Dihydropyrimidines. Part 6. 5-Acetyldihydropyrimidines via condensation of olefinic acetylacetones with amidines. Reinvestigation of Ruhemann's reaction

Abstract

The condensation of benzylideneacetylacetone and benzamidine, studied by Ruhemann in 1903, has been reinvestigated in detail, and several new reaction products have been isolated and identified. The influence of varying the conditions of reaction have been studied. By using an aprotic solvent (benzene) with azeotropic removal of the water released, for example, the reaction is directed towards formation of 5-acetyldihydropyrimidine (5a). This compound has been obtained in better yields with a two-step approach: initial preparation of the 5-acetyl-6-hydroxytetrahydropyrimidine intermediate (4a), followed by dehydration in acidic media. While this tetrahydropyrimidine in CDCl₃ solution most probably exists as a mixture of the 1,4,5,6-tetrahydro and 3,4,5,6-tetrahydro compounds, crystallization from acetone gave single crystals of 5-acetyl-6-hydroxy-3,4,5,6-tetrahydropyrimidine (4aB) and water in the ratio 2 : 1. Using the two-step procedure, other tetrahydro- and dihydro-pyrimidine derivatives have been prepared from m-nitrobenzylideneacetylacetone and benzamidine. The reaction has also been explored using acetamidine. All isolated 5-acetyldihydropyrimidines exist in the solid state in the 1,4-dihydro form. However, in solution amidinic tautomerism was observed, which also favours the 1,4-dihydro tautomer. These newly prepared dihydropyrimidines easily undergo oxidation to the corresponding pyrimidines. The mechanism of the basic deacetylation observed by Ruhemann in ethanolic solutions, affording the 5-unsubstituted dihydropyrimidine, is also discussed.