Diisopropyl 1-(4-meth­oxy­phen­yl)-2,6-dimethyl-4-(3-nitro­phen­yl)-1,4-dihydro­pyridine-3,5-dicarboxyl­ate

Kamini Kapoor; Vivek K Gupta; Rajni Kant; Milind P Pawar; Hitendra S Joshi

doi:10.1107/S1600536811042073

. 2011 Oct 22;67(Pt 11):o2979. doi: 10.1107/S1600536811042073

Diisopropyl 1-(4-methoxyphenyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Kamini Kapoor ^a, Vivek K Gupta ^a, Rajni Kant ^a,^*, Milind P Pawar ^b, Hitendra S Joshi ^b

PMCID: PMC3247382 PMID: 22220000

Abstract

In the title compound, C₂₈H₃₂N₂O₇, the 1,4-dihydropyridine ring adopts a flattened boat conformation. The two benzene rings are approximately perpendicular to the dihydropyridine ring, forming dihedral angles of 84.29 (9) and 82.96 (9)° with the mean plane of the 1,4-dihydropyridine unit, whereas the ester groups are only slightly twisted relative to this plane, with dihedral angles of 10.6 (1) and 9.0 (1)°.

Related literature

For background to the pharmaceutical applications of 1,4-dihydropyridine derivatives, see: Gaveriya et al. (2001 ▶); Shah et al. (2000 ▶, 2002 ▶); Marchalin et al. (2004 ▶); Chhillar et al. (2006 ▶).

Experimental

Crystal data

C₂₈H₃₂N₂O₇
M _r = 508.56
Triclinic,
a = 9.5043 (8) Å
b = 10.7570 (7) Å
c = 15.1279 (12) Å
α = 90.501 (6)°
β = 105.873 (7)°
γ = 114.601 (7)°
V = 1339.27 (18) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 293 K
0.30 × 0.20 × 0.20 mm

Data collection

Oxford Diffraction Xcalibur S diffractometer
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2007 ▶) T _min = 0.825, T _max = 1.000
8313 measured reflections
4688 independent reflections
2417 reflections with I > 2σ(I)
R _int = 0.043

Refinement

R[F ² > 2σ(F ²)] = 0.069
wR(F ²) = 0.203
S = 0.93
4688 reflections
334 parameters
H-atom parameters constrained
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.23 e Å⁻³

Data collection: CrysAlis CCD (Oxford Diffraction, 2007 ▶); cell refinement: CrysAlis CCD; data reduction: CrysAlis RED (Oxford Diffraction, 2007 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶) and PARST (Nardelli, 1995 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811042073/gk2409sup1.cif

e-67-o2979-sup1.cif^{(25KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811042073/gk2409Isup2.hkl

e-67-o2979-Isup2.hkl^{(225KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811042073/gk2409Isup3.cml

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

Acknowledgments

RK acknowledges the Department of Science & Technology for the single-crystal X-ray diffractometer sanctioned as a National Facility under Project No. SR/S2/CMP-47/2003.

supplementary crystallographic information

Comment

Studies on 1,4-dihydropyridine (1,4-DHP) derivatives have been carried out in many research institutes all over the world because of their attractive biological activities ( Marchalin et al., 2004; Chhillar et al., 2006). 1,4-Dihydropyridines have played important role as chemotherapeutic agents, such as multi-drug resistance reversal in tumor cells (Shah et al., 2000), potential immunomodulating (Shah et al., 2002) and antitubercular compounds (Gaveriya et al., 2001; Shah et al., 2002). These compounds have also been investigated for other pharmacological activities such as antidiabetic, antiviral, antibacterial, membrane protecting, anticancer and antimicrobial. Calcium channel blockers of the 1,4-dihydropyridine derivatives, exemplified by nifedipine and nilvadipine, are well known as clinically important drugs since they first appeared on the market in 1975. To date, the structure-activity relationship of the DHPs has indicated that the desired structural characteristic of the substituents at the 4-position of the dihydropyridine nucleus had been thought to be the benzene ring. A favorable substituent on the 4-phenyl ring of DHP derivatives was suggested to be an electron-withdrawing group, such as the nitro group. Nitrophenyl substitution led to many cardiovascular drugs, namely, nilvadipine, nimodipine, nicardipine, nisoldipine, nifrendipine, etc. In view of the above, the crystal structure of the title compound was determined.

The classical preparation method of 1,4-DHP is the Hantzsch method. However, the classical methods were not enough to make pyridine libraries. Development of an efficient and versatile method for the preparation of 1,4 - dihydropyridines is an active ongoing research area and we have synthesized the title compound using catalytic method. In catalytic method the overall yields of the product are higher than the conventional classical method.

As in other dihydropyridine (DHP) structures, the DHP ring exhibits a flatened boat conformation. The N1 and C4 atoms lie 0.138 (3) and 0.336 (3) Å, respectively, from the least-squares plane defined by the remaining four atoms of the DHP ring. The puckering of the 1,4-DHP ring at N1 and C4, which is important for the biological activity of this class of compounds, is reflected in the torsion angles C3—C4—C5—C6 and C2—C3—C4—C5 which are 27.3 (4) and -26.5 (4)°o, respectively. The torsion angles about the bonds to N1 are -13.1 (5) (C2—N1—C6—C5) and 13.7 (5)° (C6—N1—C2—C3); All these values indicate that the puckering of the 1,4-DHP ring is largere at C4 site.

The values of the torsion angles, C6—N1—C9—C10 [-79.6 (4)°] and C5—C4—C29—C34 [79.9 (4)°]], describe the conformation around the inter-ring bond. The bezene rings are approximately perpendicular to the dihydropyridine ring. The dihedral angle found between the plane 1 (N1, C2, C3, C4, C5, C6) and plane 2 (C29, C30, C31, C32, C33, C34) is 84.29 (9)° and between the plane 1 (N1, C2, C3, C4, C5, C6) and plane 3 (C9, C10, C11, C12, C13, C14) is 82.96 (9)°. Owing to the absence of any strong donor group, cohesion of the crystal is mainly achieved by van der Waals interactions (Fig. 2)

Experimental

A mixture of 3-nitrobenzaldehyde (5 mmol, 0.45 g), isopropyl acetoacetate (10 mmol, 1.44 g), 4-methoxyaniline (5 mmol, 0.615 g) was heated (without solvent) on steam bath for 2.5h. After elimination of water, iodine (1.5 mmol, 0.38 g) and ethanol (5 ml) were added to the reaction mixture.The reaction mixture was stirred, at room temperature, till the reaction was complet(4h monitored by TLC). The reaction mixture was treated with aqueous Na₂S₂O₃ solution and the product was extracted with ethyl acetate (2x 20 ml). The solvent was removed under pressure and the resulting crude product (94%) was recrystallized from ethanol to give the analytical grade pure product. In catalytic method the overall yields of the product are higher than in the conventional classical method.