Purines. XV. Conversion of N,9-dimethyladenine into the 1,9-dimethyl isomer: A reverse operation of the Dimroth rearrangement.

Abstract

Oxidation of N, 9-dimethyladenine (IIIa) with m-chloroperbenzoic acid in ethanol or 30% aqueous hydrogen peroxide in acetic acid produced the 1-N-oxide (VIII). N-Oxide VIII underwent methylation at the oxygen atom when treated with methyl iodide in N, N-dimethylacetamide, giving 1-methoxy-N, 9-dimethyladenine hydriodide (IX·HI) in 89% yield. The Dimroth rearrangement of IX to N-methoxy-1, 9-dimethyladenine (XI) was readily effected by treating the free base (IX) with boiling water under mildly alkaline conditions. On the other hand, treatment of IX with water at room temperature furnished the ring-opened intermediate (X), which recyclized in boiling water to XI with the formation of a trace of the reversion product (IX). On treatment with 0.2N hydrochloric acid at room temperature, intermediate X gave both XI (62% yield) and IX (13% yield as the perchlorate). Catalytic hydrogenolysis of XI to 1, 9-dimethyladenine (Ia) (71% yield as the perchlorate), effected with hydrogen and Raney nickel catalyst, completed the reaction sequence which made possible a reverse Dimroth rearrangement of IIIa to Ia.