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 us to obtain various acyclic and heteroaromatic systems. These substances demonstrate a wide range of biological activity. Meanwhile, it is known that depending on the 1,3-oxazine cycle number in the molecule, pharmacological activity may vary. Therefore, the purpose of our work was to study the reaction of benzene-1,4-dicarboxamide with methylmalonyl dichloride, as a rational way to obtain new compounds of a given structure. This interaction can potentially lead to both mono- and bis(1,3-oxazine-6-one) derivatives. The reaction between terephthalamide and methylmalonyl dichloride was conducted at an equimolar ratio, with a twofold excess of the latter. Syntheses were carried out in two media—absolute benzene and 1,2-dichloroethane. The reaction of equimolar amounts of reagents resulted in obtaining only one product—4-(4-hydroxy-5-methyl-6-oxo-6H-1,3-oxazine-2-yl)benzamide (1). In twofold excess of methylmalonyl dichloride, only product 1 was obtained after 24 h of refluxing; after 58 h, only 2,2′-(benzene-1,4-diyl)bis(4-hydroxy-5-methyl-6H-1,3-oxazine-6-one) (2) was formed. The determination of the partial negative charge on the nitrogen atoms of the amido groups of terephthalamide and compound 1 allowed us to confirm the sequential formation firstly of the mono- (1) and then the bis(1,3-oxazine-6-one) derivative (2) in the reaction mass. The structure of the obtained compounds was proven using NMR spectroscopy on 1H and 13C nuclei. When studying solvent influence on the 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.