o-Quinonoid Heterocycles: Synthesis and Crystal Structure of 2,3-Dicyano-5,7-bismethylthieno[3,4-b]pyrazine

2,3-Dicyano-5,7-bismethylthieno[3,4-b]pyrazine (5), has been obtained as a minor product from reactions of S-nucleophiles with 5,6-di(1-bromoethyl)pyrazine-2,3-dicarbonitrile (3), or from a condensation of 4-hydroxy-2,5-dimethyl-2,3-dihydrothiophen-3-one (4) with diaminomaleonitrile. The molecular structure of compound 5 has been confirmed by X-ray diffraction. A partial separation of charge causes a donor-acceptor type arrangement of the planar molecules in uniform parallel stacks with an interplanar spacing of 3.334(2) A at 100 K.


Introduction
Several years ago we reported studies on 5,6-bis(bromomethyl)pyrazine-2,3-dicarbonitrile as a potential synthon for substituted azaphthalocyanines (AzaPcs) [1].Due to its extremely labile "benzylic" hydrogens, the dicarbonitrile was found to be too reactive towards base to be of general use.The branched 1-bromoethyl group, expected to be less reactive towards base, might be a good substitute for the bromomethyl group, but pyrazines with chiral side chains would result from reactions with nucleophiles.
The objective of the present work was to prepare and explore 5,6-bis(1-bromoethyl)pyrazine-2,3dicarbonitrile (3) as a synthon for octa-substituted AzaPcs.Reactions of 3 with sodium sulfide followed by oxidation, were expected to give 5 via the corresponding dihydrothiophene derivative.
Trisodium thiophosphate dodecahydrate, a reagent used for base sensitive substrates [4], gave an unexpected reaction with compound 3.A small amount (8 %) of a crimson red powder was obtained, identified as 2,3-dicyano-5,7-bismethylthieno [3,4-b]pyrazine (5).We were not able to isolate any of the expected dihydroanalogues of 5 from the tarry reaction mixture.A reaction where a solution of 3 in ethanol was added slowly to an ethanol solution of 60 % powdered sodium sulphide yielded 15 % of compound 5.In another experiment where the two reactants were mixed at once a slightly lower yield (11 %) of 5 was obtained.Other reaction products were polar compounds which could not be properly characterized due to slow decomposition.We were not able to convert any of these products to 5. Reactions of 3 with sodium sulfide in other solvents, i.e. 1-propanol, 1-butanol or quinoline gave lower yields of 5.
An alternative method for preparation of 5, or its dihydro analogue, would be a reaction of 4hydroxy-2,5-dimethyl-2,3-dihydrothiophen-3-one (4) with 1. Compound 4, a flavour enhancing substance for baked breads, has been reported in patents [5,6].However, although we found that phase transfer conditions were superior to the reported method of preparation, 4 was not in any instance obtained as a crystalline compound, as reported [6].A reaction of compound 4 with 1 gave compound 5 in low yield (3 %).

Crystal structure of compound 5
Compound 5 crystallized in space group P2 1 /m.With b as the unique axis this space group has mirror planes at y = ¼ and ¾.The asymmetric (unique) unit of 5 is one half molecule related to the other half through the crystallographic mirror planes.Figure 1 displays the mirror symmetry of the molecule, and confirms the assignment of its conformation from spectroscopy.All the non-hydrogen atoms are nearly confined to one plane, the thiophene and pyrazine rings are significantly coplanar.There is a small out-of-plane bending of the nitrile goups, the deviations of C(4) and N(2) from the common ring plane are 0.012(2) and 0.036(2) Å, respectively, the methyl C(5) atom is displaced by 0.021(2) Å to the opposite side of this plane.The structure of 5 thus conforms very closely to two orthogonal mirror planes, of which one is exact, the line of intersection runs through the midpoint of the C(3) -C(3') bond and the S atom.There is no strong anisotropy in the ADPs of the non-H atoms, hence, no indication of disorder at 100 K.The strong colour indicates an extended π electron delocalization.
Both the pyrazine ring and the two CN groups are electron attractive, causing a partial separation of charge, with excess positive charge on the S atom (or the thiophene ring) and excess negative charge on the pyrazine N atoms and the CN groups.The crystal structure of 5 is shown in Figure 2. The molecules form uniform stacks, all molecular planes are parallel and very nearly lying in the (1 0 1) planes.Molecules in neighbour stacks along b have their long axis turned in opposite directions.All molecules within a stack have the same orientation.The thiophene ring is directly facing the fragment containing ½ pyrazine ring and the cyano groups of the adjacent molecule of the same stack in a donor-acceptor like arrangement, promoted by the charge separation within the molecule.The interplanar distance is only 3.334(2) Å, which is comparable to the parent distance in the common hexagonal graphite, 3.354 Å (= c/2) at room temperature [14], or 3.341 Å at 100 K, calculated from the thermal expansion coefficient a(T) along c in [14].The short interplanar distance in 5 relays a significant electrostatic character of the intrastack interaction.The shortest lateral S

Method A with sodium sulfide
Finely ground 60 % sodium sulfide (0.10 g, 0.7 mmol) was dissolved in ethanol (20 mL).A solution of compound 3 (0.21 g, 0.6 mmol) in ethanol (20 mL) was added dropwise during 30 min, and the orange solution was stirred at ambient temperature for 48 h.The solvent was removed under reduced pressure, and the residue was extracted with benzene (2 x 10 mL).Removal of the benzene gave a glassy red residue (0.09 g) which was chromatographed on silica eluting with benzene.The fractions with R f (benzene) = 0.3 were combined to give 0.03 g of a red solid, which was recrystallized from benzene to yield 0.02 g (15 %) of compound 5, m.p. 263-265 °C (dec.).The rest of the benzene soluble material was eluted from the column with acetone and gave 0.06 g of a glassy solid, R f (CHCl 3 ) = 0, R f (benzene) = 0.This material decomposed slowly when kept in chloroform solution. 1H-NMR (CDCl 3 ) δ 1.3 -2.0 and 2.6 -2.9 (broad unresolved multiplets), 4.5 (weak, broad s).UV-vis (acetone) 329 nm.The benzene insoluble material was extracted with acetone and 0.05 g of a glassy brown solid was obtained from the acetone extract.This material was insoluble in water, but decomposed slowly in air.UV-vis (acetone): 330 nm.

Method B
A solution of 1 (1.08 g, 10 mmol) and 4 (1.44 g, 10 mmol) in acetonitrile (25 mL) was heated under reflux for 6 h, then heated at 45 0 C for 5 days.The solvent was removed under reduced pressure, and the residue chromatographed on silica with DCM.The first fractions yielded 0.06 g (3 %) m.p. 190 -300 0 C (dec); 1 H-and 13 C-NMR spectra were identical to those of 5 obtained by Method A. The silica column was emptied with acetone and compound 1, 0.5 g (46 %) m.p. 175 -184 °C (dec) was obtained from the oily residue with diethyl ether.

X-ray structure study of 5
Compound 5 produced by Method A with Na 2 S was obtained as an intergrowth of crimson red crystals by slow evaporation from a benzene solution.A small single crystal of size about 75 × 55 × 25 m m was cut from a larger specimen and used for the diffraction study.Intensity data were collected at 100 K on an Oxford Diffraction 6-circle diffractometer equipped with an Onyx CCD detector using synchrotron radiation.Frames of data were collected by 0.6 o scans in ω for a range of crystal orientations and detector 2θ settings so as to obtain a good coverage of reciprocal space out to a resolution of d = 0.75 Å (sinθ/λ = 0.667 Å -1 ).The data were corrected for Lorentz and polarization effects and merged.Structure solution was by direct methods as coded in the SHELX97 program package [15].In the subsequent full-matrix least-squares refinement based on F 2 the non-H atoms were treated with anisotropic atomic displacement parameters (ADPs), the H atoms with isotropic ADPs.No restraints on parameters were necessary.A survey of the data collection and structure refinement is given in Table 1.
Table 2 contains the crystal data.Supplementary crystallographic data has been deposited with the Cambridge Crystallographic Data Centre as CCDC 647482.These data can be obtained free of charge from CCDC via www.ccdc.cam.ac.uk/conts/retrieving.html.

Figure 1 .
Figure 1.Molecular conformation of compound 5.A few atoms generated by mirror symmetry have been labelled (primed numbers).ADP ellipsoids correspond to a 50 % probability.

Figure 2 .
Figure 2. Crystal structure showing the arrangement of planar molecules in stacks with alternating orientation along b.Within each stack there is strong intermolecular interaction.Colour code: S: orange, N: blue, C: grey, H: light grey.
and S••••N(2'), 3.366(2) Å, both N of the molcule at x-1, y, z+1, are normal van der Waals contacts connecting neighbour stacks along c.The cohesion in the b direction is much weaker.The shortest contacts in this direction are two of the type C─H••••N, at 2.77 and 2.71 Å, involving both N(1) and N(2) in two different molecules of the nearest stack along b.Contacts involving H have been calculated with the C─H bonds normalized to 1.10 Å.

Table 1 .
Summary of data collection and refinement.

Table 2 .
Crystal data for compound 5.