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Electrochemistry For All

Phil Baran and co-workers Ming Yan and Yu Kawamata at Scripps have published an overview of what they feel is needed in synthetic organic electrochemistry, and I have to applaud them for it. The whole area has a lot of potential, but the current state of the field is messy. (Sorry for that sentence; I couldn’t resist. OK, sorry for that one, too. In my defense, the Yan/Kawamata/Baran article avails itself of plenty of easy targets in the same way!). In 2015, electrochemistry was one of the techniques nominated in the comments to this post as containing the largest amount of sheer voodoo, and I’ve also mentioned it in the “surely there must be something else” category. In 2012, I had this to say:

I definitely don’t think that the technique is useless, but it surely doesn’t get used much. One problem is that there are so many different conditions – solvents, electrolytes, electrode materials, voltage/current regimens. If you’ve never done the stuff before, it’s hard to know where to start. And that leads to the next problem, which is that so much of the equipment in the field has been home-made. That makes the activation barrier to trying it yourself that much higher: do you want to do this reaction enough to want to build your own apparatus and troubleshoot it? Or do you have something else to do? If someone sold a standard electrochemistry kit (controller box to run different conditions, set of different electrode materials, etc.), that would free some people up to find out what it could do for them, rather than wondering if they’ve built a decent setup.

It took the Baran group a while to get going on that request, but these are exactly the problems addressed in this paper (mainly because they’re exactly the problems that anyone who’s ever done any electrochemistry has quickly come to realize!) It’s a call for reproducible conditions, which are best arrived at by standardized, modular devices that can run at different scales, including analytical mode, and have interfaces that makes sense to synthetic organic chemists. No such electrochemistry instrument has ever existed, to the best of my knowledge. As long as you have to build your own homebrew rig to do anything useful, very few people will try these reactions at all, and as long as the field is full of homebrew rigs, very few people will be able to reproduce what you do manage to accomplish. The paper mentions just this sort of problem:

In our own experience with electrochemical CH oxidation reactions, this process is prohibitively challenging with added factors such as electrode, electrolyte, current, potential, and resistance all playing crucial roles in the reaction. We have exercised extra caution to ensure the uniformity of all conceivable variables including the size of electrodes while crafting our “homemade” cells; detailed experimental protocols were furnished in the supporting information. However, we were baffled by feedback from industrial collaborators that, despite having adhered closely to our instructions, they were unable to obtain products in similar yields. After several rigorous troubleshooting sessions, we realized that it was the distance between electrodes that triggered the vexing problems

There are, of course, a number of people working on electrochemical methods, and they may or may not be pleased by this call to action. The idea is not to minimize the contributions that people have made over the years – the article itself has a variety of references to very interesting-looking reactions that have been developed by a whole list of other groups. But looking at these transformations, you have to wonder why such a versatile technology hasn’t been picked up more – surely people are interested in C-C bond formation, amination, C-H bond oxidations, and so on? It’s because of just those problems detailed above. The barriers to entry are too high, and the chances of wasted time and effort are too worrisome. And even if you find something, no one else will run the reaction, because they don’t have the equipment, either. So make sure everyone can get the same equipment, and things might just start to change.

And that brings us to this device, introduced at the recent ACS meeting in DC (OK, OK). It’s a collaboration between the Baran group and IKA. It’s scheduled to be available by the end of the year, and it seems that units have already been sent out for evaluation to some of the groups who are working in the electrochemical area. IKA also has an electrochemical flow apparatus for scaleup, and I’ll be most interested to see how all these work together. It’ll presumably be a year or two before we all start seeing results from the “ElectraSyn 2.0”, but here’s hoping that it opens up some new techniques for those of us who’d rather not rummage around looking for the soldering iron.

Update: see the Supporting Information for this paper for an example of what it’s like to build your own electrochemical apparatus. The paper itself, on CH oxidation, is an excellent illustration of why we should care. This new paper on amination, also very interesting, has a look at the ElectraSyn 2.0 in action in its Supporting Information.

Update 2: see this paper for another proposal for a standardized electrochemical cell.

44 comments on “Electrochemistry For All”

  1. David says:

    Boy this would have made highschool labs *much* simpler.

  2. anonymous says:

    Electrochemistry definitely needs this – and Baran’s name will ensure it gets the attention it deserves.
    Pity he couldn’t have cited some of the work from the Brown group at Southampton eg. http://pubs.acs.org/doi/ipdf/10.1021/acs.oprd.5b00260, but I guess that also highlights commercially available kit for flow electrochemistry which would compete with the IKA interest

    1. Derek Lowe says:

      Just added a link to the post – thanks!

    2. Kyle MacDonald says:

      While we’re on the subject of Southampton, there’s also lots of good stuff happening on the theory side of electrochemistry in Giles Richardson’s group in the mathematics department there. My undergraduate thesis built on some stuff they did. It’s basically the Fourier transform of black magic.

  3. Electrochemist says:

    This smacks of the “not invented here” syndrome. There have been synthetic scale potentiostats on the market for decades, and there is at least one billion dollar industry built around electrosynthesis (e.g., the chloralkali industry).

    In the US, Electrochemistry is generally taught as a discipline of Analytical Chemistry, an area that many of the schools producing large numbers of PhDs in Organic Chemistry do not recognize as a valid discipline.

    The idea that someone would make the important “discovery” that the spacing between the anode and cathode is a critical experimental variable that must be controlled sounds to an electrochemist like the statement “we discovered this really interesting idea that temperature effects reaction rate” would sound to an organic chemist!

    1. anoneemous says:

      This smacks of “Boohoo, I know so much more about something than someone else so that person shouldn’t be capable of innovating in my field.”

      All of the facts you say are surely correct, but your conclusions and attitude probably need adjusting. The point of Baran’s work and this device he’s peddling isn’t that they “discovered” anything about electrochemistry. It’s that they’ve been working with engineers at a manufacturing company to develop a device that they hope will be handy for electrochemistry novices to dip their toes in the waters and maybe see some meaningful results. If these things work out and every other hood in academia and both medchem and process chem in the pharmaceutical industry is trying electrochemistry, wouldn’t you see that as a positive thing for your field? That’s really the point here: just as Apple brought mobile computing to novices and opened up brand new markets for everyone selling smartphones, such a push for modularity and standardization might bring electrochemistry to chemists who never would have considered it before.

      But if you ask me, there’s a significant possibility this product will fade into obscurity just like where electrochemistry currently stands in the eyes of synthetic chemists (at least in pharma and academic settings, I know it has powerful uses in other chemical production). If all the electrodes, electrolytes, and whatever other materials you need are not easily available, durable, and swappable then this thing is dead. If throughput for screening is too slow, then this thing will have problems.

      1. anon electrochemist says:

        His point is that these “innovations in the field” are so obvious to someone trained in the art that the organic folk clearly never bothered asking anyone how to do it right and come off as a bunch of pot-boilers.

        Electrons are already commercially available in high purity. I can sell anyone here a potentiostat for less than $1k, along with the appropriate stock glassware, electrolytes, electrodes etc. They’ve been around for decades. Standardizing equipment to improve accessibility is solving the wrong problem. The trouble with electrochem is not a matter of reproducibly handling and adding exotic reagents to your flask.

        If I gave the organic community a “standard cell”, they would not know what knobs to spin in order to troubleshoot any problems they faced. Quickly falling back to Blindly Screening Variables is not productive. I worry about my field being further tinged with the lingering labels of irreproducibility and voodoo now openly slung. The requisite training in physical, analytical, and surface chemistry to read appropriate literature and ask the right questions is simply not available. Derek phrased it best: There is no useful textbook titled “Thermodynamics: A Hand-Waving Approach”. I still have to live here once the Rule-Of-Five’ers have published their Nature papers and moved on.

        1. Electrochemist says:

          Amen, brother.

        2. anoneemous says:

          I totally agree that people not knowing HOW to do electrochemistry will not be helped much by buying a fancy doohicky, but I think standardization is a small step. I also agree the bigger problem is that knowledge of how to do electrochemistry is scarce, but maybe you’d be willing to write a review or a handbook titled “Electrochemistry for Dummies”? It could be a practical guide for synthetic chemists otherwise clueless about electrochemistry. Baran would totally contribute practical requirements if you asked him. Maybe such a thing already exists. If so, could you point me in the right direction? I would totally read this.

          1. anoneemous says:

            Jeez, I wrote “totally” a lot. Sorry.

          2. Electrochemist says:

            Electrochemistry for Chemists 2nd Edition
            by Donald T. Sawyer (Author), Andrzej Sobkowiak (Author), Julian L. Roberts (Author)

            https://www.amazon.com/Electrochemistry-Chemists-Donald-T-Sawyer/dp/0471594687

          3. anon electrochemist says:

            You’ll want “Electrochemistry in Organic Synthesis” by Volke

            Abstract
            This book has been written as an introduction to the electro synthesis of organic compounds, in particular for organic chemists. Both authors assume that the knowledge of electro chemistry of these specialists is rather poor and is usually based only on the remnants of the teaching in the courses on physical and analytical chemistry during their university stud ies. Even with Czech chemists one cannot expect – as it was in the past – the experience obtained in the courses on polaro graphy. This is the reason why it was deemed necessary to write an introductory text to the electro synthesis of organics both as regards the theoretical and the methodological point of view, i. e. the fundamentals, the experimental setup, the application of various working and reference electrodes, the shape and con struction of electrolysis cells, the use of suitable pro tic and aprotic solvents, the experience obtained with various sup porting electrolytes, the separation and isolation of products, as well as the use of inert gases which prevent the interaction of intermediates and of final products with, for example, oxygen or traces of water. – The second part of the book contains a systematic description of preparative organic electrochemical processes, the interpretation of their mechanisms and several prescriptions for synthesizing characteristical groups of com pounds. As a whole the book is not written in an exhaustive way

        3. Hap says:

          1) I don’t remember learning anything about electrochemistry in college thermo (let alone mass and electron transfer and associated distance dependences), while we learned about reaction temperature dependence in high school. One of these pieces of knowledge is different than the other, I think.

          2) If other people can’t use your technique to do useful things predictably, then either you don’t know it well enough (the “voodoo” contention) or can’t explain it well enough. If the barrier for entry for use of a technique is a PhD in it and 20 years working with it, it isn’t going to be very useful. The knowledge of a technique doesn’t have to fit on a notecard, but people with reasonable skill in chemistry should be able to learn how to use it reproducibly in finite time. If no one can, then maybe the theoretical users aren’t the problem.

          1. Electrochemist says:

            Maybe you should have taken an analytical chemistry course in college.

          2. anon electrochemist says:

            Hap, I’ve made no claims regarding the utility of electrochemistry towards organic synthesis, but would prefer not to have the scientific quality of the field judged on these merits by inexperienced users. I of course agree that thermo and electrochem are not the same. Given that the standard curriculum includes only thermo, the electrochemistry should be trickier!

            If the biologists were proposing “Retrosynthesis For Dummies” as a way of getting reliable research results faster, you would see some teeth grinding over here. You can hear the howling every time theres a paper on some 3D printed reactor robot simplifying synthesis. But, we’re all in this together. My colleagues and I are happy to collaborate or consult. Buy your local specialist a coffee, stop by the other end of the hall at an ACS meeting. Or hell, get an electrochemist postdoc. You will have an experienced hand to navigate this admittedly arcane field, and I won’t have a wave of poorly performed literature dumped on my niche.

          3. tangent says:

            “Maybe you should have taken an analytical chemistry course in college.”

            Well okay, but maybe the electrochemistry field would get better results if people didn’t have to get tipped off to the fact that there are useful synthesis techniques hiding in the analytical course?

            Dude you’ve got an opportunity. You’ve got knowledge that people are missing, that’s great to hear, so why not give it to them. Either take the opportunity or face watching other people do it, maybe not as well as you could have, but also knowing that “what I could have done” stories get a real short leash.

          4. Electrochemist says:

            Those whose formal educations consists solely of experiences at schools without a decent basketball team will invariably have significant gaps in their knowledge. Note that I am not claiming causality here, merely robust correlation.

            The onus lies on those with the gaps in their knowledge to engage *constructively* with their colleagues in other fields, not endlessly spew statements about the “lack of reproducibility” of work in areas in which they have little experience or understanding.

            I remember hearing Allen Bard refer to this as “unbridled hubris” of certain colleagues once. Spot on, Al.

          5. Hap says:

            Um, I’m pretty sure that I didn’t have worry about the money my school wasn’t spending on an analytical chemistry class ending up in athletics (I don’t think a 6-3 record in D3 football would have lubed up the alumni donations). I’m also wondering how much time would actually get spent in an analytical chem class on electrochemistry (considering all of the methods of analysis and instrumentation, it’s hard to imagine having more than two or three sessions on electrochem unless it’s a multi course sequence).

            It’s hard to know what you don’t know in a new field if there’s a high barrier to entry (enzyme-mediated synthesis)?

    2. Humulonimbus says:

      Have not read the article yet, but Derek’s quote reads “we realized,” not “we discovered.”

    3. Chris Phoenix says:

      Note that no one, in two electrochemistry groups, trying to figure out why results weren’t replicable, thought to ask “How far apart are your electrodes”?

      Even though they were building physical equipment!

      It may be obvious to you. It may be obvious in hindsight. It is not obvious in general.

      I once sat through a presentation at a complex systems conference, where they took half an hour to describe how they had discovered some interesting counterintuitive behavior in their (software) simulation. To me it was embarrassingly obvious that it was just a complicated way of implementing the modulo function. But a dozen smart people worked on it for months and brought it to a conference.

      Maybe we need more communication between groups, and more communication with people who are polymathic. Go ahead – find a group that’s smart, working on an interesting problem, and doesn’t know what you know about electrochemistry, and schedule a lunch with them.

  4. Rhenium says:

    Oh great…

    First we’ll queue up the “Baran didn’t do anything novel” posts, swiftly followed by the Baran groupies claiming “None of you understand the Great Leader”.

    If I didn’t know better I’d say that Derek posted these things for the additional controversy and page hits…

    1. IngSoc says:

      MacMillania has always been at war with Baranasia

  5. Paul D. says:

    Thank you for this update on current events.

  6. Humulonimbus says:

    “Given the aforementioned rich history and useful reactivity enabled by electrochemistry, why is it rarely employed by modern day chemists? We hypothesize that the answer is due to a lack of engineering savvy directed in this area rather than a lack of potential interest. For example, NMR spectroscopy would be nothing more than a fringe technique used by only a handful of physicists if not for engineering advances in equipment technology. Consider the fate of computer sciences if each user were required to construct a “Turing machine” from scratch. In a similar vein, aspiring electroorganic chemists face such a quandary. To be sure, all the enabling technologies behind electrosynthesis had matured by the second half of the 20th century (Figure 1B).”

    The authors pretty clearly state that they haven’t invented anything fundamental, and that the major roadblocks to the application of electrochemistry in organic synthesis are engineering challenges. I think the hypothesis is reasonable and will be either validated or invalidated when this instrument is unveiled and put to the test in synthetic chemistry laboratories.

    I don’t think the first iteration is going to make high-throughput experimentation feasible. So what? There are plenty of chemists who still get by the old-fashioned way, and as long as enough of them get started to expand interest, there will be follow-on instruments.

  7. Another Electrochemist says:

    I’m a practicing electrochemist, and I find the field fascinating. It truly is multi-disciplinary.

    In my estimation, a lot of the problems (e.g. with reproducibility) are due to considering the electrodes as blobs of metal that complete the circuit so the electrons can do their thing. For most situations, nothing could be further from the truth. Electrochemistry happens at the interface, and you can get into the material science aspects of things too – what does the surface of a metal look like? How does your preparation and pre-treatment affect that (talk about black magic stuff!).

    Then there’s transport effects (which factors into the engineering challenges) and as already pointed out, the instrumentation and cell design factors too. A fair amount of what goes into these considerations is not taught in chemistry curricula – chemical engineering, electrical engineering, and materials science come to mind as disciplines having more appropriate courses. So I could understand a certain resistance (yes, pun intended) to try electrochemical routes.

    1. Mark Thorson says:

      That’s certainly true. But if this machine is designed right, maybe the whole thing will be automated at a level never achieved before. Temperature, current density, pulse rate, duty cycle, etc. might all be controlled by the computer. To reproduce someone else’s work, just download his configuration file from the net into your machine.

  8. Cato says:

    I had to do some Nordic electrochemistry in grad school to oxidize some furans, and lacking funds, ended up whittling down graphite pencils for my electrodes and clamped them in a three necked flask with a battery I found somewhere. These might have not been glassy carbon but it worked! A cheap standardized system would be great to avoid this!

  9. Christophe Verlinde says:

    The first author of the paper, Ming Yan, may be a bit miffed with Derek’s attribution “Phil Baran and co-worker Yu Kawamata at Scripps have published …”. Derek, please correct.

    1. Derek Lowe says:

      Jeez, he should be. Don’t know how I missed that – probably because I was looking at it on my phone screen. Corrected immediately.

  10. David Millhouse says:

    Using electricity to power electrodes will never be as efficient as using it to power LEDs for photochemistry. Photoredox: 1 Electrochem: 0

    1. Dorky doofus says:

      That’s laughable. Try powering your car with solar panels on the roof.

      Electrochemistry is the most direct way to do electron transfer. The current density you can achieve makes it far easier to scale as well.

      1. Iced says:

        Bro my Honda passat stick shift runs on gas who cares

    2. Bagger Vance says:

      See, this is what surprises me, that what seem relatively more difficult and uncontrollable techniques have caught fire, while this one (which appears easier from several angles) has not. I just thought i was missing something more fundamental about the comparisons.

    3. Fauxtoredox says:

      Ya what could be better than using complicated iridium complexes in 2 mol% loadings? I love it when these rarest-crustal-element catalysts are completely destroyed during the course of the reaction and not able to be recycled. Good technology.

      1. milkshaken says:

        Ir is unfortunate but Ru is fairly affordable, it costs only slightly more than Ag. I used to buy 250g bottles of RuCl3.3H2O from Pressure Chemicals at about 2-3USD/g

        Blue LEDs are not so bad since you don’t need eye protection and the coling issues are less dramatic than with UV photoreactors. But you still need a dedicated photo-rig on scale so the dark Ni, Fe radical decarboxylation chemistry developed by Baran group definitely has an edge over its photocatalyzed competitors

        1. Design Monkey says:

          Eh, yeah, ruthenium is cheap, iridium, though, not so. And when your catalyst organic ligands start to cost (way) more than precious metal itself, then it’s a trouble in cash department.

    4. Dcm says:

      Screen the electrode library doesn’t have quite the same ring to it

  11. TSRI alumni and Nature Coauthor says:

    Great for Phil. Knowing TSRI, the first authors had to endure several years of daily harrasment and they will be fired in 6 months. Pfizer will assume control of publication results.

    1. current TSRI student says:

      This couldn’t be further from the truth! Phil treats his students and post-docs incredibly well. I’m not even in the Baran lab, and seeing the mentorship and positive reinforcement makes me envious

      1. milkshaken says:

        I have lived through some very nasty stuff at Scripps FL medicinal chemistry, mostly related to power infighting and money issues, but I noticed the great independence of different research groups. If you have secure funding you can be fully autonomous within the bureaucratic whale of Scripps.

        Also, I never heard of anyone in the group getting screwed by Phil Baran – like you hear sometimes about other research groups at TSRI

  12. Don't taze me bro says:

    Perhaps IKA could make a video where scantily clad ladies taze Baran to promote e chem

  13. Anonymous says:

    Humulonimbus pointed out a few examples of early tech that needed a while to become more accepted. I was going to mention HPLC and microwave synthesis.

    Numerous components of early HPLCs had reliability issues. One company’s “10 micron silica” could give a completely different separation than another company’s batches. (I don’t just mean resolution. I had elution sequences invert of different silicas.) Just getting a stable baseline could take up most of your day.

    The earliest earliest papers on microwave synthesis that I recall described the use of modified kitchen microwave ovens. One was a flow system: two holes drilled in the oven wall, a coil of flexible tubing and a peristaltic pump to circulate the solution.

    As a grad student, I needed to perform a transformation that proved recalcitrant to MANY conventional methods. I cobbled together some parts to try some electrosynthesis. It also failed but the (very famous) PI was LESS than appreciative of the effort. (I learned a fair bit of electro chemistry, but the non-chemistry lesson was the bitterest pill to swallow.)
    (I also spent many days sleeping at the lab to nurse my reactions; no sleeping bag, just my winter coat as a blanket.)

    Anybody remember the “old” Electrosynthesis Company? They go back to the 80s and maybe even earlier. They are still around. What about Pine Research? I thought the Baran group was working with them?

    I welcome improved accessibility of electrochem / electrosynthesis equipment. There are already MANY “conventional” organic synthesis claims that simply do not work as published and waste a lot of our time. What’s another reproducibility problem here and there? Use your common, chemical, and electrochemical sense to decide if something is worth trying.

    Once you have the equipment in your lab, you can work on Cold Fusion while some of those slow, conventional reactions are cooking in the hood.

  14. Andrew Lund says:

    I’m endlessly fascinated (and equally appalled at my lack of understanding) by industrial electrochem processes. Here’s a link to a site with a lot of info:

    http://knowledge.electrochem.org/encycl/art-o01-org-ind.htm

  15. Design Monkey says:

    Accidentally got in my hands ancient (2003) IKA catalog. And, lo and behold, IKA already then had preparative electrochemical thingamabob for sale. Not as cute and sleek as present one and without built-in analytical features, but still. And it did not made any revolutionary change among organic chemists regarding use of electrochemistry.

    The crux of the matter here is not and never was about availability of hardware.

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