Enhancing Performance of Organic Electrosynthesis through Electrolyte Engineering and Mass Transport Control
Authors: Modestino Miguel A , Blanco Daniela Eugenia 
Published: July 2021

Organic electrosynthesis has gained significant interest in pharmaceutical manufacturing over the past decade. This increased interest has been propelled by a proliferation of new green chemical synthesis methods that are highly selective, avoid the use of stoichiometric reducing or oxidizing agents, and reduce the need for downstream separations. Given this recent synthetic advances, reaction engineering approaches start to become important in order to achieve scalable chemical manufacturing processes that operate at high selectivity and high production rates. This presentation will discuss reaction engineering opportunities based on electrolyte design and transport control to enhance the performance of organic electrosynthesis processes. Specifically, I will present our work on understanding and improving the electrohydrodimerization of acrylonitrile (AN) for the production of adiponitrile (ADN) – a model electrochemical processes currently implemented at scale. Although this reaction is the largest and most successful organic electrosynthesis implemented in industry, it faces many challenges owing to its limited energy conversion and selectivity, which are common to reactions of interest in pharmaceutical manufacturing. I will first discuss the role of complex multi-ion electrolyte formulation on the selectivity of this reaction. [1, 2] Specifically, I will discuss the effects that supporting ions play in the electrical double layer (EDL) to control the reactivity of intermediates and direct electrochemical reactions towards desirable reaction pathways. We systematically explored the effects of the size of cations in the electrolyte and show that larger cations enhance selectivity towards ADN by modulating the reactivity of reactants and intermediates in the EDL. Furthermore, we show that intermediate pH regimes (between 7 and 11) are favorable for the production of ADN. Lower pH values enhance the hydrogen evolution reaction (HER) and the hydrogenation of AN, leading to the production of propionitrile (PN). Through the careful formulation of electrolytes, the concentration of reactants, operating current densities, and temperature, ADN selectivities as high as 83% can be achieved at intermediate current densities (- 26 mA cm-2). However, mass transport limitations have proven to be a challenge at high current densities, where the production of propionitrile (PN) dominates.
In the second part of the presentation, I will provide experimental insights on how pulsed potential techniques can be used to mitigate mass transport limitations and effectively control the product distribution in ADN electrosynthesis.[3] Electrochemical pulses are used to balance AN diffusive flux to the electrode and its consumption in the electrical double layer (EDL), helping mitigate mass transport limitations at high current densities. This, together with their effect on the interaction between electroactive species and the reaction surface can help improve reaction selectivity. An improvement of over 250% in relative selectivity between ADN:PN was achieved optimizing pulse duration and amplitude, and a 20% increase in ADN production rate was achieved with respect to DC operation. The experimental data obtained for various pulse durations was then used to train machine learning algorithms which identified an optimal pulse sequence with a demonstrated 30% increase in ADN production with respect to DC operation. This new approach to electrosynthesis research which combines electrochemical design principles, judiciously designed experimental campaigns and machine learning can be used to uncover and optimize new electrosynthetic processes in pharmaceutical manufacturing.
[1] Blanco, D. E., Dookhith, A. Z., & Modestino, M. A. (2019). Enhancing selectivity and efficiency in the electrochemical synthesis of adiponitrile. Reaction Chemistry & Engineering, 4(1), 8-16.
[2] Blanco, D. E., Atwi, R., Sethuraman, S., Lasri, A., Morales, J., Rajput, N. N. and Modestino, M. A. Effect of Electrolyte Cations on Organic Electrosynthesis: The Case of Adiponitrile Electrochemical Production, Journal of The Electrochemical Society, 2020, 167, 155526.
[3] Blanco, D. E., Lee, B., & Modestino, M. A. (2019). Optimizing organic electrosynthesis through controlled voltage dosing and artificial intelligence. Proceedings of the National Academy of Sciences, 116(36), 17683-17689.