Purines. XXIX. Syntheses of 9-Alkyl-2-deuterio-N6-methoxyadenines and 2-Deuterio-N6, 9-dimethyladenine

Cyclizations of the alkoxyamidines 7a, i with formic acid gave N6-methoxy-9-methyladenine (8a) and 9-benzyl-N6-methoxyadenine (8i). Replacement of formic acid by formic-d acid-d in these cyclizations afforded the 2-deuterated species 13a and 13i. A similar cyclization of 22, obtained from 21 by alkaline hydrolysis, with formic-d acid-d yielded 2-deuterio-N6-methoxy-1, 9-dimethyladenine (24). The N6-methyl isomer 19 was prepared from 13a by treatment with NaH and MeI. Comparison of the proton nuclear magnetic resonance (1H-NMR) spectrum of 8a in Me2SO-d6 with that of 13a revealed that 8a exists as an equilibrated 1 : 3.5 mixture of the amino (type 14 or 15) and the imino (type 16 or 17) forms. The deuterated species 19 and 24 were utilized for interpretation of the 1H-NMR spectra of the amino-form model 18 and the imino-form model 23. The existence of amino-imino tautomerism in 8a was also supported by ultraviolet and infrared spectroscopic evidence. Such tautomerism, with a preference for the imino form, in Me2SO-d6 was found to be common to 13 other 9-substituted N6-alkoxyadenines (type 8) including adenosine analogues. On the other hand, comparison of the 1H-NMR spectra of 11, N6, 9-dimethyladenine (12), and N6, N6, 9-trimethyladenine (36) indicated that 12 exists solely in the amino form in CDCl3 or Me2SO-d6.