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

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.


Experimental
Crystal data [Pd(C 12  thesis 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(PPh 3 ) 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 PPh 3 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 PPh 3 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(PPh 3 ) 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.

Refinement
Hydrogen atoms were positioned geometrically; U iso (H) = xU eq (C), where x = 1.5 for methyl and 1.2 for all other H atoms.
The asymmetric unit contains a solvent accessible void (164.3 Å 3 ). The contribution of the disordered solvent atoms were taken into acount by the squeeze algorithm implemented in the PLATON program (Spek, 2003) for a total of 52.4 electrons. Fig. 1. The molecular structure of the title compound (I), showing the atom-labeling scheme with displacement ellipsoids drawn at the 50% probability level. H atoms have been omitted for clarity.

trans-Chlorido[6-chloro-4-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazin-2yl]bis(triphenylphosphine)palladium(II)
Crystal data [Pd(C 12   Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2sigma(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.