Reaction Isatoic Anhydride Synthesis Of Palladium-catalyzed Carbonylation Of O-iodoaniline

Isatoic anhydride (2H-3,1-benzoxazine-2,4-(1H)-dione) is an extremely versatile compound. Due to its own structural characteristics, it is easy to react with electrophiles and nucleophiles, its analogs and derivatives have been widely used in agrochemicals, pharmaceuticals and fine chemicals, etc. Conventional methods for the synthesis of substituted isatoic anhydrides involve cyclization of anthranilic acid by highly toxic chloroformate or triphosgene, oxidation of isatin and rearrangement of phthalic acid derivatives. The reaction is limited in substrates scope and proceeds under harsh conditions. Hence, developing a novel and environmently friendly method for synthesis isatoic anhydride under mild condition is high desirable.Over the past decades, transition-metal catalyzed carbonylations with CO as a C1source have been demonstrated as one of the most powerful tools for the synthesis of various of carbonyl compounds. Especially, palladium-catalyzed carbonylation of aryl halides has been widely applied to synthesize aromatic esters, amides and ketones in both academic and industrial communities. Recently, carbonylation with a subsequent intramolecular cyclization reaction has been illustrated as an efficient process for the straightforward synthesis of heterocycles. However, the double carbonylation of o-iodoanilines for direct synthesis of isatoic anhydrides which are a class of valuable chemicals and versatile building blocks has not yet been realized. In this paper, we have developed a novel palladium-catalyzed oxidative double carbonylation of o-iodoanilines for the synthesis of N-unsubstituted isatoic anhydrides.