Purines. XIV. Synthesis and properties of 8‐nitroxanthine and its N‐methyl derivatives

Xanthine (1) and its N‐methyl derivatives 2–16 have been nitrated to the corresponding 8‐nitro derivatives 17–32 under different reaction conditions. Nitration in glacial acetic acid with nitric acid works well with the N‐7 unsubstituted and some of the 9‐methylxanthines, respectively, whereas the 7‐methylxanthine derivatives react best with nitronium tetrafluoroborate in sulfolane or glacial acetic acid. The 8‐nitro group can be displaced nucleophilically to form 8‐chloro‐, 33, 34, 8‐ethoxy‐, 35,36, and uric acid derivatives 37–40, respectively. The newly synthesized 8‐nitroxanthines have been characterized by elemental analyses, pK‐determinations and uv and 1H‐nmr spectra.