Firstly, in a test reaction, we used a series of bases with decreasing strength as lithiation reagent: tert-BuLi (pKa = 53), sec-BuLi (pKa = 51), n-BuLi (pKa = 50), MeLi (pKa = 48) and PhLi (pKa = 43). The weakest base phenyl lithium (PhLi) gave the best results with respect to the yield of dilithiated product, which was quenched with trimethylsilylchloride (50%), and to the lowest portion of decomposition of the substrate (4%). In contrast, with the strongest base tert-BuLi no product was obtai-ned and 100% of the starting material were decomposed. The other bases gave intermediate results. Further optimization of the lithiation reaction of dithienopyrazine 6 with PhLi as base in THF at -95°C and tetrabromomethane as quenching reagent gave 2,6-dibromo derivative 18 in 83% yield. Similarly, lithiation of 6 with PhLi in THF at -78°C and quenching with elemental iodine was likewise effective and corresponding 2,6-diododerivative 19 was obtained as well in 83% yield. In both cases, small amounts of mono-substituted product were easily removed by column chromatography. Besides the lithiation/halogenation sequence, transmetallation of the intermediate diltihiated dithienopyrazine 6 was undertaken with tributylstannylchloride and bis-stannylated syn-dithienopyrazine 20 was isolated in 79% yield. Analogous lithiation of isomeric dithienopyrazine 5 with PhLi as base in THF at -95°C and tetrabromomethane as quenching reagent gave the 2,6-dibromo derivative 21. Due to the lower solubilty of the anti-derivative 5 in THF compared to 6 a substantially higher dilution was necessary. This obviously led to a lower yield of 38% of dibrominated 21 whereby in this case a monobrominated derivative was isolated as a side product in 26% yield. These investigations showed that by electrophilic halogenation and the lithiation/halogenation sequence different substitution patterns at the dithienopyrazines 5 and 6 were achieved: direct halogenation leads to -substitution, the latter procedure to -substituted derivatives. Structural proofs were made by NMR and single crystal X-ray structure analysis and are discussed below.