Effect of the Amount of Sodium Ethoxide on the Direction of Cyclization in Reactions of Amidines with Ethoxymethylene Acetoacetate

Abstract

Recyclization of pyrimidines occurring with substitution of the endocyclic carbon atom C(4) by a nonring carbon atom of the 5-ethoxycarbonyl group was reported earlier in [1, 2]. Such a rearrangement was classified as C–C recyclization of pyrimidines, in contrast to N–N recyclization (the Dimroth rearrangement) [3] and N–C recyclization (the Kost–Sagitullin rearrangement) [4]. In studying the condensation of hydrochlorides of acetamidine (1a) and phenylacetamidine (1b) with ethoxymethylene acetoacetate in the presence of sodium ethoxide, we noted that the amount of sodium ethoxide has a considerable effect on the direction of heterocyclization. We found that for an equimolar ratio of the amidines, ethoxymethylene acetoacetate, and sodium ethoxide, we obtain 5-ethoxycarbonyl-2-methyl(2-benzyl)4-methyl-pyrimidines 2a,b in high yield; while for a two-fold excess of sodium ethoxide relative to the amounts of the reagents used, 5-acetyl-4-hydroxy-2-methyl(2-benzyl)pyrimidines 3a,b are formed. We hypothesize that in the case of an excess of sodium ethoxide, as for an equimolar ratio of the reagents, the reaction initially occurs with formation of compounds 2. However, during treatment, the base formed in the presence of water (for excess sodium ethoxide) leads to recyclization of compounds 2 to form pyrimidines 3.