Purines. XVIII. Kinetic Studies of the Dimroth Rearrangement of 1-Alkoxy-9-methyladenines and 1-Benzyloxyadenosine : Effect of 1-Benzyloxy and 9-β-D-Ribofuranosyl Groups on the Rates of the Ring-opening and the Reclosure

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Rates of the Dimroth rearrangements of 1-benzyloxyadenosine (Id) and 1-alkoxy-9-methyladenines (Ia-c), which give the rearranged products (IIIa-d) and the deformylated compounds (IVa-d) competitively through the isolable monocyclic intermediates (IIa-d), have been measured at different pH's and ionic strength 1.0 at 40°. It has been shown that all reactions obey good pseudo-first-order kinetics. The ring-opening (I→II) follows the rate law given by k⁽⁰⁾_{II. obsd}[I]_total=k⁽⁰⁾_{II. lonie}[I·H⁺][OH^-]+k⁽⁰⁾_{II. neit}[I][OH^-] where k⁽⁰⁾_{II. obsd} is the observed limiting rate constant for zero buffer concentration ; [I·H⁺] is the concentration of the protonated base ; [I], the concentration of the free base ; [I]_total, the sum of [I·H⁺] and [I]. Comparison of the individual second-order rate constants thus obtained (Table III) has revealed that attack of hydroxide ion on the protonated species is faster than on the neutral species by a factor of 560-1200 and that both reaction modes are promoted by the β-D-ribofuranosyl substituent at the 9-position. Both the ring-closure (II→III) and the deformylation (II→IV) in 0.1M buffer solutions are enhanced by the β-D-ribofuranosyl group at the 1-position of II, whereas the benzyl group on the O-atom of the amidoxime moiety of II exerts the stabilizing effect on II. The unusually low pK_a's of 9.9 to 10.6 at 40°observed for II have been assigned to the acidic ones of the formamido group of II. Probable mechanisms for the ring-closure and the deformylation of II are also described.