A General and Convenient Synthesis of 7-Alkyladenines from Adenine by Regioselective Alkylation Utilizing Blocking/Deblocking at the 3-Position

抄録

A detailed account is given of the final step of the general 7-alkalation procedure for adenine (1), which consists of the preferential benzylation at the 3-position of 1, regioselective alkylation of the resulting 3-benzyladenine (2) to give 7-alkyl-3-benzyladenine salts (3a-c), and debenzylation of 3a-c leading to 7-alkyladenines (4a-c). Debenzylation of 3a-c (X=Cl or ClO₄) has been achieved by hydrogenolysis using hydrogen and Pd-C catalyst at atmospheric pressure, producing 7-alkyladenines (4a-c) in 38-74% yields. The use of the allyl or γ, γ-dimethylallyl group at the 3-position instead of the benzyl group for the synthesis of 7-methyladenine (4a) by this procedure has no practical value. Alternatively, the salts 3a-c (X=Br, ClO₄, or I) have been debenzylated efficiently by treatment with conc. H₂SO₄ in the presence of toluene at room temperature for 3-6h or at 60°C for 0.5-2h, giving 4a-c in 73-93% yields.