A Historical Perspective

Electrochemistry deals with both chemical transformations that generate electricity, and chemical transformations that are induced by electricity. In the span of two hundred years, it evolved from a few obscure and eccentric laboratory phenomena into a highly sophisticated and comprehensive scientific discipline, with applications that permeate all corners of society. Today, batteries of all sizes—from the delicate hand watch to the powerful Tesla automobile—stem from electrochemistry. Corrosion prevention of metal objects, from a tiny galvanized nail to thousands of miles of underground gas pipelines, is based on fundamental principles of electrochemistry. Powerful sensors such as the glucose meter used by tens of millions everyday are developed from the basic understanding of the correlation between glucose oxidation and the magnitude of its corresponding electrical signal. Scores of commodity chemicals, including aluminum and PVC, are manufactured at an industrial scale every year using electrochemical processes. Beyond practical applications, electrochemistry plays a pivotal role in the search for new materials, more sustainable energy sources, and novel strategies for environment cleanup.

In the last two centuries, organic electrochemistry, the study of electricity induced organic transformations, witnessed significant advances as well: the Kolbe decarboxylative oxidation (1848), the reductive coupling of acrylonitrile which led to industrial synthesis of the feedstock material of nylon production by Monsanto (adiponitrile, 1960), the Shono oxidation (1975), and a diverse set of emerging organic transformations pioneered by Schäfer, Little, Yoshida, Moeller, Wright, Baran, Lin, and many others. Organic electrochemistry transformations are driven primarily by electricity, so can often be performed without the need for harsh conditions and expensive reagents. Indeed, sustainability is a major hallmark of electrochemistry.

Despite the many advantages and impressive achievements, modern organic electrochemistry remains a fringe technique practiced by few in the organic chemistry community. Part of the reason is a lack of practical platform. The impetus of exploring organic electrochemistry is severely hampered by the need for expensive and overly sophisticated potentiostats, as well as the significant amount of space necessary for the cumbersome setups. The situation is further complicated by the lack of commercial supplies, particularly standardized electrodes, for preparative organic chemists. IKA’s compact, easy to use, versatile, cost effective, and award winning ElectraSyn 2.0—as well as its standardized electrodes and other accessories—was designed to address these issues. Together, we will usher a new era of organic electrochemistry!

Shono Oxidation

So what happens in an organic electrochemistry reaction? Shono oxidation is one of the classic organic electrochemistry reactions wherein an N-acylamine is oxidized to form an iminium ion which can then be captured by various nucleophiles. For example, Shono oxidation of N-Boc-pyrrolidine in methanol entails the anode extraction of two electrons from the substrate, resulting in the formation of acyliminium ion and a proton. The two electrons travel from the anode to the cathode where they are retrieved by two molecules of methanol to form a molecular hydrogen and two methoxide ions. The iminium ion is sequestered by methoxide to form the final α-oxidation product. An essential facilitator in this process is the electrolyte, typically an organic salt such as Et4NBF4. This electrolyte facilitates movement of the newly formed ionic species in a productive manner and helps to maintain an overall charge distribution of the reaction mixture such that the electrons can move freely from the anode to the cathode. Needless to say, the anode and the cathode reaction go hand-in-hand: the amount of electrons extracted from the anodic oxidation must equal that of the electrons consumed in the cathodic reduction. Problems with either one of the two half reactions will affect the flow of electrons and result in a sluggish overall process.

Divided vs. Undivided Cells

In an undivided electrochemical cell, the cathode and anode are housed in the same chamber. This setup is easy to carry out, as no elaborate glassware/reactor is needed. In addition, the distance between the two electrodes can be easily adjusted, and ionic species can move freely between the electrodes. An example of an electrochemical reaction in a simple undivided cell is water electrolysis in a regular cup with two pencil leads as electrodes. This is something that can be done outside the confines of a laboratory environment. IKA’s supply of standardized vials, electrodes, and their easy assembly makes it extremely convenient for a chemist to quickly evaluate effect of different electrodes on a specific reaction.

In a divided electrochemical cell, the cathode and anode are kept in different chambers, separated by an ion-permeable membrane or salt bridge. This, of course, requires that special membrane or salt bridge and a reaction vessel of complicated design. Another consideration when using a divided cell is that the resistance is typically high due to the separation of electrodes, which may lead to a slower reaction. However, a divided cell allows the possibility of maintaining different chemical environments around the two electrodes, thereby bringing out fine-tuned reactivity inaccessible via an undivided cell. In the case of water electrolysis, the divided cell furnishes hydrogen and oxygen gases in the cathode and anode chambers, respectively. This makes it possible to deliver hydrogen and oxygen as pure products in the divided cell, as opposed to a mixture of hydrogen and oxygen in an undivided cell.

Constant Current vs. Constant Voltage

An electrochemical reaction can be executed at a constant cell current (galvanostatic) or a constant voltage (potentiostatic).

In a constant current reaction, it is easy to calculate the total charge consumption. The disadvantage of the constant current reaction is that the voltage profile of the reaction is often overlooked. The potential that the reaction starts at and the way it changes throughout the course of the reaction are factors critical to the outcome of the reaction. As the redox active species deplete in the course of a constant current reaction, the potential increases. If unattended, this can lead to undesired redox processes and become detrimental to the reaction. If the reaction is executed with the total amount of charge (e.g., 2 Faradays per mole), it is possible for the potential profile to stay within an acceptable range in the course of the reaction. However, if a reaction is run continuously (e.g., for 16 hours), it is especially important in this case to pay attention to the potential and make sure it stays within an acceptable range.

In a constant voltage reaction, the reaction is typically executed with a constant cell voltage which is set by the redox potential of the intended transformation. If there is no prior knowledge about the redox system, cyclic voltammetry studies are often required to set a potential value for the reaction. Constant voltage reactions are less prone to runaway side reactions. The magnitude of the current flow depends on the overall resistance of an electrochemical cell—a high resistance cell will lead to low current and a slow reaction. Ensuring the current and the reaction rate stay within an acceptable range becomes a point of interest for constant voltage reactions.

Overall, the potential range of a constant current reaction must be carefully monitored and controlled to avoid unintended redox processes that may be detrimental to the reaction. Similarly, the current of a constant voltage reaction must remain at a sufficient level to achieve an acceptable rate of reaction. In both cases, the cell resistance can be adjusted, via electrolyte concentration, solvent, cell configuration, electrode surface area, etc., to achieve the control of voltage or current respectively.

Mediated Electrolysis

Sometimes a mediator is used in electrolysis. The mediator is activated on the surface of electrodes under mild condition and then reacts with the redox substrate to initiate the transformation of interest. Upon activation of the substrate, the mediator regenerates itself and participates in the next cycle of redox activation. This overall process is catalytic and enables electrochemical processes that may otherwise require harsh conditions. This is also called indirect electrolysis, as the substrate electrolysis is achieved indirectly via the mediator.

For example, anode oxidation of unactivated methylenes and methines requires high potentials, often above 3 V vs. saturated calomel electrode (SCE). Many organic molecules cannot sustain such an oxidative environment and direct electrochemical oxidation of unactivated methylenes and methines is not feasible. Quinuclidine is oxidized at a much lower potential (~ 1 V) to form a relatively stable radical cation; this radical cation abstracts a hydrogen atom from a methylene or methine to initiate the substrate radical formation and subsequent oxidation steps. In this case, Quinuclidine acts as the mediator of methylene and methine oxidation (Baran, et al., J. Am. Chem. Soc. 2017, 139, 7448).

Aside from quinuclidine and other bicyclic bridgehead amines, common electrochemical oxidation mediators also include triarylamines, TEMPO, halide ions, iodoarenes, O-aminophenols, and N-hydroxyphthalimides.

Similarly, reduction mediators are activated by cathodic reduction. The resulting intermediates act as subsequent reductants to effect the intended reduction. For example, nickel(II) salen has been used as a reduction mediator for intramolecular olefin–ketone reductive couplings.

For reviews on this topic, see
(1) Francke, R.; Little, R. D. Chem. Soc. Rev. 2014, 43, 2492–2521.
(2) Chiba, K.; Okada, Y. Electron Transfer-Catalyzed Reactions. In Organic Electrochemistry, Revised and Expanded; Hammerich, O.; Speiser, B.; CRC Press: Boca Raton, FL, 2016.
(3) Sauer, G.S.; Lin, S. ACS Catal. 2018, 8, 5175-5187.

Redox Potentials

Organic functional groups (Nicewicz, et al., Synlett. 2016, 27, 214):

Potential window of some of the commonly used organic solvent / electrolyte systems (V vs. SCE, with Pt working electrode): MeCN / LiClO4 –3.0 to +2.5 V, MeCN / Et4NBF4 –1.8 to +3.2 V, DMF / Bu4NClO4 –2.8 to +1.6 V, DMSO / LiClO4 –3.8 to +1.3 V, MeOH / LiClO4 –1.0 to +1.3 V, DCM / Bu4NClO4 –1.7 to +1.8 V (Fuchigami, T.; Atobe,; Inagi, S. Fundamentals and Applications of Organic Electrochemistry: Synthesis, Meterials and Devices, John Wiley & Sons, Oxford, 2015).

Useful References

1. Reviews:
(a) Yan, M.; Kawamata, Y.; Baran, P. Chem. Rev. 2017, 117, 13230–13319.
(b) Sperry, J. B.; Wright, D. L. Chem. Soc. Rev. 2006, 35, 605–621.
(c) Moeller, K.D. Tetrahedron 2000, 56, 9527–9554.
(d) Yoshida. J.; Kataoka K.; Horcajada R.; Nagaki, A. Chem. Rev. 2008, 108, 2265–2299.
(e) Francke, R.; Little, R. D. Chem. Soc. Rev. 2014, 43, 2492–2521.
(f) An overview of recent synthetic organic electrochemistry (courtesy of Dr. Yu Kawamata, Scripps Research): https://t.co/cLutBb7AZH
(g) Phil’s 2017 Fall ACS Keynote Address: https://www.bing.com/videos/search?q=baran+keynote&view=detail&mid=7599E38FEADACB2430417599E38FEADACB243041&FORM=VIRE

2. Books:
(a) Fuchigami, T.; Atobe,; Inagi, S. Fundamentals and Applications of Organic Electrochemistry: Synthesis, Meterials and Devices, John Wiley & Sons, Oxford, 2015.
(b) Hammerich, O.; Speiser, B. Organic Electrochemistry, Revised and Expanded, CRC Press: Boca Raton, FL, 2016.
(c) Scott, K. Sustainable and Green Electrochemical Science & Technology; John Wiley & Sons: Oxford, 2017.

3. Baran group meeting slides:
(a) Kawamata 2016: https://baranlab.org/wp-content/uploads/2018/08/Group-Meeting-61210-ver4.pdf
(b) Rosen 2014: http://www.scripps.edu/baran/images/grpmtgpdf/Rosen_2014.pdf
(c) Ambhaikar 2005: http://www.scripps.edu/baran/images/grpmtgpdf/Ambhaikar_Dec_05.pdf