What do you do when flow requires long residence times?


There is a lot of talk about how to traverse moving from batch to flow, and how to make the process of finding a good method quicker under flow conditions. There are some factors keeping us from crossing the goal line: I’ve done it this way for so long and it works – why change (cryogenic or several mainstay transformations)?; the reaction takes too much time in a flow set up; and product survivability. I cringe when I hear these things – largely because the mantra for the last 50 years has been if it is going to 50% at 100C, then just heat it up! — Well you can call me a bit of a dummy and you would be right, but flow chemistry can offer efficiencies that a traditional batch reaction can’t — we know that — mass transfer, time spent at specific temperature can be minimized, and I could go on. Listen this isn’t a blanket that I get to throw over all chemistry, but having come from a microwave background, I think the space available for chemical transformations is untapped — we just haven’t gone there often enough……I just can’t simply buy into chemists simply doing the same reaction over and over for 20 years without finding themselves in a new reaction transformation — there is a lot of it out there and we need to untap this potential.

Let’s just improvise here and generate some discussion — -78C for an anion generation — doesn’t need to be that way for flow: the residence time doesn’t equate with 20-30 mins, then quench with an electrophile. Because the the flow in a microreactor allows kinetic conversion, the reaction can be almost immediate followed by diverting the reactive intermediate in several directions — although I have done this following cooling and anion generation in batch nearly 10000 times — and reverse added this to several other flasks….it just isn’t the best way to do it.

Reactions take longer at lower temperature — I guess you can call that a blanket. There are expanding examples of reactions and transformations that moving from batch to flow that simply do not decrease the time spent — that is without raising the temperature — or even temp/pressure if you have the opportunity. In a sense I am talking about reactions that go from 100C to 150-200C, but also reactions we don’t normally think of at temps of 350C. How many of these can you point to from experience? Well many of the products out there survive at these high temps and survive them for short and long reaction times….pharma, Ag, petro, etc. But the nice thing is that it is generally held that many transformations at these high temps can be done in a short time, and with limited “reaction time” at these high temperatures……get used to it; expansing methods are being developed.

So give you chemistry a bit more thought and challenge some of the traditional techniques used. That text book in the corner is starting to collect some dust: find some examples that would serve as a good model outside a batch process.