Novel examples of electrophilic rearrangement of substituted pyrimidin-4-ones under Vilsmeier-Haack reaction condition

Abstract

The critical influence of the size of aliphatic annulated cycles in 2,2-disubstituted pyrimidin-4-ones on the conditions of rearrangement under the action of Vilsmeier-Haack reagent was established. Compounds with a 5-membered ring cycle to pyrimidin-4-one require heating at 1100C for 2 h due to the coplanar arrangement of dimethyliminium and chloriminium groups in intermediates, which leads to placement of a positive charge on the nitrogen atom of the dimethylamino group, which is unfavorable for the reaction. In the case of 6- and 7-membered annulated cycles, there is interatomic repulsion in the intermediates from the hydrogen atoms of methyl and methylene groups, as well as hydrogen atoms of CH and NH, which contributes to placement of a positive charge on the endocyclic atom of nitrogen and chloriminium salt and easier rearrangement. The size of aliphatic annealed and spirocycles to the pyrimidine framework affects not only the reaction conditions but also the formation of products.