Approaches to the synthesis of new symmetrical bridged bis(6-hydroxypyrimidin-4(3H)-ones)

Introduction. The synthesis of new symmetrical bridged bis(6-hydroxypyrimidin-4(3H)-ones) is of significant interest in modern chemistry and pharmaceuticals. Due to their unique structure, such systems have the potential to create new drugs with improved pharmacological properties. They are widely known for their antiviral, antitumor, and antibacterial properties, making them attractive candidates for the development of new therapeutic agents.
This work considers two approaches to the synthesis of new bis(6-hydroxypyrimidin-4(3H)-ones) with aromatic and aliphatic linkers.
Methods. Bis(6-hydroxypyrimidin-4(3H)-ones) (1 a-c), substituted with an aromatic 1,4-phenylene bridge at the 2,2' positions, were obtained by the reaction of N'¹,N'⁴-diphenylbenzene-1,4-dicarboximidamide with an excess of 2-substituted malonylchlorides. The 5,5'-substituted derivatives of bis(6-hydroxypyrimidin-4(3H)-one) with a trimethylene bridge (2 a-c) were obtained through the interaction of N-phenylimidamides and tetraethyl propane-1,1,3,3-tetracarboxylate. The structure of the synthesized compounds was confirmed using ¹H and ¹³C NMR spectroscopy.
Results and Conclusions. The yield of 2,2'-(1,4-phenylene)bis(6-hydroxy-5-substituted-3-phenylpyrimidin-4(3H)-ones) (1 a-c) ranged from 34-71%. It was found that the substituent in the malonylchloride affects the yield of the products. Alkyl substituents facilitate the obtainment of target compounds with higher yields compared to the aromatic phenyl group. The yield of 5,5'-propane-1,3-diylbis(6-hydroxy-2-substituted-1-phenylpyrimidin-4(3H)-ones) (2 a-c) ranged from 58-72%. It was discovered that the presence of aliphatic substituents in N-phenylimidamide leads to the obtainment of these compounds with higher yields compared to the use of N-phenylbenzocarboximidamide.