Reactions of 3-Arylisocoumarins with N-Nucleophiles - A Route to Novel Azaheterocycles

Abstract

This review highlights the promising science that has arisen from the synthesis of novel azaheterocycles from isocoumarins. Specific topics include their synthesis and biological activity. Isocoumarins (1H-isochromen-1-ones) are promising synthons, in particular due to the presence of a deoxybenzoin fragment which opens up wide possibilities for synthetic transformations. The deoxybenzoin cycle is highly susceptible to the action of various nucleophilic agents; its oxygen atom participates in recyclization reactions under the action of N-nucleophiles where it is replaced by a nitrogen atom, making it possible to obtain isoquinolones via a reaction with ammonia, primary amines, hydroxylamine and benzodiazepinones via a reaction with hydrazine. We systematize literature data, including patents (about 60 publications in all), demonstrate the routes of 3- arylisocoumarins modification under the action of N-nucleophiles - ammonia and primary amines, diamines, secondary amines, (het)arylamines, hydroxylamine, and hydrazines, and discuss the practical importance of these studies for medicinal chemistry.

Keywords: 1H-isochromen-1-one; Benzodiazepinone; Isocoumarin; Isoquinolone; N-nucleophile; Nucleophilic reaction; Recyclization; Ring opening ring closure reaction.