Highly efficient and clean synthesis of 1-amino-2-acetylanthraquinone by copper-catalyzed reductive cleavage of isoxazole motif

Abstract

A clean and highly efficient synthesis of 1-amino-2-acetylanthraquinone via reductive isoxazole ring cleavage of 3-methylanthra[1,2- c ]isoxazole-6,11-dione catalyzed by trace copper using hydrazine hydrate as a clean reducing agent and water as a green reaction medium under mild reaction conditions was investigated. Various transition-metal catalysts were screened for the reductive ring-opening reaction, and Cu(NO 3 ) 2 was shown to be an excellent catalyst. A conversion of 97.2% and 1-amino-2-acetylanthraquinone selectivity greater than 95% were obtained in the presence of 2.6 mol% Cu(NO 3 ) 2 (turnover number 38) with 1.3 equiv. of hydrazine hydrate for 2 h in water. The structure of the product was confirmed by 1 H nuclear magnetic resonance spectroscopy and mass spectrometry; the main byproduct was hydroxyl-substituted 1-amino-2-acetylanthraquinone. A possible reaction mechanism for the copper-catalyzed ring cleavage of 3-methylanthra[1,2- c ]isoxazole-6,11-dione with hydrazine hydrate was proposed. A trace-copper-catalyzed reductive isoxazole-ring-cleavage strategy for clean and highly efficient production of 1-amino-2-acetylanthraquinone under mild reaction conditions was presented.