F. Tanaka

Purines—VI: Rate study and mechanism of the dimroth rearrangement of 1-alkoxy-9-alkyladenines and 1-alkyl-9-methyladenines☆

Abstract The rates of the Dimroth rearrangements of l-alkoxy-9-alkyladenines (I) and 1-alkyl-9-methyladenines (V) have been measured. It is shown that 1-alkoxy derivatives (I) undergo rearrangement to give isomeric 6-alkoxyamino derivatives (III) through isolable monocyclic intermediates (II) and that these intermediates also suffer hydrolysis leading to deformylated derivatives (IV) in competition with their reclosure to III. In the I-alkyl series, no intermediates have been detected and thus the observed first-order rate constants for the rearrangements may be regarded as those for the ring-opening of V. Comparison of the rate constants for 1-methoxy-9-methyladenine (Ia) and 1,9-dimethyladenine (Va) reveals that at pH 7·60 and above Va rearranges more rapidly than Ia, although the latter undergoes ring- opening ca . 30 times as fast as the former. In each of both compounds ring-opening proceeds at a rate proportional to hydroxide ion concentration below pH 8·5 and above pH 11, with a plateau between the two values. These results are consistent with attack by the hydroxide ion on both the protonated and neutral species of the adenine derivatives.

Purines—III : Rearrangement of 1-alkoxy-9-alkyladenines to 6-alkoxyamino-9-alkylpurines through isolable N′-alkoxy-1-alkyl-5-formamidoimidazole-4-carboxamidines

Abstract The Dimroth rearrangement of 1-alkoxy-9-alkyladenines (Ia,b,c,d) to 6-alkoxyamino-9-alkylpurines (IIa, b, c, d) was readily effected by treating the free bases (I) with boiling water. On the other hand, treatment of the 1-alkoxy derivatives (Ia, b, c) with water at a lower temperature produced N′-alkoxy-1-alkyl-5-formamidoimidazole-4-carboxamidines (IVa, b, c), the intermediates in the Dimroth rearrangements, in good yields. When heated in water, IVa, b,c were recyclized to the rearranged products (IIa, b, c) with formation of a trace of the reversion products (Ia, b,c). The reaction of I with hot aqueous alkali afforded N′-alkoxy-1-alkyl-5-aminoimidazole-4-carboxamidine (III), the deformylated product of IV, and a small amount of the rearranged product (II). Treatment of IVc with alkali also gave IIIc and a small amount of IIc, whereas the reaction with acid resulted in the rapid reversion to Ic.