Development of continuous flow processes for the oxidative preparation of nitrosoarenes

Abstract

Nitrosoarenes are widely used in organic synthesis and medicinal chemistry. Despite their low commercial availability, those compounds are bench stable and could be isolated after synthesis for further reactions. However, nitrosoarenes synthesis is challenging due to its lack of selectivity leading to cumbersome, time- and resource-intensive purification method. A lab-scale flow setup has been developed for the tungstate-catalyzed aniline oxidation by hydrogen peroxide to have better selectivities. This setup led to similar selectivities than in batch but remains interesting for its easy scalability. Computations were also performed to support the experimental part. With it, oxidation potentials were determined leading to a better understanding of the aniline reactivity. Based on those results, a temperature-oxidation potential scale was constructed and verified. This one is not linear and does not consider the steric effects. Thus, the o-substituted anilines would have another scale than the other substituted anilines. Moreover, an improvement of the scale is possible by preparing more nitrosoarenes under flow conditions.