Exploring New Parameter Spaces for the Oxidative Homocoupling of Aniline Derivatives: Sustainable Synthesis of Azobenzenes in a Flow System

Abstract

Aromatic azo compounds have countless applications, not merely in the chemical industry, but also in medicinal chemistry, biotechnology, and the field of renewable resources. However, in the synthetic batch routine, the synthesis of azobenzenes often constitutes a significant challenge, mainly because of the ease of overreaction leading to nonoptimal selectivity, and also because of reactivity issues necessitating long reaction times and special reaction conditions. We therefore exploited the benefits of continuous-flow processing for the copper-mediated oxidative homocoupling of arylamines to facilitate the time-, cost-, and atom-effective synthesis of azobenzenes. The novel process window of increased temperature and pressure ranges in combination with the application of overheated solvents afforded a remarkable chemical intensification. Precise control of the residence time restricted the possibility of undesired reaction pathways, such as overreaction to azoxy products, but at the same time ensured sufficient reactivity to furnish valuable aromatic azo compounds, even in the cases of deactivated halogen-substituted anilines and multisubstituted derivatives. As compared with earlier batchwise syntheses, the designed process displays significant advances in terms of sustainability and productivity.

Renewable Electricity Enables Green Routes to Fine Chemicals and Pharmaceuticals

“…More attractively, due to the distinctive operation of continuous laminar flow in microreactors, unstable species can more easily be controlled than when produced in the traditional batch reactor. Hence, unstable and demanding species may be readily achieved in highly selective reactions [114] …”

“…Hence, unstable and demanding species may be readily achieved in highly selective reactions. [114] For the investigation of the electrochemical carboxylation of benzylic halides, new microreactors have been prepared and comprise of different cathode metals and distances between electrodes. Then at constant current, screening of the electrolysis of benzylic halides was carried out in a flow microreactor with Pt plates as both electrodes and appropriate distances between them.…”

Harnessing the Versatility of Continuous-Flow Processes: Selective and Efficient Reactions

“…Since CF chemistry appeared to be a reasonable strategy for the production of valuable aromatic azo compounds, we explored the oxidative homocoupling of arylamines in a CF system, employing copper powder as a cheap and readily available source for catalytically active species (Figure ) 67…”

Photocatalytically Active Conjugated Porous Polymers via Click Chemistry for Heterogeneous Dehydrogenation of Hydrazo Aromatics

“…Aromatic azo compounds are an important class of raw materials and are widely used as dyes and pigments, free radical initiators, photoresponsive functional devices, food additives, therapeutic agents, and indicators. − Due to the high value of aromatic azo compounds, great effort has been made for the synthesis of aromatic azo compounds. Classical methods include reductive coupling of aromatic nitro compounds, − oxidative couplings of anilines, − electrophilic reactions of diazonium salts with aromatic compounds, , and Mills reaction . In addition, a straightforward route that involves the direct dehydrogenation of hydrazo aromatics could not be ignored .…”