trans-Chlorido[6-chloro-4-(4-methoxy­benz­yl)-3-oxo-3,4-dihydro­pyrazin-2-yl]­bis­(triphenyl­phosphine)palladium(II)

Koen Robeyns; Jo Alen; Wim M De Borggraeve; Frans Compernolle; Luc Van Meervelt

doi:10.1107/S1600536807063441

. 2007 Dec 6;64(Pt 1):m93. doi: 10.1107/S1600536807063441

trans-Chlorido[6-chloro-4-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazin-2-yl]bis(triphenylphosphine)palladium(II)

Koen Robeyns ^a, Jo Alen ^b, Wim M De Borggraeve ^b, Frans Compernolle ^b, Luc Van Meervelt ^a,^*

PMCID: PMC2914967 PMID: 21200660

Abstract

The title compound, [Pd(C₁₂H₁₀ClN₂O₂)Cl(C₁₈H₁₅P)₂], is the intermediate of the reduction of a 3,5-dichloropyrazinone [Loosen, Tutonda, Khorasani, Compernolle & Hoornaert (1991 ▶). Tetrahedron, 47, 9259–9268]. This species is formed by oxidative addition of coordinatively unsaturated Pd⁰ to the reactive 3-position of the heterocycle. The coordination around the Pd atom is square planar, with two trans PPh₃ ligands. π–π interactions are observed between the centroid of the pyrazinone ring and planes of two adjacent phenyl rings, one from each PPh₃ group (3.25 and 3.078 Å), stabilizing the intermediate structure. This could explain the reduced reactivity towards substitution of the Cl atom by the formate anion, resulting in poor yield of the reduced compound. 3-Substituted pyrazinones are important precursors in the synthesis of 5-aminopiperidinone-2-carboxylate (APC) systems.

Related literature

For related literature on the reduction of 3,5-dichloropyrazinones, see: Loosen et al. (1991 ▶). For related literature on 3,5-dichloropyrazinones, see: Pawar & De Borggraeve (2006 ▶). For related literature on APC systems, see: De Borggraeve et al. (2004 ▶); Alen et al. (2007 ▶). For the Cambridge Structural Database (Version 5.28), see: Allen (2002 ▶). graphic file with name e-64-00m93-scheme1.jpg

Experimental

Crystal data

[Pd(C₁₂H₁₀ClN₂O₂)Cl(C₁₈H₁₅P)₂]
M _r = 916.06
Triclinic,
a = 10.7544 (1) Å
b = 13.1526 (1) Å
c = 16.9967 (1) Å
α = 91.811 (1)°
β = 94.39 (1)°
γ = 98.451 (1)°
V = 2368.83 (3) Å³
Z = 2
Cu Kα radiation
μ = 5.13 mm⁻¹
T = 100 (2) K
0.5 × 0.24 × 0.24 mm

Data collection

Bruker SMART 6000 diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1997 ▶) T _min = 0.175, T _max = 0.292
23121 measured reflections
8422 independent reflections
7879 reflections with I > 2σ(I)
R _int = 0.041

Refinement

R[F ² > 2σ(F ²)] = 0.029
wR(F ²) = 0.073
S = 1.08
8422 reflections
515 parameters
318 restraints
H-atom parameters constrained
Δρ_max = 0.58 e Å⁻³
Δρ_min = −0.58 e Å⁻³

Data collection: SMART (Bruker, 1997 ▶); cell refinement: SAINT (Bruker, 1997 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997 ▶); molecular graphics: ORTEPIII (Burnett & Johnson, 1996 ▶) and ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: PLATON (Spek, 2003 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536807063441/dn2294sup1.cif

e-64-00m93-sup1.cif^{(27.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536807063441/dn2294Isup2.hkl

e-64-00m93-Isup2.hkl^{(411.9KB, hkl)}

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

Acknowledgments

The Katholieke Universiteit Leuven is gratefully acknowledged for financial support. The authors thank the FWO [Fund for Scientific Research–Flanders (Belgium)] for financial support. JA and WMDB (Postdoctoral Fellows of the FWO–Flanders) thank the FWO for Fellowships received. WMDB also thanks the FWO for a ‘Krediet aan Navorsers’.

supplementary crystallographic information

Comment

The target structure 5-chloro-1-(4-methoxybenzyl)-2(1H)-pyrazinone) was synthesized as a starting product for the synthesis of dipeptide mimics (Alen et al., 2007; De Borggraeve et al., 2004). This compound can be formed by reduction of a 3,5-dichloropyrazinone with sodium formate using Pd(PPh₃)₄ as a catalyst. Surprisingly, the title compound (I) was isolated as an intermediate (Scheme 1, Fig. 1). This means that substitution of the chlorine atom with sodium formate and subsequent proton shift leading to the desired compound, did not occur. In similar reactions the yields are high and no traces of the intermediate substance are found. However, the presence of a hydrogen atom para to the palladium atom and a para-methoxybenzyl substituent on the N-1 nitrogen atom of the pyrazinone scaffold, seem to increase the stability of the intermediate. This stability might arise from the π–π interactions between the pyrazinone and two phenyl rings of the PPh₃ groups. The centroid of the pyrazinone makes a distance of 3.25 Å and 3.078 Å with the planes formed by the two adjacent phenyl rings. Searches in the CSD database (Version 5.28) (Allen, 2002) for similar structures (59 hits in 50 crystal structures) revealed that the angle between the pyrazinone ring and an adjacent phenyl ring is on average 27.6° (range 13.0° - 65.2°). As fragment for the CSD search a Pd atom with only four substituents (2 PPh₃ groups, any halogen and an aromatic ring consisting of any atom type) was used. In the represented structure the angles are 15.4° and 13.9°, resulting in almost parallel pyrazinone and adjacent phenyl rings.

Experimental

To a solution of 570 mg (2 mmol) 3,5-dichloropyrazinone in 20 ml DMF, 204 mg (3 mmol) sodium formate and 115 mg Pd(PPh₃)₄ are added. The solution is stirred for 4 h at 110 °C under inert atmosphere. After removal of the solvent, the residue is treated with 50 ml of water and extracted with 3x 50 ml dichloromethane. After drying over magnesium sulfate and evaporation of the solvent, the product was chromatographically purified (Heptane/EtOAc 50:50). The title compound was formed as a by-product with a yield of 45% and spontaneously crystallized from the Heptane/EtOAc mixture.