Yuanhai Su

Photochemical Transformations Accelerated in Continuous‐Flow Reactors: Basic Concepts and Applications

Continuous-flow photochemistry is used increasingly by researchers in academia and industry to facilitate photochemical processes and their subsequent scale-up. However, without detailed knowledge concerning the engineering aspects of photochemistry, it can be quite challenging to develop a suitable photochemical microreactor for a given reaction. In this review, we provide an up-to-date overview of both technological and chemical aspects associated with photochemical processes in microreactors. Important design considerations, such as light sources, material selection, and solvent constraints are discussed. In addition, a detailed description of photon and mass-transfer phenomena in microreactors is made and fundamental principles are deduced for making a judicious choice for a suitable photomicroreactor. The advantages of microreactor technology for photochemistry are described for UV and visible-light driven photochemical processes and are compared with their batch counterparts. In addition, different scale-up strategies and limitations of continuous-flow microreactors are discussed.

A convenient numbering-up strategy for the scale-up of gas–liquid photoredox catalysis in flow

Visible-light photocatalysis is a mild activation method for small molecules and enables a wide variety of transformations relevant for organic synthetic chemistry. However, one of the limitations of photocatalysis and photochemistry in general is the limited scalability due to the absorption of light (Lambert–Beer law). Here, we report the development of a convenient numbering-up strategy for the scale-up of gas–liquid photocatalytic reactions in which the gas is consumed. Only commercially available constituents were used and the system can be rapidly assembled by any practitioner of flow chemistry. The modular design allows us to systematically scale the photochemistry within 2n parallel reactors (herein, n = 0, 1, 2, 3). The flow distribution in the absence of reactions was excellent, showing a standard deviation less than 5%. Next, we used the numbered-up photomicroreactor assembly to enable the scale-up of the photocatalytic aerobic oxidation of thiols to disulfides. The flow distribution was again very good with a standard deviation lower than 10%. The yield of the target disulfide in the numbered-up assemblies was comparable to the results obtained in a single device demonstrating the feasibility of our approach.

Beyond organometallic flow chemistry : the principles behind the use of continuous-flow reactors for synthesis

Flow chemistry is typically used to enable challenging reactions which are difficult to carry out in conventional batch equipment. Consequently, the use of continuous-flow reactors for applications in organometallic and organic chemistry has witnessed a spectacular increase in interest from the chemistry community in the last decade. However, flow chemistry is more than just pumping reagents through a capillary and the engineering behind the observed phenomena can help to exploit the technology’s full potential. Here, we give an overview of the most important engineering aspects associated with flow chemistry. This includes a discussion of mass-, heat-, and photon-transport phenomena which are relevant to carry out chemical reactions in a microreactor. Next, determination of intrinsic kinetics, automation of chemical processes, solids handling, and multistep reaction sequences in flow are discussed. Safety is one of the main drivers to implement continuous-flow microreactor technology in an existing process and a brief overview is given here as well. Finally, the scale-up potential of microreactor technology is reviewed.

Accelerated gas-liquid visible light photoredox catalysis with continuous-flow photochemical microreactors

In this protocol, we describe the construction and use of an operationally simple photochemical microreactor for gas-liquid photoredox catalysis using visible light. The general procedure includes details on how to set up the microreactor appropriately with inlets for gaseous reagents and organic starting materials, and it includes examples of how to use it to achieve continuous-flow preparation of disulfides or trifluoromethylated heterocycles and thiols. The reported photomicroreactors are modular, inexpensive and can be prepared rapidly from commercially available parts within 1 h even by nonspecialists. Interestingly, typical reaction times of gas-liquid visible light photocatalytic reactions performed in microflow are lower (in the minute range) than comparable reactions performed as a batch process (in the hour range). This can be attributed to the improved irradiation efficiency of the reaction mixture and the enhanced gas-liquid mass transfer in the segmented gas-liquid flow regime.

A mechanistic investigation of the visible light photocatalytic trifluoromethylation of heterocycles using CF3I in flow

Photocatalytic radical trifluoromethylation strategies have impacted the synthesis of trifluoromethyl-containing molecules. However, mechanistic aspects concerning such transformations remain poorly understood. Here, we describe in detail the mechanism of the visible-light photocatalytic trifluoromethylation of N-methylpyrrole with gaseous CF3 I in flow. The use of continuous-flow microreactor technology allowed for the determination of different important parameters with high precision (e.g., photon flux, quantum yield, reaction rate constants) and for the handling of CF3 I in a convenient manner. Our data indicates that the reaction occurs through a reductive quenching mechanism and that there is no radical chain process present.

A simple and efficient synthesis protocol for sulfonation of nitrobenzene under solvent-free conditions via a microreactor

A simple and efficient method for the sulfonation of nitrobenzene using SO3 as the sulfonating agent in a microreactor was developed and conducted in this work. The reaction enthalpy was determined using a microreactor-based calorimeter. The effects of molar ratio of reactants, reaction temperature and liquid hourly space velocity (LHSV) on the reaction performance were experimentally studied under solvent-free conditions. Under optimized reaction conditions, 94% conversion of nitrobenzene (NB) and 88% yield of meta-nitrobenzenesulfonic acid (m-NBSA) was obtained even when the residence time was less than 2 s. A microreactor-batch set-up was fabricated and developed to completely convert NB. The process safety has been improved and reaction time has been reduced compared to the batch method. These results demonstrate that the multifunctional integrated microreactor is an extremely useful and highly efficient tool for the sulfonation of NB under solvent-free conditions.

A sensitivity analysis of a numbered-up photomicroreactor system

Limitations with regard to the scalability of photochemical reactions can be efficiently overcome by using numbered-up microreactor technology. Here, the robustness of such a numbered-up capillary photomicroreactor system is tested when subjected to potential disturbances, such as channel blockage and light source failure. Channel blockage leads to relatively large changes in both flow distribution and yield. However, we found that the performance can be accurately predicted thus making it possible to adjust the reaction parameters to obtain certain output targets. Light source failure did not lead to large variations in the mass flow distribution, highlighting the importance of the flow distributor section. Since the reaction is photocatalyzed, the impact on the reaction yield was significant in the reactor where the light failure occurred.