Development and Scale-Up of a Novel Photochemical C–N Oxidative Coupling

Abstract

A visible light promoted C−N-coupling of a functionalized pyridazinone with veratrole was developed to forge the central C−N bond of an agrochemical intermediate. Dosing aqueous NaOCl and 4% O 2 in N 2 under blue light irradiation (460 nm)was key to promote the desired transformation while generating benign wastes. Mechanistic studies suggest the formation of a Nchloro species that undergoes selective coupling via a radical pathway induced by the combination of light and oxygen. Further development led to an optimized semi-batch process, which was successfully scaled up to an initial 20 L and then 1.2 m 3 .

Shining a Light on the Advances, Challenges and Realisation of Utilising Photoredox Catalysis in Pharmaceutical Development

“…Syngenta have also used immersion‐well‐type Peschl LED lamps to scaleup a photo‐initiated radical chain reaction (Figure 2c). [19] Scale up of this process was achieved using a reaction engineering study to observe the effect of mixing and dissolved oxygen concentration in addition to maintaining photon equivalents ( vide infra ) despite the non‐uniformity of light distribution throughout the vessel. Ultimately Syngenta were able to achieve 853 kg of target product using a 1.2 m 3 stirred tank reactor, demonstrating photochemical processes can be successfully scaled with good understanding of reaction and engineering parameters.…”

“…To alleviate many of the concerns associated with metalbased PRCs, organic photoredox catalysts [43] such as dyes [19,44] quinones, pyryliums, and phenylene derivatives [45] are being explored as viable alternatives. As with their metal-based counterparts, the properties of organic PRCs can be tuned to provide the desired photoreducing or photooxidising power and innately possess high stability against photodegradation.…”

Membrane-based TBADT recovery as a strategy to increase the sustainability of continuous-flow photocatalytic HAT transformations

“…the scale-up needs of photochemical reactions, as was highlighted in several examples of large-scale photochemical reactions carried out in continuous-flow systems 11,[26][27][28][29][30][31][32][33][34][35] . For the removal of the catalyst, organic solvent nanofiltration (OSN) could be a suitable strategy for catalyst recovery in continuous-flow systems.…”

Dynamically triggering photoreactions for high performance and efficiency

“…Various reactor designs have been shown to be scalable and were applied on industrial scale. [35][36][37]…”