Flow Photochemistry

Photochemistry has seen renewed interest in recent years, but one classical problem that has remained is how to scale photochemical transformations. Scalability is severely hampered due to the attenuation effect of photon transport (Beer-Lambert law), which prevents the use of a dimension-enlarging strategy for scale-up. If larger reactors are used, over-irradiation of the reaction mixture can become an important issue as the reaction times are substantially increased, often resulting in the formation of byproducts. The use of continuous-flow microreactors for photochemical applications allows overcoming most of the issues associated with batch photochemistry. The narrow channel of a typical microreactor provides opportunities to ensure a uniform irradiation of the entire reaction mixture. Consequently, photochemical reactions can be accelerated substantially and the formation of byproducts can be minimized. While on lab scale many successful examples of flow photochemistry have been demonstrated in recent years, concepts for a scale-up to industrially relevant quantities are scarce. Research in our laboratories focuses not only on novel flow photochemistry but also on developing a modular scalable flow photochemistry platform for both UV and visible light irradiation that can address monophasic and multiphasic chemistry of relevance to the synthesis of APIs.


Key Publications

Review: Recent Advances towards Sustainable Flow Photochemistry
J. D. Williams, C. O. Kappe, Curr. Opin. Green Sust. Chem. 2020, 10, 100351. DOI: 10.1016/j.cogsc.2020.05.001

Multi-kilogram per Hour Continuous Photochemical Benzylic Brominations Applying a Smart Dimensioning Scale-up Strategy
A. Steiner, P. M. C. Roth, F. J. Strauss, G. Gauron, G. Tekautz, M. Winter, J. D. Williams, C. O. Kappe Org. Process Res. Dev. 2020, 24, 2208−2216. DOI: 10.1021/acs.oprd.0c00239

Visible Light-Promoted Beckmann Rearrangements: Separating Sequential Photochemical and Thermal Phenomena in a Continuous Flow Reactor
Y. Chen, D. Cantillo, C. O. Kappe, Eur. J. Org. Chem. 2019, 25, 2163–2171. DOI: 10.1002/ejoc.201900231

Finding the Perfect Match: A Combined Computational and Experimental Study Towards Efficient and Scalable Photosensitized [2+2] Cycloadditions in Flow
J. D. Williams, M. Nakano, G. Romaric, J. A. Rincon, O. de Frutos, C. Mateos, J. C. M. Monbaliu, C. O. Kappe, Org. Process Res. Dev. 2019, 23, 78-87. DOI: 10.1021/acs.oprd.8b00375

Visible-Light Photoredox Catalysis using a Macromolecular Ruthenium Complex: Reactivity and Recovery by Size-Exclusion Nanofiltration in Continuous Flow
J. Guerra, D. Cantillo, C. O. Kappe, Catal. Sci. Technol. 2016, 6, 4695-4699. DOI: 10.1039/c6cy00070c

Safe Generation and Use of Bromine Azide under Continuous Flow Conditions  ̶  Selective 1,2-Bromoazidation of Olefines
D. Cantillo, B. Gutmann, C. O. Kappe, Org. Biomol. Chem. 2016, 14, 853-857. DOI: 10.1039/c5ob02425k

Light-Induced C−H Arylation of (Hetero)arenes via In Situ Generated Diazo Anhydrides
D. Cantillo, C. Mateos, J. A. Rincon, O. de Frutos, C. O. Kappe, Chem. Eur. J. 2015, 21, 12894-12898. DOI: 10.1002/chem.201502357

Singlet Oxygen Oxidation of 5-Hydroxymethylfurfural (5-HMF) in Continuous Flow.
T. S. A. Heugebaert, C. V. Stevens, C. O. Kappe, ChemSusChem 2015, 8, 1648-1651. DOI: 10.1002/cssc.201403182

Continuous Flow alpha-Trifluoromethylation of Ketones by Metal Free Visible Light Photoredox Catalysis.
D. Cantillo, O. de Frutos, J. A. Rincon, C. Mateos , C. O. Kappe, Org. Lett. 2014, 17, 5590-5593. DOI: 10.1021/ol403650y

A Scalable Procedure for Light Induced Benzylic Brominations in Continuous Flow.
D. Cantillo, O. de Frutos, J. A. Rincon, C. Mateos , C. O. Kappe, J. Org. Chem. 2014, 79, 223-229. DOI: 10.1021/jo402409k

A Continuous Flow Protocol for Light-Induced Benzylic Fluorination.
D. Cantillo, O. de Frutos, J. A. Rincon, C. Mateos , C. O. Kappe, J. Org. Chem. 2014, 79, 8486-8490. DOI: 10.1021/jo5016757

Continuous Flow Synthesis of beta-Amino Acids from alpha-Amino Acids via Arndt-Eistert Homologation.
V. D. Pinho, B. Gutmann, C. O. Kappe, RSC Adv. 2014, 4, 37419-37422. DOI: 10.1039/c4ra08113g

Continuous-flow Production of Photocatalytically Active Titanium Dioxide Nanocrystals and its Application to the Photocatalytic Addition of N,N-Dimethylaniline to N-Methylmaleimide.
M. Baghbanzadeh, T. N. Glasnov, C. O. Kappe, J. Flow Chem. 2013, 3, 109-113. DOI: 10.1556/JFC-D-13-00018