Cascade nitrosation and addition–elimination of nitroacetanilides for the highly efficient synthesis of 1,4,2,5-dioxadiazine derivatives

Abstract

A domino nitrosation and addition–elimination of nitroacetanilides with NaNO₂ and H₂SO₄ has been developed to synthesize a variety of 1,4,2,5-dioxadiazine-3,6-dicarboxamides in excellent yields. The substrate scope can be extended to aryl nitromethyl ketones. A cascade reaction mechanism is proposed and the conjugated aryl moiety is considered to help stabilize the aci-nitroso species, the key intermediates in the cascade reaction. The methodology is practical and efficient because it avoids the purification of the intermediates. The nitroacetanilides were prepared from nitroacetic acid and various anilines employing DCC–DMAP as coupling reagents, and this protocol also possesses advantages like easy handling and high yields.