Talking as I was the other day about flow chemistry makes me think again of a topic that I find interesting, perhaps because it’s so difficult to refute anything: the counterfactual history of science. It’s a bit perverse of me, because one of the things I like about the hard sciences is how arguments can actually be settled (well, at least until new data come along that upset everything equally).
But here goes: if flow chemistry does catch on to become a widely accepted technique – and it may well deserve to – then what will have taken it so long? None of the equipment being used, as far as I can see, would have kept this all from happening twenty-five years ago or more. Some pumps, some tubing, a valve or two, and you’re off, at least for the simplest cases. Some guy at Pfizer published a home-made rig that many people could assemble from parts sitting around their labs. So why didn’t they?
Easier to answer is why flow chemistry didn’t become the default mode of organic synthesis. The requirement for pumps and pressure fittings made it unlikely to be taken up back in the days before HPLC systems were so common. Something could have been rigged up even a hundred years ago, but it would have been quite an undertaking, and unlikely to have caught on compared to the ease of running a batch of stuff in a flask.
But since the 1970s, the necessary equipment has been sitting around all over the place, so we get back to the question of why it’s finally such a hot topic here ins 2007. (And a hot topic it surely is: the other day, Novartis announced that they’re handing MIT (just down the road from me) a whole bucket of money to work out technology for process-sized flow reactors).
My guess is that some of it has been the feeling, among anyone who had such ideas years ago, that surely someone just have tried this stuff out at some point. That’s an inhibitory effect on all sorts of inventions, the feeling that there must be a reason why no one’s done it before. That’s not a thought to be dismissed – I mean, sometimes there is a good reason – but it’s not a thought that should make the decision for you.
There’s also the possibility that some of the people who might have thought about the idea didn’t see it to its best advantage. The ability to have high temperatures and pressures in a comparatively small part of the apparatus is a real help, but if you’re thinking mostly of room-temperature stuff you might not appreciate that. Ditto for the idea of solid-supported reagents (which, in its general non-flow form, is another idea that took a lot longer to get going than you might have thought).
And there’s always the fear of looking ridiculous. Never underestimate that one. Microwave reactions, remember, got the same reception at first, and that must have gone double for the first people who home-brewed the apparatus: “You’re running your coupling reaction in a what?” I can imagine the rolling eyes if some grad student had had the flow chemistry idea back in the 1980s and starting sticking together discarded HPLC equipment and hot plates to run their reactions in. . .