Frustrations of Reproducibility

A few weeks ago I finally found the wherewithal to head off into the lab to try and replicate a very interesting result one of last years crop of project students had obtained. They had been investigating a potentially new catalyst system and had obtained a rather intriguing and somewhat unexpected result by NMR.  The reaction conditions were tantalizingly simple and mild, the result rather nifty and well worth further investigation. And I had the left over catalyst and reagents necessary to conduct the simple test.

Nothing. After the required time stirring away (and at a warmer time of year for ‘room temperature’ than the student’s attempt was), no change in the NMR at all. At this point I started bug checking. The catalyst was unlikely to decompose, being of a rather robust nature not prone to falling to pieces at room temperature in a sample vial. The substrate was the same bottle (and the anomalous product was not an impurity in the bottle – I checked!). The other reagents were, if anything, fresher than the student had used so that was a potential source of error – what if the older reagents were contaminated by some mystical substance that gave the reaction the necessary oomph to go? And the only other thing that could possibly have been the issue, which I’ve only just realised while writing this post* is whether the student put a stopper on the flask or not.

Could something as simple as a stopper on the flask be important? Well yes, it frequently is. Air sensitive stuff isn’t going to take too kindly to a steady flow of oxygen in the flask, volatile solvents or reagents aren’t going to hang around for long if given that sort of freedom. But in a reaction where the reactants are water and other things that don’t much fancy evaporating at room temperature, it wouldn’t necessarily be a detail worth recording in a laboratory note book. The reaction could have been conducted with or without the stopper without any of the common problems occurring. Except, if the stopper was left off, the reaction may have worked better – it was an oxidation after all.

Unfortunately I’m now in that itchy limbo where I have a testable hypothesis (leave the stopper off, see if it works), but I ran out of substrate in the last attempt. So I’m waiting for some more to arrive (hopefully it has been ordered), and also because we need that to test a fragile little complex as a catalyst that seems to decompose despite being well treated according to the instructions in the paper we’re following. I want to try the reaction…and I’ve already looked, there aren’t any similar substrates floating around – we’d have used them in the project in the first place.

The fragile little compound is turning out to be a grade A PITA** as it is needed for a new undergraduate experiment and will be made in class one week, stored for 7 days, then tested as a catalyst. If it doesn’t survive our latest attempt at storage, it will be back to the drawing board for that experiment. Shame really, as it was the magical combination of relatively inexpensive starting materials (no rhodium trichloride in sight), a nice paper with detailed methods for making and testing the molecule as a catalyst, and plenty potential for a good class data pooling investigation into the effects of varying variables on results of the reaction.

*see blogging is useful for actual bench research

** Pain In The Arse


3 Replies to “Frustrations of Reproducibility”

  1. If I were in your shoes, I would try the no stopper reaction. You didn’t say what kind of reaction it was, so I can’t give you much more advice that whats below:

    Do you think they used old reagent that might have been wet? Add some water (did you see that Blog Syn post about water being a secret ingredient in IBX oxidations?)
    Did they use solvents that form peroxide (e.g. thf, Et2O, dioxane) ? Add some peroxide
    Did they use old chlorinated solvents? They often have HCl in them if they are old, so add a drop of HCl.

    Good luck!

  2. Yep, pretty much the plan. We were trying to develop a new catalyst for epoxidation but seem to have a catalyst for allylic oxidation instead.

  3. Ah, in that case definitely try with and without light as well, and exclude oxygen (unless that’s your source of O for the epoxidation). You want to avoid too much radical reactivity, which can promote the allylic oxidation. The industrial epoxidation of ethylene doesn’t work with propylene, it just leads to oxidation to CO2 because those darn pesky allylic C-H bonds are too amenable to radical oxidation.

    Cheers and good luck!

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