PURINES .14. 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 H-1-nmr spectra.