Versatile Flow Electrochemical Methodology for the Manufacturing of Pharmaceutically Relevant Sulfoxides and Sulfones from Thioethers
Kevin Simon, Rakeshwar Bandichhor, Mallesh Beesu, Inukonda Surya Manisha, Gabriele Laudadio, C. Oliver Kappe, Srinivas Oruganti, Rajeev Rehani Budhdev, David Cantillo
Abstract
High Resolution Image Download MS PowerPoint Slide An electrochemical method for the selective oxidation of thioethers to sulfoxides or sulfones has been developed. The method is based on the use of an electrolyte comprising safe and inexpensive CaCl 2 in a MeCN/H 2 O solvent system. Apart from enabling the selective synthesis of sulfoxides or sulfones by simply tuning the electrolysis conditions, the procedure has been shown to be amenable to complex structures. Thus, several active ingredients, including pantoprazole, lansoprazole, or dapsone have been synthesized using this electrochemical methodology. An additional advantage of the CaCl 2 /MeCN/H 2 O electrolyte system is that it is homogeneous, enabling processing in a parallel plate flow electrolysis cell, and thus ensuring that the procedure can be scaled up and transferred to commercial settings. Additionally, the electrolysis protocol has also been translated to a spinning cylinder electrode electrochemical reactor, which can also be operated in the flow mode. In this reactor, excellent reaction conversion and selectivity for the challenging electrochemical synthesis of pantoprazole from the corresponding thioether precursor has been demonstrated on a multi-gram scale.