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 ('H-NMR) spectrum of 8a in 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 'H-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 Me2S0-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 CDC13 or Me2S0-d6.
KeywordsN6-alkoxy-9-alkyladenine; N6-alkoxyadenosine; 9-alky1-2-deuterio-N6-methoxyadenine; 2-deuterio-N6,9-dimethyladenine; amino-imino tautomerism; 11-1-NMR; UV; IR An alkoxy group at the N6-position of adenine (1:R1 = H) and substituted adenines has been found of considerable synthetic utility because of its unique directivity in alkylation and substantial removability under hydrogenolytic conditions.2m The synthesis of 7,9-dialkyladeninium salts by us2a,c-e) from N6-alkoxy-9-alkyladenines (type 8) is a representative of such synthetic utility, culminating in the elegant syntheses of agelasine B, a sea sponge bicyclic diterpene with the 9-methyl-7-adeninylium moiety, and analogues by Tokoroyama's group.4) In 1966, we synthesized the N6-alkoxyadenines 8 for the first time and found that unambiguous assignments of the NH and the purine-ring proton signals in their nuclear magnetic resonance (NMR) spectra were difficult in many cases because of the complexity or dullness of the low-field signals. In order to interpret these spectra, we synthesized several 2-deuterated species and measured their 1 H-NMR spectra in the present study.The synthesis of the 2-deuterated species 13a and 13i was planned on the basis of our knowledge3) concerning fission and reclosure of the adenine ring, employing an alkoxy group at the 1-position, and of our recent success6) in synthesizing 9-substituted 2-deuterioadenines (type 5) from 9-substituted adenines (type 1) through the intermediates 2, 3, 4, 7, and 6 (Chart 1). Thus, the monocycle 7a5b) was treated with formic-d acid-d (of over 99% isotopic purity) in boiling MeCN for 6 h, giving 13a in 52% yield. The 1-benzyl analogue 7i6) was likewise cyclized to produce 13i in 63% yield. This...
