Optimization of a Scalable Photochemical Reactor for Reactions with Singlet Oxygen Konstantin N. Loponov, † Joao Lopes, † Maciej Barlog, ‡ Ekaterina V. Astrova, § Andrei V. Malkov, ∥ and Alexei A. Lapkin* ,† † Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB2 3RA, United Kingdom ‡ School of Chemistry, Glasgow University, Glasgow G12 8QQ, United Kingdom § Ioffe Physico-Technical Institute, St. Petersburg 194021, Russian Federation ∥ Department of Chemistry, Loughborough University, Loughborough LE11 3TU, United Kingdom * S Supporting Information ABSTRACT: Oxygenation of α-pinene using photochemically generated singlet oxygen ( 1 O 2 ) was studied in detail in several continuous flow photochemical reactors. Ferrioxalate actinometry and reaction kinetic data were used to compare light sources and reactor geometries, such as the immersed-well, an annular recirculating and microfluidic reactors. It is shown that reactor miniaturization, control of intensity and of spectral composition of light, and elevated oxygen pressure are the crucial factors for safe and efficient photo-oxygenation reactions. Higher quantum yields were generally obtained with the microreactor-LED assemblies due to better energy utilization, compared to all other systems studied. For the single-phase microreactor-LED system, an optimization model has been developed that revealed a broad optimal design window. ■ INTRODUCTION Even though there are several large-scale industrial photo- chemical processes, their number is comparatively low due to the generally poor economics and complex scalability and safety issues of many photochemical transformations. Reactions with photochemical activation are not easily scalable mainly due to inefficient utilization of light and poor heat/mass transfer rates in large-volume reactors, as well as low power-to-photon efficiency of artificial light sources. 1 At the same time, there are a number of reactions of high synthetic relevance that are frequently used in organic chemistry on the preparative scale, which would benefit from availability of readily scalable photochemical technology. A significant advance was made recently in scaling photo- chemical reactions through development of tubular flow reactors. 2 An important contribution to this topic is a recent development of photochemical oxidation of artemisinic acid to artemisinin by Seeberger et al. 3 Such examples show the potential of flow approaches to develop scalable and efficient photochemical processes. Another scalable reactor platform for photochemistry is the compact and microstructured flow reactor technology. 4 Good heat management and radical quenching in small channels of microreactors allow safe exploitation of hazardous reactions, while also enabling optimal light absorption. Efficient, high- power LEDs with high photon fluxes, a wide range of available wavelengths, and long lifetime offer interesting new oppor- tunities for optimization of the reactor design, especially in combination with microreactors. Although microstructured reactors were successfully exam- ined in a wide range of applications of organic chemistry, including photochemistry, 1b,5 no generalized design principles of photochemical microreactors were reported to date. In this study, we focus on the application of microreactor technology in singlet oxygen ene reactions. 6 We compare efficiencies of light utilization for several light sources, including conventional and LED lamps in several photoreactors, namely, an immersed well, annular recirculating reactor, and a silicon microreactor unit. These were tested in various lamp−reactor configurations and in different operation modes, summarized in Figure 1. As a case study we investigated oxygenation of α- pinene to pinocarvone, as in Figure 2. Pinocarvone is used as a building block in many syntheses, including synthesis of antimalarial peroxides and chiral ligands for catalysis. 7 Finally, we generalize the fundamental principles for design and optimization of scalable photochemical reactors. As far as we are aware, this is the first systematic study of operational parameters of continuous flow photochemistry, presenting a detailed optimization study. ■ EXPERIMENTAL SECTION Annular Flow Reactor and Lamps. A description of the annular recirculating photoreactor rig can be found elsewhere. 8 In this study we used an improved reactor design with an annular porous glass membrane introduced at the bottom of the reactor for better gas dispersion. A circular lamp (peak wavelength λ at 524 nm) was assembled from 10 strips of 24 LEDs each, providing a 15 cm long illumination zone. A fluorescent lamp (λ = 420 nm) consisting of two U-shaped actinic fluorescent bulbs (24 W, 23 cm illumination length, Catalina Aquarium) surrounded by aluminum cylindrical Special Issue: Continuous Processes 14 Received: June 5, 2014 Published: August 8, 2014 Article pubs.acs.org/OPRD © 2014 American Chemical Society 1443 dx.doi.org/10.1021/op500181z | Org. Process Res. Dev. 2014, 18, 1443−1454