Purines. LXXV. Dimroth Rearrangement, Hydrolytic Deamination, and Pyrimidine-Ring Breakdown of 7-Alkylated 1-Alkoxyadenines: N(1)-C(2) versus N(1)-C(6) Bond Fission

On treatment with boiling H2O for 5-6h, 1-alkoxy-7-alkyladenines (13) underwent hydrolytic cleavage at the N(1)-C(2) and the N(1)-C(6) bonds to produce the imidazole-5-carboxamidines (14) in 53-60% yields and the imidazole-5-carboxamides (18) in 5-7% yields, respectively. The Dimroth rearrangement of 13 to N6-alkoxy-7-alkyladenine (15) was found to proceed through 14 more slowly than that of the 9-alkyl analogues 1 at pH 7 and above, being accompanied by hydrolysis to give the deformylated product (16) and by deamination through 18 leading to 7-alkylhypoxanthine (12), 1-alkoxy-7-alkylhypoxanthine (19), and 1-alkyl-4-aminoimidazole-5-carboxamide (20). Interestingly, the N(1)-C(6) bond fission product 17a was obtained from 13a by treatment with 0.01N aqueous NaOH at 4°C for 35d, but in only 2% yield, or more efficiently (in 56% yield) by pyrolysis at 150°C for 1h. On the other hand, 13 underwent acid hydrolysis faster than 1, providing the deformylated product 16 in 85-96% yields on treatment with 1-2N aqueous HCl at room temperature for 2-5h. 4-amino-N'-methoxy-1-methyl-5-carboxamidine (16a) was alternatively obtained in 59% yield by treatment of 1-methoxy-7-methyladenine (13a) with boiling 2N aqueous NaOH for 10min. Efficient preparations of the rearranged products 15 (80-86%) were accomplished by treating 13 with boiling 0.1N aqueous NaOH for 20-30min.