Diethyl 4-(4-ethoxy­phen­yl)-2,6-dimethyl-1,4-dihydro­pyridine-3,5-dicarboxyl­ate

Hoong-Kun Fun; Jia Hao Goh; B Palakshi Reddy; S Sarveswari; V Vijayakumar

doi:10.1107/S160053680903339X

. 2009 Aug 26;65(Pt 9):o2247–o2248. doi: 10.1107/S160053680903339X

Diethyl 4-(4-ethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate

Hoong-Kun Fun ^a,^*,^‡, Jia Hao Goh ^a, B Palakshi Reddy ^b, S Sarveswari ^b, V Vijayakumar ^b

PMCID: PMC2969936 PMID: 21577645

Abstract

In the title compound, C₂₁H₂₇NO₅, the dihydropyridine ring adopts a boat conformation. The ethoxyphenyl ring is oriented approximately perpendicular to the planar part of the dihydropyridine ring, making a dihedral angle of 89.45 (6)°. An intramolecular C—H⋯O hydrogen bond generates an S(6) ring motif. In the crystal structure, neighbouring molecules are linked into chains along the a axis by N—H⋯O hydrogen bonds and the chains are interconnected into two-dimensional networks parallel to the ab plane by C—H⋯O hydrogen bonds. The structure is further stabilized by weak C—H⋯π interactions.

Related literature

For general background to and applications of 1,4-dihydropyridine derivatives, see: Böcker & Guengerich (1986 ▶); Cooper et al. (1992 ▶); Vo et al. (1995 ▶); Gaudio et al. (1994 ▶); Gordeev et al. (1996 ▶); Sunkel et al. (1992 ▶). For ring conformations and ring puckering analysis, see: Boeyens (1978 ▶); Cremer & Pople (1975 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). For bond-length data, see: Allen et al. (1987 ▶). For a related structure, see: Thenmozhi et al. (2009 ▶). For the stability of the temperature controller used for the data collection, see: Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C₂₁H₂₇NO₅
M _r = 373.44
Triclinic,
a = 7.5557 (1) Å
b = 9.5697 (1) Å
c = 14.0553 (2) Å
α = 85.844 (1)°
β = 87.679 (1)°
γ = 81.458 (1)°
V = 1001.91 (2) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 296 K
0.28 × 0.27 × 0.07 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2005 ▶) T _min = 0.976, T _max = 0.994
20664 measured reflections
5290 independent reflections
3602 reflections with I > 2σ(I)
R _int = 0.027

Refinement

R[F ² > 2σ(F ²)] = 0.055
wR(F ²) = 0.161
S = 1.02
5290 reflections
253 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.24 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 2005 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053680903339X/ci2893sup1.cif

e-65-o2247-sup1.cif^{(22.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053680903339X/ci2893Isup2.hkl

e-65-o2247-Isup2.hkl^{(259KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N1⋯O2ⁱ	0.85 (2)	2.18 (2)	3.0045 (19)	165 (2)
C12—H12A⋯O4ⁱⁱ	0.97	2.51	3.458 (2)	166
C20—H20A⋯O3	0.96	2.14	2.7774 (19)	122
C16—H16A⋯Cg1ⁱⁱⁱ	0.96	2.83	3.767 (2)	165

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) . Cg1 is the centroid of the C1–C6 benzene ring.

Acknowledgments

HKF and JHG thank Universiti Sains Malaysia (USM) for the Research University Golden Goose grant (No. 1001/PFIZIK/811012). JHG also thanks USM for the award of a USM fellowship. VV is grateful to DST–India for funding through the Young Scientist Scheme (Fast Track Proposal).

supplementary crystallographic information

Comment

Hantzsch 1,4-dihydropyridines (1,4-DHPS) are biologically active compounds which includes various vasodilator, anti-hypertensive, bronchodilator, heptaprotective, anti-tumor, anti-mutagenic, geroprotective and anti-diabetic agents (Gaudio et al., 1994). Nifedipine, nitrendipine and nimodipine have found commercial utility as calcium channel blockers (Böcker et al., 1986; Gordeev et al., 1996). For the treatment of congestive heart failure, a number of DHP calcium antagonists have been introduced (Sunkel et al., 1992; Vo et al., 1995). Some of DHPs have been introduced as a neuroprotectant and cognition enhancer. In addition, a number of DHPs with platelet anti-aggregatory activity have also been discovered (Cooper et al., 1992).

In the title compound (Fig. 1), the dihydropyridine ring adopts a boat conformation (Boeyens, 1978; Cremer & Pople, 1975) with puckering amplitude Q = 0.2994 (16) Å, θ = 73.0 (3)° and φ = 181.7 (3)°. Atoms C7 and N1 deviate from the C8/C9/C10/C11 plane by 0.362 (2) and 0.143 (2) Å, respectively. The C1-C6 benzene ring is perpendicular to the C8-C11 plane, making a dihedral angle of 89.45 (6)°. An intramolecular C20—H20A···O3 hydrogen bond generates an S(6) ring motif (Bernstein et al., 1995). Bond lengths (Allen et al., 1987) and angles are comparable to a related structure (Thenmozhi et al., 2009).

In the crystal structure (Fig. 2), neighbouring molecules are linked into chains along the a-axis by N1—H1N1···O2 hydrogen bonds (Table 1). These chains are interconnected into two-dimensional networks parallel to the ab plane by C12—H12A···O4 hydrogen bonds. The crystal structure is further stabilized by weak C16—H16A···Cg1 interactions (Table 1).

Experimental

The title compound was prepared according to Hantzsch pyridine synthesis. A mixture of 4-ethoxybenzaldehyde (10 mmol), ethylacetoacetate (20 mmol) and ammonium acetate (10 mmol) were heated at 353 K for 3 h (monitored by TLC). After completion of the reaction, the mixture was cooled to room temperature and kept for 2 days to get the solid product. The solid formed was washed using diethyl ether. After washing, the solid and the liquid was collected separately and the liquid was kept for solidification. The purity of the crude product was checked through TLC and recrystallized using acetone and ether (m.p. 377–379 K).