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Commercial-Scale Visible Light Trifluoromethylation of 2-Chlorothiophenol Using CF <sub>3</sub> I Gas

Kaid C. Harper, En-xuan Zhang, Zhiqing Liu, Timothy Grieme, Timothy B. Towne, Daniel J. Mack, Jeremy Griffin, Song-yuan Zheng, Ningning Zhang, Srinivas Gangula, Jia-Long Yuan, Robert J. Miller, Pingzhong Huang, James R. Gage, Moiz Diwan, Yi‐Yin Ku

2022Organic Process Research & Development33 citationsDOI

Abstract

Despite the growth of photoredox methods in academia, application of photoredox at scale in the pharmaceutical and fine chemical industries has been slow. In this report, a photoredox trifluoromethylation of a thiophenol was modified from the original literature report, and the mechanism was investigated to define the key scale-up parameters. The mechanistic insight was leveraged in the design and execution of two different reactor designs: an LED-based plug flow photoreactor and a laser-based continuous stirred tank photoreactor. In one of the first examples of commercial-scale photoredox chemistry, the process was scaled to provide over 500 kg of the desired intermediate and amended to fully continuous manufacturing.

Topics & Concepts

TrifluoromethylationPhotoredox catalysisThiophenolFlow chemistryProcess engineeringPhotocatalysisPlug flowChemistrySCALE-UPScale (ratio)Continuous flowCombinatorial chemistryPhotochemistryComputer scienceNanotechnologyMaterials scienceBiochemical engineeringOrganic chemistryCatalysisEngineeringPhysicsThermodynamicsAlkylTrifluoromethylClassical mechanicsQuantum mechanicsFluorine in Organic ChemistryAdvanced Photocatalysis TechniquesRadical Photochemical Reactions
Commercial-Scale Visible Light Trifluoromethylation of 2-Chlorothiophenol Using CF <sub>3</sub> I Gas | Litcius