Month: June 2018

Goodness pressure is important in continuous flow. In fact, one of the major advantages of flow vs batch is how easy it is to apply pressure. The main benefit of pressure for a homogeneous liquid reaction is that the solvent can be heated above its standard boiling point, allowing you to give the kinetics of your reaction a bit of a kick up the proverbial and reduce the time needed inside the reactor, and thus, increase your throughput. It does go without saying though that this approach only applies to chemistry robust enough to take it, and those who are at the final stage of a synthesis of a large natural product, probably need to take things more gently.

That said, there are other reasons that pressure is important – we can discuss thermodynamic, physical chemistry functions like the Gibbs volume of activation if you like, but I think before we need to think too hard about that, pressure has more immediate benefits. Preventing gas evolution from reducing residence times is key to maintaining good conversions, and pressure is vital in gas/liquid reactions for making sure the liquid is saturated with the gas for the reaction to take place.

But, there is a problem. Solids, particulates, precipitates of any kind can cause a real problem with needle and seat-type back-pressure regulators, causing inconsistent pressure management at best, and blockages at worst. Enter the peristaltic BPR. The SF-10 pump uses the Vapourtec V-3 pumps and can run as a pressure regulator. Now, the maximum pressure is 10 bar, but that’s more than enough to superheat most solvents quite a long way and the continuous release of pressure, instead of the “open-closed” binary state of a needle BPR, allows for much smoother, more consistent pressure control. The real piece de resistance though is that the SF-10 can handle solids. Not just the odd crystalline precipitate either, I’ve used these pumps to control the pressure of slurries loaded up to 100 mg/ml without any trouble and now it’s my go-to method of controlling pressure, simply because I know that it will just keep working even if I haven’t got my down-stream solubility quite right (which I never have, by the way).

For more information about Vapourtec, click here.

Quick screening of reaction partners is clearly very important for discovery, and one of the things I’ve been working on a lot lately is automated library synthesis. I think this is one of the major advantages to being able to use a flow protocol; a great many of the things we do as chemists are straightforward, repetitive and time-consuming. Any technology that frees us from the laborious tasks and makes us available to work on complex challenges simply has to be an improvement.

We’re able to use a range of different liquid-handlers, and we recently took delivery of a small handler that fits just nicely in my fume hood. I use it with pretty much everything now, sometimes to load reagents, but often just as a collector, allowing me to schedule a list of reactions in the morning and leave it running through the day while I work on other things. I’ve needed to run various analyses on the library compounds, so have gone up to 5 ml loading loops, which at the concentrations I’ve been using give me plenty of material to isolate and analyse in whatever way is needed.  There have been a few challenges along the way; one photochemical library has been producing cyclobutyl adducts from a range of maleimide and uracil derivatives, added via a [2+2] to ethene. The problem is that ethene gas has variable solubility in the different reagent solutions, sometimes most of it dissolves into the liquid, reducing the flow velocity and increasing residence time, then a different substrate is added by the handler and the ethene now doesn’t dissolve, increases flow velocity and pushes everything out of the reactor faster. A bit of a worry when you’re collecting your product automatically.

The solution was quite straightforward for me, I put a UV detector inline and made my collection window larger than it needed to be – I wasn’t carrying out an optimisation so only collecting the steady state wasn’t as important. A more elegant way to work would have been to use the UV to start the collection when it detected the material, I’ll have to do that next time. Either way, the liquid-handler has liberated me from the fume-hood for most of the day, which has enabled me to be more involved with applications support and product development, all the while keeping the output of the lab the same. Of course, when you find something interesting, you’re always going to want more of it but then that’s the advantage of a flow protocol at the lab scale; just run longer.

Ideal.

For more information about Vapourtec, click here.