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

Hoong-Kun Fun; Ching Kheng Quah; B Palakshi Reddy; S Sarveswari; V Vijayakumar

doi:10.1107/S1600536809033364

. 2009 Aug 26;65(Pt 9):o2255–o2256. doi: 10.1107/S1600536809033364

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

Hoong-Kun Fun ^a,^*,^‡, Ching Kheng Quah ^a,^§, B Palakshi Reddy ^b, S Sarveswari ^b, V Vijayakumar ^b

PMCID: PMC2969859 PMID: 21577652

Abstract

In the title molecule, C₁₉H₂₃NO₅, the dihedral angle formed by the benzene ring and the planar part of the dihydropyridine ring is 83.52 (5)°. The dihydropyridine ring adopts a flattened boat conformation. In the crystal, molecules are linked by N—H⋯O hydrogen bonds, generating chains running parallel to [100]. The crystal structure is consolidated by C—H⋯O contacts.

Related literature

For general background to Hantzsch 1,4-dihydropyridines (1,4-DHPS), see: Gaudio et al. (1994 ▶); Bocker & Guengerich (1986 ▶); Gordeev et al. (1996 ▶); Sunkel et al. (1992 ▶); Vo et al. (1995 ▶); Cooper et al. (1992 ▶). For a related structure, see: Fun et al. (2009 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). For geometric analysis, see: Cremer & Pople (1975 ▶). For the stability of the temperature controller used for the data collection, see: Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C₁₉H₂₃NO₅
M _r = 345.38
Triclinic,
a = 7.4108 (1) Å
b = 9.7459 (2) Å
c = 12.3359 (2) Å
α = 87.412 (1)°
β = 86.244 (1)°
γ = 76.402 (1)°
V = 863.72 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 100 K
0.39 × 0.33 × 0.19 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2005 ▶) T _min = 0.963, T _max = 0.982
26880 measured reflections
4579 independent reflections
3972 reflections with I > 2σ(I)
R _int = 0.026

Refinement

R[F ² > 2σ(F ²)] = 0.036
wR(F ²) = 0.099
S = 1.05
4579 reflections
235 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.38 e Å⁻³
Δρ_min = −0.23 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/S1600536809033364/tk2529sup1.cif

e-65-o2255-sup1.cif^{(21.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809033364/tk2529Isup2.hkl

e-65-o2255-Isup2.hkl^{(224.3KB, 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⋯O4ⁱ	0.854 (15)	2.230 (15)	3.0710 (11)	168.0 (13)
C4—H4A⋯O1ⁱⁱ	0.93	2.58	3.5104 (12)	174
C15—H15A⋯O1ⁱⁱⁱ	0.96	2.60	3.5500 (14)	172
C19—H19B⋯O4ⁱ	0.96	2.57	3.4677 (12)	155

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

HKF and CKQ thank Universiti Sains Malaysia (USM) for a Research University Golden Goose Grant (No. 1001/PFIZIK/811012). CKQ thanks USM for a Research 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 include various vasodilator, anti-hypertensive, bronchodilator, hepatoprotective, 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 (Bocker & Guengerich, 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 DHPs have been introduced as neuroprotectants and cognition enhancers. In addition, a number of DHPs with platelet anti-aggregatory activity have also been discovered (Cooper et al., 1992).

The geometric parameters in (I), Fig. 1, are comparable to those in a closely related structure (Fun et al., 2009). The benzene ring (C1—C6) and dihydropyridine ring (C7—C11/N1) are nearly perpendicular as seen in the angle of 83.52 (5)° between their least-squares planes. The dihydropyridine ring adopts a flattened boat conformation with puckering parameters (Cremer & Pople, 1975) Q = 0.2688 (10) Å; Θ = 73.7 (2)° and φ = 183.6 (2)°, with atoms N1 and C7 deviating by 0.125 (1) and 0.172 (1) Å, respectively, from the mean plane of the dihydropyridine ring.

In the solid-state (Fig. 2), the molecules are linked via N1—H1N1···O4 hydrogen bonds (Table 1) to generate supramolecular chains running parallel to the [1 0 0] direction. The O4 atom also participates in a C19—H19B···O4 contact to generate, along with the N1—H1N1···O4 hydrogen bond, a R₂¹(6) ring motif (Bernstein et al., 1995); Fig. 2. Molecules are further consolidated by intermolecular C—H···O interactions (Table 1).

Experimental

Compound (I) was prepared according to the Hantzsch pyridine synthesis. A mixture of 4-ethoxybenzaldehyde (10 mmol), methylacetoacetate (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 was extracted using diethyl ether and the mother liquors kept for crystallization. The purity of the crude product was checked through TLC and recrystallized using acetone and ether; M.p. 403–405 K. IR (KBr): υ: 3361, 2985, 2948, 1682, 1652, 1485, 1235 cm^-1.