Study of the interaction of benzene-1,4-dicarboxamide with methylmalonyl dichloride

Studies show that compounds such as 1,3-oxazine-6-ones are promising starting reagents that allow to obtain various acyclic and heteroaromatic systems. These substances demonstrate a wide range of biological activity. Meanwhile, it is known that depending on 1,3-oxazine cycles number in molecule, pharmacological activity may vary. Therefore, purpose of our work was to study reaction of benzene-1,4-dicarboxamide with methylmalonyl dichloride as the most rational way to obtain new compounds of given structure. This interaction can potentially lead to both mono- and bis(1,3-oxazine-6-one) derivatives. Reaction between terephthalamide and methylmalonyl dichloride was conducted at their equimolar ratio and with twofold excess of the latter. Syntheses were carried out in two media: absolute benzene and 1,2-dichloroethane. Reaction of equimolar amounts of reagents resulted in obtaining the only product 4-(4-hydroxy-5-methyl-6-oxo-6H-1,3-oxazine-2-yl)benzamide (1). In twofold excess of methylmalonyl dichloride, just product 1 was obtained after 24 hours of refluxing and after 58 hours only 2,2'-(benzene-1,4-diyl)bis(4-hydroxy-5-methyl-6H-1,3-oxazine-6-one) (2) formed. Determination of partial negative charge on nitrogen atoms of amido groups of terephthalamide and compound 1 allowed us to confirm sequential formation firstly of mono- (1) and then bis(1,3-oxazine-6-one) derivative (2) in reaction mass. Structure of obtained compounds was proved by NMR spectroscopy on ¹H and ¹³C nuclei. When studying solvent influence on synthesis rate, no significant differences were noted between benzene and 1,2-dichloroethane. However, the yield of 2,2'-(benzene-1,4-diyl)bis(4-hydroxy-5-methyl-6H-1,3-oxazine-6-one) during synthesis in 1,2-dichloroethane was lower – 77% compared with 85% in benzene.