Purines. XXXII. : Synthesis and Ring Fission of 3,9-Dialkyladenines

A detailed account is given of the general synthetic route to 3,9-dialkyladenine salts (3d-I・HX) from N'-alkoxy-1-alkly-5-formamidoimidazole-4-carboxamidines (type 8 or 9), obtainable by ring opening of 1-alkoxy-9-alkyladenines (type 6 or 7). Alkylations of 8a and 9b, c with alkyl halides in HCONMe_2 in the presence of NaH or anhydrous K_2CO_3 produced N'-alkoxy-1-alkyl-5-(N-alkylformamido)imidazole-4-carboxamidines (10d-f and 1lg-l) in good yields. Hydrogenolyses of 10d-f and 11g-l using hydrogen and Raney Ni catalyst in the presence of one molar eq of HCl afforded 1-alkyl-5-(N-alkylformamido)imidazole-4-carboxamidines (12d-l・HCl). On treatment with HCl, HClO_4,or Et_3N in boiling MeOH or EtOH, the amidines 12d-l・HCl cyclized to give 3,9-dialkyladenines (3d-l), which were isolated as the HCl or HClO_4 salts. 9-Alkyl-3-methyladenine salts (3d, g, j・HX) were alternatively synthesized from 8a and from 9b, c through a 3-step route, which consisted of LiAlH_4 reduction of the formamido group, cyclizations of the resulting 5-(methylamino)imidazoles (15a and 16b, c) with CH(OEt)_3 to give N^6-alkoxy-9-alkyl-3-methyladenines (17a and 18b, c), and dealkoxylation of 17a and 18b, c by catalytic hydrogenolysis. 3,9-Dialkyladenine salts (3d-l・HX) thusprepared were found to be unstable in alkaline aqueous solution. In 0.1 M aqueous NaHCO_3,3d・HCl and 3f・HClO_4 were equilibrated with their ring-opened derivatives, 12d and 12f, respectively, and their equilibrium constants and rates of ring opening and cyclization at 25℃ were determined.