Purines. LXXIII. Syntheses of 8-alkoxy- and 8-hydroxy-3-alkyladenines from 3-alkyladenine 7-oxides through 7-alkoxy-3-alkyladenines

Article abstract of DOI:10.1248/cpb.44.2025

7-Alkoxy-3-alkyladenine perchlorates (9) were prepared from 3- alkyladenines (4) by N-oxidation followed by alkylation with alkyl halides in N,N-dimethylacetamide. The 7-methoxy derivatives 9d,g,j thus obtained afforded 3-methyl-8-hydroxyadenine (7a), 3-ethyl-8-hydroxyadenine (7b), and 3-benzyl-8-hydroxyadenine (7c) in 74%, 72%, and 39% yields, respectively, on treatment with boiling 0.1 N aqueous sodium hydroxide, whereas treatment of 9d, g, j with sodium methoxide in methanol at room temperature afforded 3- alkyl-8-methoxyadenines (10m, p,q) in 91%-98% yields. Similar treatment of 9d with sodium ethoxide in ethanol afforded 8-ethoxy-3-methyladenine (10n) in 89% yield. Compounds 10m, q were alternatively prepared from 9d,j in 77% and 84% yields, respectively, by treatment with 0.1 N aqueous sodium hydroxide in the presence of methanol. This method was suitable for the synthesis of the 8-benzyloxy compound too: it was obtained in 60% yield by treating 7- benzyloxy-3-methyladenine perchlorate (9f) with a mixture of aqueous sodium hydroxide and benzyl alcohol. Compounds 7 were alternatively prepared from 9 through 10. For example, 7c was obtained in 84% overall yield by treatment of 9j with sodium methoxide, followed by hydrolysis of the resulting 10q with boiling 1 N hydrochloric acid. On the other hand, methylation of 3- methyladenine 7-oxide (8a) with dimethyl sulfate in 0.1 N aqueous sodium hydroxide in the absence or presence of added methanol afforded N⁶,3- dimethyladenine 7-oxide (14) in 13% or 14% yield, together with 7a (4% yield) or 10m (11%).

Full text of DOI:10.1248/cpb.44.2025

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