Metal‐Free Electrochemical Reduction of Disulfides in an Undivided Cell under Mass Transfer Control

Abstract

Electroorganic synthesis is generally considered to be a green alternative to conventional redox reactions. Electrochemical reductions, however, are less advantageous in terms of sustainability, as sacrificial metal anodes are often employed. Divided cell operation avoids contact of the reduction products with the anode and allows for convenient solvent oxidation, enabling metal free greener electrochemical reductions. However, the ion exchange membranes required for divided cell operation on a commercial scale are not amenable to organic solvents, which hinders their applicability. Herein, we demonstrate that electrochemical reduction of oxidatively sensitive compounds can be carried out in an undivided cell without sacrificial metal anodes by controlling the mass transport to a small surface area electrode. The concept is showcased by an electrochemical method for the reductive cleavage of aryl disulfides. Fine tuning of the electrode surface area and current density has enabled the preparation of a wide variety of thiols without formation of any oxidation side products. This strategy is anticipated to encourage further research on greener, metal free electrochemical reductions.

Scalable Quasi-Divided Cell Operation Using Spinning Cylinder Electrode Technology: Multigram Electrochemical Synthesis of an Axitinib Intermediate

“…In this study, based on the optimal electrode materials found in our previous work on the reductive cleavage of disulfides, a cylinder made of leaded bronze (CuSn 7 Pb 15 ) (94 cm 2 surface area) was used as the spinning working electrode and graphite rods (1/8 in. diameter) as the counter electrode.…”

“…It has previously been shown that electrochemical synthesis of thiol 8 in an undivided cell using a “quasi-divided” cell approach takes place efficiently when a ratio between the surface area of the cathode and the anode of ca. 200:1 is used . The small-scale (3 mL volume reaction) proof-of-concept study provided an 89% isolated yield (90 mg) of 8 after liquid–liquid extraction when the electrolysis was carried out under a current density at the cathode of 26 mA/cm 2 .…”

“…200:1 is used . The small-scale (3 mL volume reaction) proof-of-concept study provided an 89% isolated yield (90 mg) of 8 after liquid–liquid extraction when the electrolysis was carried out under a current density at the cathode of 26 mA/cm 2 . Given that the surface area of the spinning cylinder cathode was 94 cm 2 , such a cathode/anode ratio could be achieved by incorporating five graphite anode rods into the system (5 × 7.9 mm 2 ).…”

“…On the other hand, divided cell setups, particularly on technical or commercial scales, rely on the use of ion exchange membranes such as Nafion, which are not well suited to operate in organic solvents . To solve these issues, we have recently reported an electrochemical method for the reduction of disulfides to thiols in undivided cells that does not require sacrificial electrodes . The method is based on the generation of a mass-transfer barrier between the compounds in solution and the anode surface by simply using an anode with a very small size compared with the cathode.…”

“…Thus, while the disulfide can readily diffuse to the cathode surface and undergo reduction, the diffusion of species in solution to the anode is very slow, preferably oxidizing the solvent instead. This type of electrolysis operation, known as a “quasi-divided” cell, has been useful in the past for the preparation of small amounts of material. , To the best of our knowledge, no scale-up strategies for this type of cell operation have been described.…”