Dimethyl 2,6-dimethyl-4-phenyl­pyridine-3,5-dicarboxyl­ate

Mukut Gohain; Theunis J Muller; Barend C B Bezuidenhoudt

doi:10.1107/S1600536811049865

. 2011 Nov 30;67(Pt 12):o3481. doi: 10.1107/S1600536811049865

Dimethyl 2,6-dimethyl-4-phenylpyridine-3,5-dicarboxylate

Mukut Gohain ^a, Theunis J Muller ^a,^*, Barend C B Bezuidenhoudt ^a

PMCID: PMC3239105 PMID: 22199953

Abstract

In the title compound, C₁₇H₁₇NO₄, the dihedral angle between the benzene and pyridine rings is 75.51 (4)°. The benzene and pyridine rings are both approximately planar (r.m.s. deviations of 0.0040 and 0.0083 Å, respectively), indicating that the pyridine N atom is not protonated. The crystal structure is stabilized by weak intermolecular C—H⋯O and C—H⋯N interactions.

Related literature

For the biological activity of pyridine derivatives, see: Lopez-Alarcon et al. (2004 ▶). For related structures, see: Rowan et al. (1996 ▶, 1997 ▶); Lou et al. (2010 ▶). For the sythesis, see: Debache et al. (2008 ▶). For the use of pyridine-type ligands in catalysis models, see: Roodt et al. (2011 ▶); van der Westhuizen et al. (2010 ▶) For standard bond lengths, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C₁₇H₁₇NO₄
M _r = 299.32
Monoclinic,
a = 16.0732 (4) Å
b = 7.2497 (2) Å
c = 13.1339 (3) Å
β = 91.003 (1)°
V = 1530.20 (7) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 100 K
0.42 × 0.36 × 0.18 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2004 ▶) T _min = 0.962, T _max = 0.984
26541 measured reflections
3782 independent reflections
3132 reflections with I > 2σ(I)
R _int = 0.036

Refinement

R[F ² > 2σ(F ²)] = 0.042
wR(F ²) = 0.114
S = 1.05
3782 reflections
203 parameters
H-atom parameters constrained
Δρ_max = 0.31 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT-Plus (Bruker, 2008 ▶); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg & Putz, 2005 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811049865/fk2046sup1.cif

e-67-o3481-sup1.cif^{(22.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811049865/fk2046Isup2.hkl

e-67-o3481-Isup2.hkl^{(181.7KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811049865/fk2046Isup3.cml

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
C6—H6B⋯O3ⁱ	0.98	2.42	3.3825 (15)	167
C7—H7B⋯O1ⁱⁱ	0.98	2.5	3.3826 (15)	149
C13—H13⋯N1ⁱⁱⁱ	0.95	2.62	3.2701 (16)	126
C15—H15A⋯O2^iv	0.98	2.56	3.5187 (17)	165

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

Acknowledgments

The University of the Free State and Sasol Ltd are gratefully acknowledged for financial support and Johannes van Tonder for the NMR data and help with the synthesis of the title compound. Special thanks are due to Prof Andreas Roodt.

supplementary crystallographic information

Comment

1,4-Dihydropyridines (1,4-DHPs) belong to a class of nitrogen containing heterocycles having a six-membered ring. These are analogues of NADH coenzymes and are an important class of drugs (Lopez-Alarcon et al. 2004). The oxidation of 1,4-DHP`s into the corresponding pyridines is one of the main metabolic pathways of these drugs. The title compound can be prepared by the catalytic oxidation of 1,4-dihydropyridine. The dihydropyrimidine synthesized by the known procedure through three components process disclosed in the literature (Debache et al. 2008). The oxidation of the dihdropyridine was carried out in the presence of 5 mol% of I₂ as a catalyst using DMSO as solvent. The title compound, C₁₇H₁₇N₁O₄, (Figure 1) crystallized in the monoclinic space group P2(1)/c with Z = 4. The dihedral angle between the benzene ring and the pyridine ring is 75.51 (4)°. This compares well to 75.3 (4)° from the structure reported by Lou et al. (2010). The benzene ring (C8—C13) is flat (r.m.s = 0.0040) as well as the pyridine (N1, C1—C4) ring (r.m.s =0.0083). So the nitrogen in the pyridine ring is not protonated (Rowan et al., 1996 and 1997). The methyl groups at C1 and C5 are above the plane at 0.0165 (20) Å and 0.0589 (19)Å respectively. The carboxylate groups at C2 and C4 are also out of the plane by 0.0521 (18) and -0.1049 (18) Å respectively. Bond lengths and angles are within expected ranges (Allen et al., 1987). The packing is further stabilized by weak intermolecular C6—H6B···O3ⁱ, C7—H7B···O1ⁱⁱ, C15—H15A···O2^iv and C13—H13···N1ⁱⁱⁱ interactions (Table 1). (i = -x + 1, -y, -z + 1; ii = -x, -y, -z + 1; iii = x, -y - 1/2, z + 1/2; iv = -x, y + 1/2, -z + 1.5)

Experimental

1,4-dihydropyridine synthesis: Methylacetoacetate (2.5 mmol) and benzaldehyde (1 mmol) was added to ethanol (10 ml) and stirred. To this 5 mol % of phenyl boric acid was added as catalyst. The mixture was heated to reflux and stirred until completion. After completion of the reaction (monitored by TLC) the precipitated was filtered off and dried in oven at 60 °C before it was dissolved in a KOH (2 mmol) containing DMSO solution(3 ml). Molecular iodine 5 mol% was added and the mixture stirred at room temperature until completion of the reaction(TLC). Ice cold water (20 ml) was subsequently added and the reaction mixture stirred for 30 min, before the product was extracted into ethyl acetate (3 x 20 ml) and the solvent removed under reduced pressure to yield the title compound as a white powder. Crystals suitable for x-ray analysis where obtained by slow evaporation of hexane and dicloromethane mixture (9:1; 2 ml) at 4 °C.

¹H NMR (600 MHz): 2.60 (s, 6H,2 x Methyl), 3.54 (s, 6H, 2 x methoxy), 7.24 (m, 2H, aromatic-H), 7.39 (m, 3H, aromatic-H).

¹³C NMR (150 MHz): 23.12, 52.35, 126.89, 126.87, 128.38, 128.68, 136.56, 146.41, 155.72, 168.59. m.p. 130–131 °C