The Phantom Menace

When I started my PhD one of my then colleges spent months trying to make something that was sitting on a shelf in the chemical store room less than ten feet from their bench. Could there really be anything more frustrating? Well yes there could. Imagine finding a new catalytic process or synthetic transformation only to find, perhaps months or years down the line, that it was a contaminant in one of your reagents or starting materials driving the reaction- maybe something that is peresidented to do the exact chemical transformation you have (re-) discovered. I’m sure this has happened to many people over the years, particularly in the case of metal catalysed reactions in which very low levels of metal can still be highly effective in catalysis. A review paper by Kazuhiko Takai some years ago describes several examples of reproducibility in organometallic chemistry that were eventually attributed to the presence of traces of a second metal.1 Bolm has also published a review specifically on the effect of trace metal impurities in catalysis. In 2005 Arvela et al re-evaluated their Pd free Suzuki chemistry, only to find that palladium contamination at 50 ppb in the commercial sodium carbonate they used as base in their reactions was responsible for generation of the biaryl not, as previously published, a transition-metal free pathway.3 I’m sure that was a particularly bad day for the team. 

Another historical example I’ve come across is the organochromium(III) catalysed Nozaki-Hiyama-Kishi coupling of an aldehyde with an allyl- or vinyl halide. The success of the reaction was found to be dependent on the source of the chromium(II) chloride catalyst and it was later found that traces of nickel impurities were catalyzing the carbon-chromium bond forming step. Subsequently nickel chloride was added as a co-catalyst.4 Buchwald and Bolm also shed some doubt on iron catalyzed coupling reactions, suggesting that traces of copper were having a significant effect.Other reports include a dramatic effect of catalytic lead on the Simmons-Smith formation of alkyl zinc reagents from iodoalkanes and trace metal effects on Sonogashira coupling reactions.6

A new twist on this conundrum caught my eye in a paper published recently by Ananikov in ACS Catalysis with the unnerving title “Phantom Reactivity in Organic and Catalytic Reactions as a Consequence of Microscale Destruction and Contamination-Trapping Effects of Magnetic Stir Bars”.7 The paper was picked up by popular science journals and also found its way into a Nature editorial and Chemistry World article.

Now everyone has their lucky stirrer bar. And it’s usually fairly battle scarred. But in a cruel twist of fate it would appear that Lady Luck also has an interest in science. In a kind of parody of homeopathic medicine your lucky stirrer bar may contain a memory of past reactions. The PTFE can become impregnated with metals that remain ready and waiting for that next catalytic reaction. The synthesis and characterization of Polytetrafluoroethylene(PTFE) has just been reviewed and is a fascinating read in itself (Figure 1b).9

Figure 1: a) PTFE stirrer bars b) Discovery of Teflon by Roy Plunkett (DuPont) from polymerized tetrafluoroethylene (re-enactment, 1938)

Ananivov’s team found that random samples of “cleaned” stirrer bars obtained form different labs, many of which were visibly discolored, had surface defects when examined under scanning electron microscopes. Other X-ray techniques revealed the presence of precious metal nanoparticles (Pt,Pd, Au) and computer modelling suggested that these nanoparticles could bind to the polymer with some tenacity. They also found that these particles could leach into reaction mixtures and were detectable by Mass spectrometry. In the case of Pd the activity was sufficient to catalyse a “metal free” Suzuki cross coupling! This is not altogether a surprise- a paper published some time ago describes turning Teflon-coated magnetic stirring bars to catalyst systems with metal nanoparticle trace deposits.11 It’s now possible to buy such things from commercial suppliers. 

This paper is important on several levels. It highlights the need to run control experiments with previously unused stirrer bars- particularly for catalytic reactions, but also to consider possible contaminants in reagents (and solvents). On larger scale the vessel history should be considered, or dedicated vessels used for catalytic processes. From a glass half full perspective, purposeful generation of nanoparticles on the surface of a Teflon stirrer bar (building on the work highlighted above) could be broadened for a wider range of reaction modalities. 

At least no-one is claiming that the magnet is having an effect….12

To torture this subject a little further an interesting article on enhancing and extending the lifetime of heterogeneous catalysts- termed “catalyst farming” has just appeared as an Edge article in the journal Chemical Science.13 The idea is that active catalytic species can be inactivated during a catalytic process leading to reduced efficiency and that based on the principles of the crop rotation system used in agriculture, the catalyst can be rejuvenated and its lifetime extended by alternating different catalytic reactions, most likely through reactivation of the catalyst surface. In the paper they looked at Pd nanoparticles deposited on nanometric TiO2. The “crops” were Ullmann homocoupling, Sonogashira coupling and olefin isomerization/reduction. The results showed a positive effect (it wouldn’t have been published if this were not the case). In the paper they go on to define “catalyst farming” as “target product rotation is the practice of performing a series of dissimilar or different types of catalytic processes using the same catalyst in sequenced reactions. It is done so that the catalysts are not deactivated by a fixed set of reactants. It helps in reducing catalyst deterioration and increases longevity and product yield”. 

As an effort to improve sustainability it ticks the box, but in reality there is a long way to go before its anything more than an academic curiosity.   

John Studley, 11thJuly 2019


  1. Trace amounts of second metal elements can play a key role in the generation of organometallic compounds: K. Takai, Bull. Chem. Soc. Jpn. 2015, 88, 1511-1529.
  2. Trace metal impurities in catalysis (tutorial review): C. Bolm et alChem. Soc. Rev. 2012, 41, 979-987.
  3. A Reassessment of the transition-metal free Suzuki-type coupling methodology: R. Arvela et alJ. Org. Chem. 2005, 70, 161-168.
  4. Catalytic effect of nickel(II) chloride and palladium(II) acetate on chromium(II) mediated coupling reaction of iodo olefins with aldehydes: Y. Kishi et alJ. Am. Chem. Soc. 1986, 108, 5644-5646.
  5. On the role of metal contaminants in catalyses with FeCl3: S. Buchwald et alAngew. Chem. Int. Ed. 2009, 48, 5586-5587.
  6. A dramatic effect of a catalytic amount of lead on the Simmons-Smith reaction and formation of alkyl zinc compounds from iodoalkanes. Reactivity of zinc metal: activation and deactivation: K. Takai et al, J. Org. Chem. 1994, 59, 2671-2673; Catalysts for the Sonogashira coupling: the crownless again shall be king: H. Plenio, Angew. Chem. Int. Ed. 2008, 47, 6954-6956.
  7. Phantom reactivity in organic and catalytic reactions as a consequence of microscale destruction and contamination-trapping effects of magnetic stir bars: V. Ananikov et al, ACS Catal. 2019, 9, 3070-3081.
  8. Hidden flaws in common piece of lab kit could botch experiments: Nature 26th March 2019, Research Highlights; K. Welter Chemistry World, 22nd March 2019.
  9. Polytetrafluoroethylene: synthesis and characterization of the original extreme polymer: B. Amedur et al, Chem. Rev. 2019, 119, 1763-1805.
  10. The devil in the details: The influence of trace metal contaminants in modern organometallic catalysis: J. Macor, 2011, literature seminar.
  11. Turning Teflon-coated magnetic stirring bars to catalyst systems with metal nanoparticle trace deposits – A caveat and a chance: C. Janaik et al, Appl. Catal. A2012, 425–426, 178-183.
  12. New possibilities for magnetic control of chemical and biochemical reactions: A. Buchachenko et alAcc. Chem. Res. 2017, 50, 877-884.
  13. Catalyst farming: Reaction rotation extends catalyst performance: A Elhage et al, Chem. Sci. 2019, 10, 1419-1425.