Purines: Part XVI : Syntheses, Properties, and Reactions of 8-Aminoxanthines

Abstract

A series of N‐substituted 8‐aminoxanthines (=8‐amino‐3,7(or 3,9)‐dihydro‐1H‐purine‐2,6‐diones) 8–16 and 34–37 were synthesized from the corresponding 8‐nitroxanthines 1–7, 30–33, and 8‐(phenylazo)xanthines 17 and 18 by catalytic reduction. Another approach was derived from 6‐amino‐5‐(cyanoamino)uracils (=N‐(6‐amino‐1,2,3,4‐tetrahydro‐2,4‐dioxopyrimidin‐5‐yl)cyanamides) 23, 24, and 27 by base‐catalyzed cyclization yielding 25–28. All 8‐aminoxanthines 8–29 and 34–37 were acetylated to the corresponding 8‐(acetylamino)xanthines 40–57, and prolonged heating led to 8‐(diacetylamino)xanthines 58 and 59. Several 8‐aminoxanthines 8–13 were diazotized forming 8‐diazoxanthines 60–64. Coupling reactions of isolated 62 and 64 and intermediary formed 8‐diazoxanthines with 1,3‐dimethylbarbituric acid (=1,3‐dimethylpyrimidine‐2,4,6(1H,3H,5H)‐trione; 66) resulted in 5‐[(xanthin‐8‐yl)diazenyl]‐1,3‐dimethylbarbituric acids=3,7(or 3,9)‐dihydro‐8‐[2‐(1,2,3,4‐tetrahydro‐1,3‐dimethyl‐2,4‐dioxopyrimidin‐5‐yl)diazenyl]‐1H‐purine‐2,6‐diones) 67–80. The newly synthesized xanthine derivatives were characterized by the determination of their pKa values, the UV‐ and NMR spectra, as well as elemental analyses.