What’s brown and highly corrosive?

“Fatal if inhaled”. There. That got your attention.

It certainly got mine! I was preparing the COSHH assessment for a recent application note when I saw that alarming statement, which on the SDS is then followed by the rather helpful advice “do not breathe fume/vapour”, just in case you hadn’t fully understood the concept of fatal if inhaled…

Happily, things like this are made a little simpler with flow chemistry. The plan was to carry out the photochemical bromination of a range of different substituted toluenes, using molecular bromine in solution, and see how easy it would be to increase the throughput of the reaction. As the bromine does present a fairly significant hazard, Dr Roger Moses joined me in the lab to share his experience and provide Devon vs Cornwall related banter (cream and then jam, obviously).

With the bromine in solution, which when I think about it I ought to have made using an SF-10 to deliver the bromine instead of using a Pasteur pipette, working with it in flow was very straightforward. It was very pleasing to see the orange-brown reagent mixture going into the reactor and colourless product coming out of the other end, although thick gloves were needed for everything, as the HBr generated in a stoichiometric amount, can fume off of the product vial. A little wash with some thiosulfate solution to pick off any bromine that might still be lurking about, and then onto the HPLC to get a feel for what’s going on. As far as boosting throughput goes, this really was about as easy as it gets; the UV-150 is very efficient, so even with residence times of just a minute we were seeing conversions of 80% or so. We quickly got up to around 15 grams per hour, and then chickened out pushing any further – the benzylic bromides are well known for their lachrymatory properties, and cleaning up a bunch of essentially tear gas didn’t seem like a fun way to spend the afternoon.

For more information about Vapourtec, click here.

Return on the 27th of October for the next blog about using n-butyllithium in continuous flow

Controlling the electrons

Perhaps unsurprisingly, a key aspect of electrochemistry, is the electricity.

I know, ground-breaking stuff! As I’ve discussed a lot recently, the Ion electrochemical reactor has been developed with a lot of different features, like temperature control and operation under pressure, but I realised I’ve never actually mentioned the important bit – the electrics.

The Ion will have its own power supply, but up to this point I’ve been working with an early prototype. A really important feature has been that I can set the desired current and monitor the change in the voltage, or the other way around. Mostly I have been working in a current limited mode, and been adjusting the concentration of my electrolyte to achieve the voltage that I need – this is quite important, because if you have too high a voltage your reagents or products can just be pulled apart and you get ions all over the place. Not enough voltage, and nothing happens.

Another handy thing about fixing one parameter and allowing the other to vary is that I can monitor that variation with time – in this case I have been using an external logging device to watch changes in the voltage, but the Ion’s own power supply will come with that function built-in. This is useful for a couple of reasons: firstly, it makes it very clear when the substrate has made it into the reactor. The system solvent does not contain any electrolyte, and so the conductivity is poor, and stays constant. As the substrate enters the reactor the conductivity increases and so the voltage (in my case) needed to achieve the current reduces:

A successful electrochemical reaction

It makes it clear when the reagent is in the reactor which is important for collecting the steady state for analysis. It can also make it very clear when something has gone wrong:

A reaction where a partial short-circuit has occurred

in this image, a build-up of degradation products caused a small short-circuit in an early prototype. The good news is that tracking the voltage with time enabled me to see this right away and stop the experiment, rather than keep running an expensive starting material. The design has also been improved to prevent short circuits like this from happening.

For more information about Vapourtec, click here.

Return on September the 26th for the next blog on working with bromine in continuous flow