Continuous Flow Synthesis of Azoxybenzenes by Reductive Dimerization of Nitrosobenzenes with Gel‐Bound Catalysts

Abstract

In the search for a new synthetic pathway for azoxybenzenes with different substitution patterns, an approach using a microfluidic reactor with gel‐bound proline organocatalysts under continuous flow is presented. Herein the formation of differently substituted azoxybezenes by reductive dimerization of nitrosobenzenes within minutes at mild conditions in good to almost quantitative yields is described. The conversion within the microfluidic reactor is analyzed and used for optimizing and validating different parameters. The effects of the different functionalities on conversion, yield, and reaction times are analyzed in detail by NMR. The applicability of this reductive dimerization is demonstrated for a wide range of differently substituted nitrosobenzenes. The effects of these different functionalities on the structure of the obtained azoxyarenes are analyzed in detail by NMR and single‐crystal X‐ray diffraction. Based on these results, the turnover number and the turnover frequency were determined.

Catalytic selective oxidation of aromatic amines to azoxy derivatives with an ultralow loading of peroxoniobate salts

“…12 In general, azoxy compounds can be prepared either by reductive homodimerization of nitroarenes or oxidative coupling of aromatic amines. 13,14 For the reduction route, supported Au nanocatalysts were reported to display a high selectivity toward azoxybenzene. 15,16 Later on, ceriastabilizing Ni-Ni δ+ clusters, Ru single atom materials, etc.…”

Direct Asymmetric Aldol Reaction in Continuous Flow Using Gel‐Bound Organocatalysts

“…Thus immobilization of tertiary amines as catalysts in surface‐bound gels is also possible and offers access to a wide range of Knoevenagel reactions under continuous flow conditions [19] . In addition, the immobilization of proline derivatives is also possible, which opens up access to rather unusual adducts such as aromatic azoxy compounds under mild reaction conditions [20] …”

“…[19] In addition, the immobilization of proline derivatives is also possible, which opens up access to rather unusual adducts such as aromatic azoxy compounds under mild reaction conditions. [20]…”

“…An immobilization within crosslinked polymer networks enables reactions inside of swollen, three‐dimensional textures, which in contrast to solid particles, increases the amount of immobilized and accessible catalyst from surface area to bulk volume [16,17] . The general applicability of surface‐bound gels with a high crosslinker content as carriers of catalysts and enzymes in MFRs, has already been shown recently [18–20] . In all three cases, hexagonally ordered gel arrays, immobilized on glass slides, were obtained via photolithography, and used for various reactions within MFRs.…”

“…[16,17] The general applicability of surface-bound gels with a high crosslinker content as carriers of catalysts and enzymes in MFRs, has already been shown recently. [18][19][20] In all three cases, hexagonally ordered gel arrays, immobilized on glass slides, were obtained via photolithography, and used for various reactions within MFRs. Thus immobilization of tertiary amines as catalysts in surface-bound gels is also possible and offers access to a wide range of Knoevenagel reactions under continuous flow conditions.…”