In‐situ Oxidation and Coupling of Anilines towards Unsymmetric Azobenzenes Using Flow Chemistry

Molecular switches, especially azobenzenes, are used in numerous applications, such as molecular solar thermal storage (MOST) systems and photopharmacology. The Baeyer‐Mills reaction of anilines and nitrosobenzenes has been established as an efficient synthetic method for non‐symmetric azobenzenes. However, nitrosobenzenes are not stable, depending on their substitution pattern and pose a health risk. An in‐situ oxidation of anilines with Oxone® was optimized under continuous flow conditions avoiding isolation and contact. The in‐situ generated nitrosobenzene derivatives were subjected to a telescoped Baeyer‐Mills reaction in flow. That way azobenzenes with a broad substituent spectrum were made accessible. Azobenzenes are often accessed via the Baeyer‐Mills reaction of an aniline with a nitrosobenzene. To minimize the hazards while working with such substances, we herein report an in‐situ preparation of a large scope of different nitrosobenzene derivatives. These were used in a telescoped Baeyer‐Mills reaction of unsymmetric azobenzenes.