Design and application of a modular and scalable electrochemical flow microreactor
Electrochemistry constitutes a mild, green and versatile activation method of organic molecules. Despite these innate advantages, its widespread use in organic chemistry has been hampered due to technical limitations, such as mass and heat transfer limitations which restraints the scalability of electrochemical methods. Herein, we describe an undivided-cell electrochemical flow reactor with a flexible reactor volume. This enables its use in two different modes, which are highly relevant for flow chemistry applications, including a serial (volume ranging from 88 μL/channel up to 704 μL) or a parallel mode (numbering-up). The electrochemical flow reactor was subsequently assessed in two synthetic transformations, which confirms its versatility and scale-up potential.
KeywordsElectrochemistry Flow chemistry Scalability Reactor
In the past few years, electrochemical transformations have received renewed interest from the synthetic community as a powerful activation mode to enable versatile organic transformations [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31]. The application of electrons as traceless reagents avoids the use of hazardous or toxic oxidants, providing milder and more sustainable processes [7, 8, 12, 19, 22]. In addition, key electrochemical parameters, such as electric current and potential, can be easily tuned, providing an improved functional group tolerance and selectivity compared to classical thermal approaches [1, 3, 7, 12]. Even though the advantages of electrochemistry appear numerous and many remarkable procedures have been developed employing this technique, many synthetic organic chemists have been discouraged to apply this technique. This can be attributed to the need for specialized equipment and to the knowledge gap of most researchers in this rather esoteric discipline [2, 9]. In addition, electrochemical setups are often affected by process-related problems, like mass- and heat-transfer limitations, and by electrodeposition of organic substances on the electrode surface [32, 33, 34, 35, 36, 37, 38, 39, 40]. These drawbacks limit the reproducibility of electrochemistry and can hamper dramatically both its widespread use and its scalability beyond a laboratory scale [2, 7, 9, 19].
From its advent in 2012, our laboratory has always been interested in the development and manufacturing of novel flow reactor technology to overcome technological limitations in organic synthetic chemistry, such as photochemistry [41, 42, 43, 44] and gas-liquid transformations [45, 46, 47, 48]. We felt consistently that a “Do-It-Yourself” (DIY) approach was beneficial as it leveraged a fundamental understanding of the technology . This further enabled us (i) to reduce the overall capital investment, (ii) to repair setups quickly, (iii) to customize the design to our specific needs and (iv) to exploit the technology at its full potential.
We anticipated that also electrochemistry required a technological impetus to overcome the hurdles as described above. Indeed, most of the limitations associated with organic electrochemistry can be overcome by performing electrochemical reactions in continuous-flow microreactors. Specifically, the confined dimensions of micro-flow reactors (up to 1 mm interelectrode gap) allows to reduce the Ohmic drop, to minimize the total amount of supporting electrolytes, and to increase mass transfer from the bulk solution to the electrode surface [32, 33, 34, 35, 36, 37, 38, 39, 40, 50, 51, 52, 53, 54]. In addition, due to the continuous nature of these reactors, generation of local hotspots can be prevented. For these reasons, several electrochemical continuous-flow reactors were developed, commercialized and successfully deployed in a wide variety of electrochemical reactions [32, 34, 35, 36, 37, 38, 39, 51, 55, 56, 57, 58, 59, 60, 61, 62]. However, despite these great advances, we felt that a cheap, scalable and modular electrochemical flow reactor was still missing. In this article, we disclose our efforts towards this specific goal and we benchmarked the electrochemical reactor in two relevant electrochemical transformations.
Results and discussion
flexible reactor volume which allows to carry out the reaction both at small and large scale;
variable spacing between the electrodes, which can be readily accessed through adjustment of the gasket thickness;
simple and flat electrode design to avoid complex machining requirements;
high modularity in combination with easy exchangeable components;
inexpensive and solvent-resistant reactor materials;
safe operation of the reactor where the wet part and the electric parts are adequately separated.
Flat rectangular-shaped plates (120 mm × 55 mm × 2 mm) were used as electrode material and could be readily fit into the PTFE casing. In order to avoid the use of complex and expensive electrodes (e.g. machined channels in the electrode plate), only small holes were drilled to establish the microfluidic connections. Between the electrodes, a PTFE gasket was placed which can be adjusted in thickness (dG = 0.25–0.5 mm are used in this manuscript) and shape, e.g. an open-channel gasket (110 mm length × 45 mm length) or an 8-channel gasket (106 mm length × 3 mm width per channel) (Fig. 2a–b).
To elucidate the average residence time in the individual reactor channels, flow rates ranging from 0.1 mL/min to 1.0 mL/min were evaluated. As shown in Fig. 3, the volume of the individual channels averaged around 88 μL and 164 μL for the 0.25 mm and 0.5 mm thick gasket, respectively. The small differences between the channels can be attributed to the positioning of the flexible PTFE gasket upon closing the reactor. The standard deviation measured for both gaskets was below 10% (6.9% and 9.0% for the 0.25 mm and 0.5 mm thick gasket, respectively), which was considered acceptable (see Table S1 in the Supporting Information).
Next, we assessed the utility of this novel electrochemical flow reactor by examining its performance in two electrochemical transformations.
In addition, during this experiment, the temperature of the reaction mixture was constantly monitored via a thermocouple at the outlet of the reactor . The temperature remained constant during the entire experiment, which proves that our microreactor dissipates efficiently the generated heat to the environment.
Screening of different parameters (B: Residence Time, C: Gasket Thickness, D: Electrolyte)
Herein, we have described and validated a novel, undivided-cell electrochemical flow reactor. The reactor is modular and can be fabricated with straightforward machining techniques. A unique feature of this reactor is the flexible reactor volume which can be used in a serial (volume ranging from 88 μL/channel up to 704 μL) or parallel mode (i.e. numbering-up). The electrochemical flow reactor was subsequently assessed in two synthetic transformations, which confirms its versatility and scale-up potential. Application of this reactor in other electrochemical transformations is currently pursued in our lab and will be reported in due course.
Financial support was provided by the Dutch Science Foundation (NWO) through a VIDI grant for T.N. (Grant No.14150). Y.C. acknowledges the support from the China Scholarship Council (CSC).
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