Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

A practical guide to electrosynthesis

Nature Reviews Chemistry volume 6, pages 275–286 (2022)Cite this article

Subjects

Abstract

Organic electrosynthesis is an old and rich discipline. By exploiting the cheapest and greenest source of electrons, electricity itself, electrolysis has been shown to be a powerful method to perform redox reactions under mild, safe and green conditions. The field is in the midst of a renaissance and there is little doubt that it will become one of the classic methods to activate small organic molecules in the very near future. Nevertheless, electrosynthesis can be rather daunting for a beginner. In this Review, we will guide synthetic chemists through their first organic and organometallic electrosyntheses by reviewing the essential aspects of the field and by sharing practical tips. We will also cover the fundamentals of electroanalytical techniques, such as cyclic voltammetry, since they are powerful methods to investigate mechanisms. Finally, these concepts will be examined in practice through three case studies.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: An electrochemical cell used for cyclic voltammetry.
Fig. 2: Principles of cyclic voltammetry.
Fig. 3: Simple electrochemical reaction setup.
Fig. 4: Applications of the Kolbe reaction.
Fig. 5: Experimental cyclic voltammograms and proposed mechanism for the oxidation of (p-FC6H4S)2.
Fig. 6: Proposed reaction pathways after electrochemical oxidation of ruthenocene.

Similar content being viewed by others

References

  1. Faraday, M. Experimental researches in electricity. Philos. Trans. R. Soc. Lond. 122, 125–162 (1832).

    Google Scholar 

  2. Kolbe, H. Untersuchungen über die Elektrolyse organischer Verbindungen. Justus Liebigs Ann. Chem. 69, 257–294 (1849).

    Article  Google Scholar 

  3. Yan, M., Kawamata, Y. & Baran, P. S. Synthetic organic electrochemical methods since 2000: on the verge of a renaissance. Chem. Rev. 117, 13230–13319 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hammerich, O. & Speiser, B. Organic Electrochemistry: Revised and Expanded (CRC Press, 2015).

  5. Bard, A. J. & Faulkner, L. R. Electrochemical Methods: Fundamentals and Applications (Wiley, 2000).

  6. Elgrishi, N. et al. A practical beginner’s guide to cyclic voltammetry. J. Chem. Educ. 95, 197–206 (2018).

    Article  CAS  Google Scholar 

  7. Sawyer, D. T., Sobkowiak, A. & Roberts, J. L. Electrochemistry for Chemists (Wiley, 1995).

  8. Kissinger, P. & Heineman, W. R. Laboratory Techniques in Electroanalytical Chemistry, Revised and Expanded 2nd edn (Taylor & Francis, 1996).

  9. Paddon, C. A., Silvester, D. S., Bhatti, F. L., Donohoe, T. J. & Compton, R. G. Coulometry on the voltammetric timescale: Microdisk potential-step chronoamperometry in aprotic solvents reliably measures the number of electrons transferred in an electrode process simultaneously with the diffusion coefficients of the electroactive spec. Electroanalysis 19, 11–22 (2007).

    Article  CAS  Google Scholar 

  10. Amatore, C. et al. Absolute determination of electron consumption in transient or steady state electrochemical techniques. J. Electroanal. Chem. 288, 45–63 (1990).

    Article  CAS  Google Scholar 

  11. Nicholson, R. S. & Shain, I. Theory of stationary electrode polarography: single scan and cyclic methods applied to reversible, irreversible, and kinetic systems. Anal. Chem. 36, 706–723 (1964).

    Article  CAS  Google Scholar 

  12. Britz, D. & Strutwolf, J. Digital Simulation in Electrochemistry (Springer, 2018).

  13. Leech, M. C., Garcia, A. D., Petti, A., Dobbs, A. P. & Lam, K. Organic electrosynthesis: from academia to industry. React. Chem. Eng. 5, 977–990 (2020).

    Article  CAS  Google Scholar 

  14. Heard, D. M. & Lennox, A. J. J. Electrode materials in modern organic electrochemistry. Angew. Chem. Int. Ed. 59, 18866–18884 (2020).

    Article  CAS  Google Scholar 

  15. Pletcher, D. & Walsh, F. C. Industrial Electrochemistry (Springer, 1993).

  16. Colomer, I., Chamberlain, A. E. R., Haughey, M. B. & Donohoe, T. J. Hexafluoroisopropanol as a highly versatile solvent. Nat. Rev. Chem. 1, 0088 (2017).

    Article  CAS  Google Scholar 

  17. McKee, R. H. & Gerapostolou, B. G. Electrolytic reduction of nitro compounds in concentrated aqueous salt solutions. Trans. Electrochem. Soc. 68, 329 (1935).

    Article  Google Scholar 

  18. McKee, R. H. & Brockman, C. J. A new method for electro-organic reductions. Trans. Electrochem. Soc. 62, 203 (1932).

    Article  Google Scholar 

  19. Eberson, L. & Helgée, B. Studies on electrolytic substitution reactions. IX. Anodic cyanation of aromatic ethers and amines in emulsions with the aid of phase transfer agents. Acta Chem. Scand. B 29, 451–456 (1975).

    Article  Google Scholar 

  20. Eberson, L. & Helgée, B. Studies on eectrolytic substitution reactions. XII. Synthesis of 4-alkoxy-4′-cyanobiphenyls — a class of liquid crystals — via anodic cyanation of 4,4′-dialkoxybiphenyls in emulsion systems. Acta Chem. Scand. B 31, 813–817 (1977).

    Article  CAS  Google Scholar 

  21. Eberson, L. & Helgée, B. Studies on electrolytic substitution reactions. XIII. Anodic acyloxylation of aromatic substrates in emulsion systems with the aid of phase transfer agents. Acta Chem. Scand. B 32, 157–161 (1978).

    Article  Google Scholar 

  22. Teherani, T., Itaya, K. & Bard, A. J. An electrochemical study of solvated electrons in liquid ammonia. Nouv. J. Chim. 2, 481–487 (1978).

    CAS  Google Scholar 

  23. Liu, T. et al. New insights into the effect of pH on the mechanism of ofloxacin electrochemical detection in aqueous solution. Phys. Chem. Chem. Phys. 21, 16282–16287 (2019).

    Article  CAS  PubMed  Google Scholar 

  24. Izutsu, K. Electrochemistry in Nonaqueous Solutions (Wiley, 2011).

  25. Kathiresan, M. & Velayutham, D. Ionic liquids as an electrolyte for the electro synthesis of organic compounds. Chem. Commun. 51, 17499–17516 (2015).

    Article  CAS  Google Scholar 

  26. Torriero, A. A. J. Electrochemistry in Ionic Liquids (Springer, 2015).

  27. Comminges, C., Barhdadi, R., Laurent, M. & Troupel, M. Determination of viscosity, ionic conductivity, and diffusion coefficients in some binary systems: ionic liquids + molecular solvents. J. Chem. Eng. Data 51, 680–685 (2006).

    Article  CAS  Google Scholar 

  28. Schäfer, H. J. Recent contributions of Kolbe electrolysis to organic synthesis. Top. Curr. Chem. 152, 91–151 (1990).

    Article  Google Scholar 

  29. Tanaka, H., Kuroboshi, M. & Torii, S. in Organic Electrochemistry 5th edn 1267–1307 (CRC Press, 2015).

  30. Moeller, K. D. Synthetic applications of anodic electrochemistry. Tetrahedron 56, 9527–9554 (2000).

    Article  CAS  Google Scholar 

  31. Schäfer, H. J. Recent synthetic applications of the Kolbe electrolysis. Chem. Phys. Lipids 24, 321–333 (1979).

    Article  Google Scholar 

  32. Wiebe, A. et al. Electrifying organic synthesis. Angew. Chem. Int. Ed. 57, 5594–5619 (2018).

    Article  CAS  Google Scholar 

  33. Hayrapetyan, D., Shkepu, V., Seilkhanov, O. T., Zhanabil, Z. & Lam, K. Electrochemical synthesis of phthalides via anodic activation of aromatic carboxylic acids. Chem. Commun. 53, 8451–8454 (2017).

    Article  CAS  Google Scholar 

  34. Dickinson, T. & Wynne-Jones, W. F. K. Mechanism of Kolbe’s electrosynthesis. Part 3. — Theoretical discussion. Trans. Faraday Soc. 58, 400–404 (1962).

    Article  CAS  Google Scholar 

  35. Schäfer, H. J. Anodic and cathodic CC-bond formation. Angew. Chem. Int. Ed. Engl. 20, 911–934 (1981).

    Article  Google Scholar 

  36. Nuding, G., Vögtle, F., Danielmeier, K. & Steckhan, E. Rodlike molecules by Kolbe electrolysis. Synthesis 1996, 71–76 (1996).

    Article  Google Scholar 

  37. Seebach, D. & Renaud, P. Chirale Synthesebausteine durch Kolbe-Elektrolyse enantiomerenreiner β-Hydroxy-carbonsäurederivate. (R)- und (S)-Methyl-sowie (R)-Trifluormethyl-γ-butyrolactone und -δ-valerolactone. Helv. Chim. Acta 68, 2342–2349 (1985).

    Article  CAS  Google Scholar 

  38. Stang, C. & Harnisch, F. The dilemma of supporting electrolytes for electroorganic synthesis: a case study on Kolbe electrolysis. ChemSusChem 9, 50–60 (2016).

    Article  CAS  PubMed  Google Scholar 

  39. Matzeit, A. et al. Radical tandem cyclizations by anodic decarboxylation of carboxylic acids. Synthesis 11, 1432–1444 (1995).

    Article  Google Scholar 

  40. Bestmann, H. J. et al. Pheromone, 57. Synthese Methylen-unterbrochener Lepidopteren-Polyenpheromone und Strukturanaloger. Acetylensynthese, Wittig-Reaktion und Kolbe-Elektrolyse. Liebigs Ann. Chem. 1987, 417–422 (1987).

    Article  Google Scholar 

  41. Rossi, R., Carpita, A. & Chini, M. Synthesis of the two enantiomers of the sex pheromone of Diabrotica Undecimpunct at a Howardi and of chiral precursors of other pheromones starting from enantiomerically pure methyl hydrogen (R)-3-methylglutarate. Tetrahedron 41, 627–633 (1985).

    Article  CAS  Google Scholar 

  42. Jensen-Korte, U. & Schäfer, H. -J. Pheromone, 7. Kolbe-Synthese von 29-tert-Butyldimethylsilyloxy-3,11-dimethyl-1-nonacosen, einer Schlüsselverbindung zur Darstellung eines optisch aktiven Sexuallockstoffes der Deutschen Hausschabe. Liebigs Ann. Chem. 1982, 1532–1542 (1982).

    Article  Google Scholar 

  43. Seebach, D. Preparation of enantiomerically pure compounds employing anodic oxidations of carboxylic acids – A late review of research done in the 1980ies. Helv. Chim. Acta 102, e1900072 (2019).

    Article  Google Scholar 

  44. Brecht-forster, A., Fitremann, J. & Renaud, P. Synthesis of (±)-nephromopsinic, (−)-phaseolinic, and (−)-dihydropertusaric acids. Helv. Chim. Acta 85, 3965–3974 (2002).

    Article  CAS  Google Scholar 

  45. Becking, L. & Schäfer, H. J. Pyrrolidines by intramolecular addition of Kolbe radicals generated from β-allylaminoalkanoates. Tetrahedron Lett. 29, 2797–2800 (1988).

    Article  CAS  Google Scholar 

  46. Lebreux, F., Buzzo, F. & Marko, I. E. Studies in the oxidation of carboxylic acids: new twists for an old reaction. Synthesis of various cyclic systems and substituted orthoesters. ECS Trans. 13, 1 (2008).

    Article  CAS  Google Scholar 

  47. Lebreux, F., Buzzo, F. & Markó, I. E. Synthesis of five- and six-membered-ring compounds by environmentally friendly radical cyclizations using Kolbe electrolysis. Synlett 2008, 2815–2820 (2008).

    Article  Google Scholar 

  48. Hofer, H. & Moest, M. Ueber die Bildung von Alkoholen bei der Elektrolyse fettsaurer Salze. Justus Liebigs Ann. Chem. 323, 284–323 (1902).

    Article  CAS  Google Scholar 

  49. Yoshikawa, M., Wang, H. K., Tosirisuk, V. & Kitagawa, I. Chemical modification of oleanene-oligoglycosides by means of anodic oxidation. Chem. Pharm. Bull. 30, 3057–3060 (1982).

    Article  CAS  Google Scholar 

  50. Kitagawa, I., Kamigauchi, T., Ohmori, H. & Yoshikawa, M. Saponin and Sapogenol. XXIX. Selective cleavage of the glucuronide linkage in oligoglycosides by anodic oxidation. Chem. Pharm. Bull. 28, 3078–3086 (1980).

    Article  CAS  Google Scholar 

  51. Pergola, F., Nucci, L., Pezzatini, G., Wei, H. & Guidelli, R. Direct electro-oxidation of d-gluconic acid to d-arabinose. Electrochim. Acta 39, 1415–1417 (1994).

    Article  CAS  Google Scholar 

  52. Thomas, H. G. & Katzer, E. Acylale durch anodische oxydation von α-alkoxy-carbonsäuren. Tetrahedron Lett. 15, 887–888 (1974).

    Article  Google Scholar 

  53. Stapley, J. A. & BeMiller, J. N. The Hofer–Moest decarboxylation of d-glucuronic acid and d-glucuronosides. Carbohydr. Res. 342, 610–613 (2007).

    Article  CAS  PubMed  Google Scholar 

  54. Torii, S., Okamoto, T. & Tanaka, H. Electrolytic decarboxylation reactions. I. Electrosynthesis of γ-substituted butyrolactones and γ-substituted α,β-butenolides from γ-substituted paraconic acids. J. Org. Chem. 39, 2486–2488 (1974).

    Article  CAS  Google Scholar 

  55. Shono, T., Hayashi, J., Omoto, H. & Matsumura, Y. The migratory aptitude in the anodic oxidation of β-hydroxycarboxylic acids, and a new synthesis of di-muscone. Tetrahedron Lett. 18, 2667–2670 (1977).

    Article  Google Scholar 

  56. Lin, D. Z. & Huang, J. M. Electrochemical N-formylation of amines via decarboxylation of glyoxylic acid. Org. Lett. 20, 2112–2115 (2018).

    Article  CAS  PubMed  Google Scholar 

  57. Schäfer, H. J., Harenbrock, M., Klocke, E., Plate, M. & Weiper-Idelmann, A. Electrolysis for the benign conversion of renewable feedstocks. Pure Appl. Chem. 79, 2047–2057 (2007).

    Article  Google Scholar 

  58. Dos Santos, T. R., Harnisch, F., Nilges, P. & Schröder, U. Electrochemistry for biofuel generation: transformation of fatty acids and triglycerides to diesel-like olefin/ether mixtures and olefins. ChemSusChem 8, 886–893 (2015).

    Article  PubMed  Google Scholar 

  59. Meyers, J. et al. Electrochemical conversion of a bio-derivable hydroxy acid to a drop-in oxygenate diesel fuel. Energy Environ. Sci. 12, 2406–2411 (2019).

    Article  CAS  Google Scholar 

  60. Holzhäuser, F. J. et al. Electrochemical cross-coupling of biogenic di-acids for sustainable fuel production. Green Chem. 21, 2334–2344 (2019).

    Article  Google Scholar 

  61. Lam, K. & Geiger, W. E. Anodic oxidation of disulfides: detection and reactions of disulfide radical cations. J. Org. Chem. 78, 8020–8027 (2013).

    Article  CAS  PubMed  Google Scholar 

  62. Swarts, J. C., Nafady, A., Roudebush, J. H., Trupia, S. & Geiger, W. E. One-electron oxidation of ruthenocene: reactions of the ruthenocenium ion in gentle electrolyte media. Inorg. Chem. 48, 2156–2165 (2009).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are grateful to the Engineering and Physical Sciences Research Council (grant EP/s017097/1 awarded to K.L. and M.C.L.) and the University of Greenwich for their financial support.

Author information

Authors and Affiliations

  1. School of Science, The University of Greenwich, Chatham Maritime, UK

    Matthew C. Leech & Kevin Lam

Authors
  1. Matthew C. Leech
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kevin Lam
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to Kevin Lam.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Chemistry thanks R. Brown and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Potentiostat

An electronic instrument that controls the voltage difference between two electrodes.

Supporting electrolyte

A chemical species that is not electroactive in the range of the applied potentials being studied, which is added to a solvent medium in order to increase its conductivity, ideally without affecting the electrochemical behaviour of the analyte.

Adsorption

The adhesion of a chemical substance (known as the adsorbate) onto a surface.

Diaphragm

Alternatively a membrane or frit, a semipermeable material that allows the flow of ions between the anolyte and the catholyte compartments in a divided cell without mixing the two solutions.

Catholyte

The electrolyte in the presence of the cathode in an electrochemical cell.

Anolyte

The electrolyte in the presence of the anode in an electrochemical cell.

Dielectric constant

A measure of the polarity of an organic solvent and its ability to insulate charge.

Ohmic drop

Also known as IR drop, a potential drop caused by the inherent resistance of the solvent, which can cause shifts in peak potential, reduce observed currents and increase the separation between anodic and cathodic peaks.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Leech, M.C., Lam, K. A practical guide to electrosynthesis. Nat Rev Chem 6, 275–286 (2022). https://doi.org/10.1038/s41570-022-00372-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41570-022-00372-y

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing