.9 (2)
C6—C7—C8—C11170.29 (19)C14—C15—C17—C180.7 (3)
C7—C8—C9—O4−1.9 (3)C16—C15—C17—C18−177.79 (19)
C11—C8—C9—O4−178.8 (2)C15—C17—C18—C120.7 (3)
C7—C8—C9—O3179.69 (18)C13—C12—C18—C17−1.8 (3)
C11—C8—C9—O32.8 (3)C11—C12—C18—C17176.73 (18)
C7—C8—C11—C331.4 (2)O1—C2—O2—C1−2.8 (3)
C9—C8—C11—C3−151.73 (17)C3—C2—O2—C1176.83 (18)
C7—C8—C11—C12−91.2 (2)O4—C9—O3—C10−1.8 (3)
C9—C8—C11—C1285.7 (2)C8—C9—O3—C10176.73 (19)
C4—C3—C11—C8−31.0 (2)C8—C7—N1—C4−17.3 (3)
C2—C3—C11—C8150.61 (16)C6—C7—N1—C4162.9 (2)
C4—C3—C11—C1293.5 (2)C3—C4—N1—C717.6 (3)
C2—C3—C11—C12−84.9 (2)C5—C4—N1—C7−160.32 (19)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1···O5i0.862.273.107 (2)163

Symmetry codes: (i) −x+1, −y+2, −z+2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: SQ2008).

References

  • Bruker. (2001). SMART and SAINT Bruker AXS Inc., Madison, Wisconsin, USA.
  • Fossheim, R., Svarteng, K. & Mostad, A. (1982). J. Med. Chem 25, 126–131. [PubMed]
  • Hantzsch, A. & Liebigs, J. (1882). Ann. Chem 215, 1–82.
  • Janis, R. A. & Triggle, D. J. (1983). J. Med. Chem 25, 775–785. [PubMed]
  • Sheldrick, G. M. (1990). Acta Cryst. A46, 467–473.
  • Sheldrick, G. M. (1997). SHELXL97 University of Göttingen, Germany. [PubMed]
  • Sheldrick, G. M. (2001). SHELXTL Version 5.0. Bruker AXS Inc., Madison, Wisconsin, USA.
  • Sheldrick, G. M. (2004). SADABS University of Göttingen, Germany.

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