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

Tara Shahani; Hoong-Kun Fun; B Palakshi Reddy; V Vijayakumar; S Sarveswari

doi:10.1107/S160053681001679X

. 2010 May 15;66(Pt 6):o1355–o1356. doi: 10.1107/S160053681001679X

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

Tara Shahani ^a, Hoong-Kun Fun ^a,^*,^‡, B Palakshi Reddy ^b, V Vijayakumar ^b, S Sarveswari ^b

PMCID: PMC2979474 PMID: 21579441

Abstract

In the title compound, C₁₉H₂₃NO₆, the 1,4-dihydropyridine ring is twisted slightly from planarity, with a maximum deviation of 0.101 (1) Å, and adopts a very flattened boat conformation. The dihedral angle formed between the plane through the four C atoms of the 1,4-dihydropyridine ring and the benzene ring is 84.67 (7)°. In the crystal structure, intermolecular N—H⋯O and C—H⋯O hydrogen bonds link the molecules into a three-dimensional network.

Related literature

For background to the biological activity of 1,4-dihydropyridines, 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 the synthesis of Hantzsch pyridines, see: Rathore et al. (2009 ▶). For a related structure, see: Shahani et al. (2009 ▶). For reference bond-length data, see: Allen et al. (1987 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶). For the stability of the temperature controller used for the data collection, see: Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C₁₉H₂₃NO₆
M _r = 361.38
Triclinic,
a = 7.3883 (6) Å
b = 10.0775 (8) Å
c = 12.3833 (10) Å
α = 105.372 (2)°
β = 90.255 (2)°
γ = 91.611 (2)°
V = 888.60 (12) Å³
Z = 2
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 100 K
0.51 × 0.41 × 0.18 mm

Data collection

Bruker APEXII DUO CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.950, T _max = 0.982
15520 measured reflections
4693 independent reflections
3996 reflections with I > 2σ(I)
R _int = 0.023

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.117
S = 1.05
4693 reflections
327 parameters
All H-atom parameters refined
Δρ_max = 0.39 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); 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/S160053681001679X/wn2383sup1.cif

e-66-o1355-sup1.cif^{(22.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053681001679X/wn2383Isup2.hkl

e-66-o1355-Isup2.hkl^{(229.9KB, 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⋯O5ⁱ	0.88 (2)	2.21 (2)	3.0750 (13)	166.7 (16)
C12—H12C⋯O4ⁱⁱ	0.926 (16)	2.550 (17)	3.4120 (17)	155.0 (13)
C15—H15C⋯O2ⁱⁱⁱ	0.968 (19)	2.501 (19)	3.4136 (17)	157.0 (17)
C17—H17C⋯O5ⁱ	0.98 (2)	2.52 (2)	3.4318 (14)	154.9 (15)
C19—H19A⋯O5^iv	0.954 (17)	2.562 (18)	3.5023 (15)	168.7 (13)

Open in a new tab

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

Acknowledgments

TSH and HKF thank Universiti Sains Malaysia (USM) for the Research University Golden Goose Grant (1001/PFIZIK/811012). VV is grateful to the 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, antihypertensive, bronchodilator, heptaprotective, antitumor, antimutagenic, geroprotective and antidiabetic agents (Gaudio et al., 1994) Nifedipine, nitrendipine, nimodipine etc. 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 neuroprotectant and cognition enhancers. In addition, a number of DHPs with platelet antiaggregatory activity have also been discovered (Cooper et al., 1992).

In the title compound (Fig. 1), the 1,4-dihydropyridine (C7–C9/N1/C10/C11) ring is slightly twisted from planarity, with a maximum deviation of 0.101 (1) Å at atom C11, and adopts a very flattened boat conformation (Cremer & Pople, 1975), with puckering parameters Q = 0.2412 (12) Å, Θ = 75.8 (3)° & φ = 183.4 (3)°. The dihedral angle formed between the plane through the four atoms C8-C11 of the 1,4-dihydropyridine and benzene (C1–C6) ring is 84.67 (7)°. The bond lengths (Allen et al., 1987) and angles are within normal ranges and comparable to those in a closely related crystal structure (Shahani et al., 2009).

In the crystal packing (Fig. 2), intermolecular N1—H1N1···O5, C12—H12C···O4, C15—H15C···O2, C17—H17C···O5 and C19—H19A···O5 hydrogen bonds (Table 1) link the molecules into a three-dimensional network.

Experimental

Dimethyl-1,4-dihydro-2,6-dimethyl-4-(3,4-dimethoxyphenyl)-3,5-pyridine dicarboxylate was prepared according to the Hantzsch pyridine synthesis (Rathore et al., 2009). A mixture of 3,4-dimethoxybenzaldehyde (10 mmol), methyl acetoacetate (20 mmol) and ammonium acetate (10 mmol) was heated at 80 °C for 2 hours (monitored by TLC). After completion of the reaction, the mixture was cooled to room temperature and allowed to stand for 1 day to obtain a solid product. This solid was washed with diethyl ether and the title compound obtained from the washings by evaporation. The purity of the crude product was checked by TLC and recrystallized using acetone and diethyl ether. Mp: 156-158 °C, IR (KBr):ν (cm^-1), 3361, 2994, 1701, 1654, 1217.