Purines: XLVII: 1) Dimroth Rearrangement versus Hydrolytic Deamination of 1-Ethyladenine

Abstract

The Dimroth rearrangement of 1-ethyladenine (6) to give 7V6-ethyladenine (11) (91% yield) was accompanied with unusual hydrolytic deaminations to produce hypoxanthine (8) (2%) and 1-ethylhypoxanthine (14) (2%), when carried out in 0.2 N aqueous NaOH at 100 °C for 7h. Probable pathways leading to these by-products are discussed on the basis of the results of alkaline hydrolysis of 5-amino-7V 'x2018;-ethyIimidazole-4-carboxamidine dihydrochloride (5), which yielded both 5-aminoimidazole-4-carboxamide (9) and 5-amino-N-ethylimidazole-4-carboxamide (12). For structural identification, 14 was alternatively synthesized from inosine (17) through 1-ethylinosine (16), and 12 was synthesized from 16 through 5-amino-N-ethyl-1-/I-D-ribofuranosylimidazole-4-carboxamide (15). Comparison of the reaction rates in the Dimroth rearrangements of 6-HC104 and l-ethyl-9-methyladenine perchlorate [1 -HC104 (R1 = Et; R2 = Me)] in H20 at pH 6.92 and 8.70 (ionic strength 1.0) at 70 °C has revealed that nonsubstitution at the 9-position decreases the rearrangement rate by a factor of 4-30 under these conditions. © 1990, The Pharmaceutical Society of Japan. All rights reserved.