Overview of Recent Scale-Ups in Organic Electrosynthesis (2000–2023)

Abstract

This review summarizes examples of organic electrosynthesis from the peer-reviewed literature from 2000 to 2023 that have been conducted on scales of 20 g or above. A significant portion of these examples were conducted on a ≤100 g scale, while detailed reports of kilogram-scale electrosynthesis remain scarce in the pharmaceutical industry. In addition to the chemical transformation, this review also highlights the type of reactor used and a projected productivity metric as ways to compare the different reports. The selected examples of organic electrosynthesis scale-ups described herein also illustrate the remaining challenges currently preventing the routine use of large-scale electrosynthesis in the pharmaceutical industry.

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

“…Over the past years, there has been a growing trend toward the development of single-pass electrochemical flow processes, as they enable genuinely continuous processing of materials. − Continuous processing, in turn, enables the integration of multistep synthetic routes into a single stream and facilitates the generation and inline consumption of unstable intermediates . We have previously demonstrated that the spinning electrode cell technology can be operated in continuous mode by assembling a cascade of reactors, which would essentially behave as a continuous stirred tank electrochemical reactor cascade (CSTERC) .…”

Diversification of Pharmaceutical Manufacturing Processes: Taking the Plunge into the Non-PGM Catalyst Pool

“…Non-PGM (base metals as well as first-row transition metals) catalysts have been used on large scale in other industries for many years. We can see a parallel between the earlier adoption of electrochemistry in the fine chemical industry (e.g., the Monsanto adiponitrile process, 1965) and the recent exploration of this technology for pharmaceutical processes . We encourage readers in the pharmaceutical development community to look to other industries (e.g., fine chemicals, material science, polymers) for inspiration in developing new applications of non-PGM catalysis.…”

“…We can see a parallel between the earlier adoption of electrochemistry in the fine chemical industry (e.g., the Monsanto adiponitrile process, 1965) and the recent exploration of this technology for pharmaceutical processes. 157 We encourage readers in the pharmaceutical development community to look to other industries (e.g., fine chemicals, material science, polymers) for inspiration in developing new applications of non-PGM catalysis. It is never too late to start, and one never knows what one will find.…”

Electrosynthesis of iminophosphoranes and applications in nickel catalysis

“… 29 Ultimately, safe and scalable methods with broad scope are in high demand. To address these limitations, we wondered whether electrochemistry 30 could be used to convert commercially available P( iii ) ligands to P( v ) iminophosphorane sp 2 - N -ligands ( Scheme 2A ) via an environmentally sustainable and operationally simple and safe process. The potential to access novel iminophosphorane-containing P N ligands from readily available phosphines would quickly expand the diversity of bi- and tridentate ligands in analogy to the classic sp 2 -nitrogen-based bipyridine and terpyridine ligands ( Scheme 2B ), which are gaining popularity in base-metal catalysis.…”