Diethyl 4-(4,5-dihydro­furan-2-yl)-3,5-di­methyl-1-phenyl-1,4-dihydro­pyrazine-2,6-dicarboxyl­ate

Jing-Yu He; Zhi-Lin Tan; Hong Yan

doi:10.1107/S1600536809013749

. 2009 Apr 25;65(Pt 5):o1129. doi: 10.1107/S1600536809013749

Diethyl 4-(4,5-dihydrofuran-2-yl)-3,5-dimethyl-1-phenyl-1,4-dihydropyrazine-2,6-dicarboxylate

Jing-Yu He ^a, Zhi-Lin Tan ^a, Hong Yan ^a,^*

PMCID: PMC2977802 PMID: 21583939

Abstract

In the title compound, C₂₂H₂₆N₂O₅, the central 1,4-dihydropyrazine ring adopts a boat conformation, while the benzene ring and the two disordered components of the furan ring are inclined at angles of 77.9 (5) and 61.9 (7)°. Three of the C atoms of the furan ring are disordered over two positions with occupancies of 0.655 (18) and 0.345 (18). In the crystal structure, weak intermolecular C—H⋯O hydrogen bonds link the molecules into chains propagating in [010].

Related literature

For the biological properties of 1,4-dihydropyrazines, see: Goto et al. (1968 ▶); Teranishi & Goto (1990 ▶). For their biomedical applications, see: Brook et al. (1992 ▶); Sit et al. (2002 ▶). For the synthesis of 1,4-dihydropyrazines, see: Wolfbeis (1977 ▶); Chorvat & Rorig (1988 ▶); Rodrigues et al. (2004 ▶).

Experimental

Crystal data

C₂₂H₂₆N₂O₅
M _r = 398.45
Triclinic,
a = 10.069 (2) Å
b = 10.242 (2) Å
c = 12.519 (3) Å
α = 72.37 (3)°
β = 77.59 (3)°
γ = 63.76 (3)°
V = 1098.8 (4) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 293 K
0.50 × 0.40 × 0.25 mm

Data collection

Rigaku R-AXIS RAPID IP diffractometer
Absorption correction: multi-scan (ABSCOR; Higashi, 1995 ▶) T _min = 0.958, T _max = 0.979
7345 measured reflections
3768 independent reflections
1555 reflections with I > 2σ(I)
R _int = 0.045

Refinement

R[F ² > 2σ(F ²)] = 0.059
wR(F ²) = 0.182
S = 0.84
3768 reflections
291 parameters
52 restraints
H-atom parameters constrained
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.13 e Å⁻³

Data collection: RAPID-AUTO (Rigaku, 2000 ▶); cell refinement: RAPID-AUTO; data reduction: CrystalStructure (Rigaku/MSC, 2000 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809013749/hb2937sup1.cif

e-65-o1129-sup1.cif^{(25.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809013749/hb2937Isup2.hkl

e-65-o1129-Isup2.hkl^{(184.7KB, 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
C12—H12C⋯O5ⁱ	0.96	2.67	3.618 (5)	169

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank Professor Jim Simpson of the University of Otago for extensive assistance in refining the single-crystal data and editing the manuscript. This work was supported by the National Natural Sciences Foundation (grant No. 20872009), the Natural Sciences Foundation of Beijing (grant No. 200710005002), and Key Projects in the National Science and Technology Pillar Program during the Eleventh Five-Year Plan Period (grant No. 2008ZX10001-015).

supplementary crystallographic information

Comment

The application of 1,4-dihydropyrazines in the field of biological agents and medicines has been widely investigated (Brook, et al., 1992, Sit, et al., 2002.), because 1,4-dihydropyrazine unit was found to be a component of the flavin coenzymes and several marine luciferins (Goto et al., 1968; Teranishi & Goto, 1990). Although the synthesis of 1,4-dihydropyrazines has been studied for many years (Wolfbeis 1977; Chorvat & Rorig 1988; Rodrigues et al. 2004), their photochemical properties have not been paid much attention in the literature to date.

The photochemical stability of 2,6-diethoxycarbonyl-3,5-dimethyl-1-phenyl-1,4-dihydro- pyrazine (II) was investigated in a variety of conventional solvents such as benzene, THF, acetone, ethyl acetate, ethyl nitrile, n-hexane, ether, methanol and dichloromethane. In THF, the title compound (I), was obtained in a yield of ca 5% after irradiation for 8 h with a high-pressure Hg lamp. A similar transformation also occurred by irradiation with sunlight, ultraviolet, or other lower powered light sources. The present X-ray crystal structure analysis was undertaken, to study the stereochemistry and crystal packing of (I).

In (I) (Fig. 1), the 1,4-dihydropyrazine ring (N1/C3/C2/N2/C6/C7) adopts a boat conformation: atoms C2, C3, C6 and C7 are coplanar, with atoms N1 and N2 deviating from this plane by 0.517 (4) and 0.362 (5) Å, respectively. The dihedral angle between the phenyl ring and C2/C3/C6/C7 plane is 70.46 (18)°. with those between the phenyl ring and the two disorder components of the furan ring are 77.9 (5)° and 61.9 (7)° respectively. In the crystal structure, weak intermolecular C—H···O hydrogen bonds (Table 1) link the molecules into chains propagated along b axis.

Experimental

Diethyl 3,5-dimethyl-1-phenyl-1,4-dihydropyrazine-2,6-dicarboxylate, (330 mg, 1 mmol) was dissolved in dry furan (30 ml) and poured into the photolysis unit. The solution was irradiated with a 500 W Hg lamp. The reaction was monitored by TLC. After 8 h, the solvent was removed in vacuo and the crude sample was purified on a silica-gel column using an n-hexane/ethyl acetate (20:1 v/v) as eluant. Colourless blocks of (I) were obtained by slow evaporation of a n-hexane / ethyl acetate solution (3:1 v/v) in a yield of 5.2% (21 mg; m.p. 421–423 K).