Abstract
In H2O at near neutrality, the 1-(ω-hydroxyalkyl)adenine derivatives 8a, b·HBr and 8c·HClO4 underwent hydrolytic deamination to give the 1-(ω-hydroxyalkyl)hypoxanthine derivatives 10a-c, in competition with the usual Dimroth rearrangement to produce the N6-(ω-hydroxyalkyl)adenine derivatives 9a-c. The rates of these competitive reactions were measured in H2O at various pH's and ionic strength 1.0 at 40°C, and the relative rate of deamination with respect to Dimroth rearrangement was found to increase as the pH of the reaction medium was decreased. Under similar conditions, the corresponding 1-alkyl analogues 8d-g·HClO4 and the 1-(modified benzyl) analogues 8h, i·HBr underwent only Dimroth rearrangement to afford the N6-isomers 9d-i. In the Dimroth rearrangements of all of the substrates 8a, b, d-i·HX (X=Br or ClO4), attack of hydroxide ion on the protonated species (8a, b, d-i·H+) at the 2-position was faster than that on the neutral species by a factor of 100-640. In the reaction of the protonated species, the 1-(ω-hydroxyalkyl) analogues 8a, b·HBr rearranged faster than the corresponding 1-alkyl analogues 8e, f·HClO4 by a factor of 1.6-2.7. It has been concluded that this rate enhancement is attributable solely to the electron-withdrawing effect, and not to intramolecular participation in catalysis, of the hydroxy group in the 1-substituent chain. In the syntheses of 8a, i·HBr from 9-ethyladenine (6) according to a general 1-alkylation procedure, the 7-alkylated products 13 and 16 were also obtained as by-products in 9% and 6% yields, respectively.
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