Purines. XLI. An alternative synthesis and the chemical behavior of 7,9-dialkyladeninium salts.

Abstract

A full account is given of the chemical behavior observed for 7, 9-dialkyladeninium salts (16). On treatment with boiling 1N aqueous NaOH for 60min, 16a, b, d, e (X=I), 16c (X=Br), and 16f (X=ClO4) rearranged to isomeric N6, 7-dialkyladenines (21a-f) in 50-91% yields. Treatment of the salts with 0.5N aqueous Na2CO3 at room temperature for 30-90min or with Amberlite CG-400 (OH-) in H2O at room temperature gave the ring-opened derivatives 22a-f (in the trans-formamide form) in 56-83% yields, and rate constants for the ring-opening reactions of 16a, b, d-g (X=ClO4) and 16c (X=Br) leading to 22a-g were determined in H2O at pH 9.84 and ionic strength 0.50 at 25°C. Cyclization of 22a with NaH in AcNMe2 at room temperature or with boiling 1N aqueous NaOH produced 21a in 84% or 72% yield, respectively.In solution, the trans-formamides 22 seemed to transform slowly into the cis-formamides 23, attaining equilibria. The existence of such an equilibrium in D2O or Me2SO-d6 at 25°C or in H2O at pH 9.84 and ionic strength 0.50 at 25°C was kinetically confirmed in the case of 22a, and the mechanism of the rearrangement of 16 to 21 through 22 is discussed on the basis of the above kinetic results and Deslongchamps' theory of stereoelectronic control. On treatment with NaBH4 in MeOH at room temperature, 16a (X=I) furnished the 7, 8-dihydro derivative 28 (84% yield), which slowly decomposed in H2O at 60°C to give 22a in 49% yield.The 7, 9-dialkyladeninium salts (16) were found to be obtainable from N'-alkoxy-1-alkyl-5-formamidoimidazole-4-carboxamidines (9) through an alternative synthetic route : Alkylations of 9 with alkyl halides in HCONMe2 in the absence of base, followed by hydrogenolysis of the N'-alkoxy group and cyclizatio (or vice versa) produced 16 in acceptable yields. In order to interpret the proton nuclear magnetic resonance spectrum of 22a, the 2-deuterated species 26 was also synthesized from 24 via 25 and 27.