I had some requests to answer my own "Random Questions" from the other day, so here goes:
1. Does it bother you, or by contrast make you a bit proud, when you tell someone that you're a chemist and (as happens in about seven out of ten cases) they say "Oh, that was my hardest/least favorite/most boring subject when I was in school"?
Well, whether it bothers me or not, this happens all the time. Like pretty much every chemist in the world, I get to hear all about how people couldn't stand my subject in school. I take the point that mathematicians have it even worse, but it's not like we miss many of them with chemistry, either.
When people ask me what I do, I tell them "drug discovery", and I mention the diseases that I'm working on. That never fails to get some interest, and only then I spring on my listener the (often unexpected) info that this involves chemistry. Coming at it from that angle almost always leads to a good conversation, while coming at it from the "I'm a chemist" angle often leads to "Hey, look at the time!" effects. It's worth doing it in the right order, though - I like the effect when of showing that this boring/hard/useless subject actually leads to what most people find is a really interesting job.
2. How many thousands (10s, 100s of thousands) of dollars of unused equipment is sitting in dusty, unused storerooms at your company, because someone ordered it years ago and either (1) never got it to work, (2) was the only person ever to get it to work, or (3) found that it worked, but what it did wasn't worth doing that way?
Disused equipment? What is this disused equipment you speak of? Never have I seen such a thing. Why, those elaborate combichem machines in the sub-basement, they're just down there because they're so valuable. That rotating split-and-mix thingamabob and the multichannel parallel doohickey, we guard those closely.
Hah! Actually, I remember a couple of labs where this stuff wasn't in the basement at all. No, it was out there in the hoods, taking up space and slowly gathering dust, a standing reproach to everyone who walked past it. It would have been better off out of sight, but no one quite had the heart. And besides, it would sometimes get turned on for visiting groups - there was that.
3. Have you ever set up a reaction and thought "Boy, I sure hope that this doesn't work"?
I suppose that this is somewhat shameful, but yes, I have set up reactions hoping that they would fail. Usually it's been when I've had to use a particularly distasteful reagent (sodium ethanethiolate, for example), and I don't want to end up using it on a larger scale. I remember a fellow grad student presenting his work while we were trying to get our PhDs, and he detailed a deoxygenation step which only worked when his intermediate was made using a hefty excess of thiophosgene. "As fate would have it", said his long-suffering labmate from the back of the room.
And I've had less honorable instances, dating back to grad school or early in my industry career, when I was more or less forced to run a reaction a particular way even though I felt there was no chance for it to work. So yeah, in those cases I did look forward to saying "Yes, I tried your idea. And no, it didn't work any better than mine."
4. For the drug discovery people out there, what per cent of compounds you've made over the years would you guess dissolve in plain water to any real extent? Is that figure going up, or down?
The figure is hard to estimate, but it sure isn't high. Things that dissolve in straight water are hard to work with, y'know - they tend not to extract so well into ethyl acetate or dichloromethane, and they don't run so great on silica when you try to clean them up. That's worth another blog post in itself - the way that our standard chemistry techniques tend to push us away from a lot of polar molecules that might be just what we need for med-chem.
5. What, off the top of your head, would you say in retrospect is the most time-wasting chemistry you've ever ended up doing?
Tough competition. I'm tempted to say vacuum pyrolysis of corn starch to make levoglucosan, but I needed that for my dissertation, so it can't be called useless.
The real winner, in retrospect, has to be a series of reactions I did in my first couple of months in my grad school group, when I was still taking classes and working in the lab part time. I was presented with a route to a tetrahydropyran compound that we needed, a four-or-five stepper that involved an aluminum alkyne opening an epoxide, a Lindlar hydrogenation, a ring closure. . .I can still draw the damn thing on the board, now that I think about it, and it's been twenty-five years ago this spring. Being a first-year grad student, I hopped to it - and hopped right into the mud, since the route bogged down (and how) at the ring closure stage). I kept at it for a while, and then one evening I decided to look up my target compound in Chemical Abstracts.
That wasn't so easy in those stone ax and bearskin days - command-line access to CAS via a rockin' 1200 baud modem and a terminal was still a few months away. I paged through the five-year indices, and found. . .my compound. In a Tetrahedron paper. Two steps, from stuff you could buy from Aldrich, and you form the ring in the first step through a Prins reaction. I was shocked. Surely this couldn't be a known compound. Surely someone must have looked the structure up before coming up with that route I'd been given.
Surely not. And thus did my lab education begin. So you know, when I think about it, even though those first couple of months were a waste of chemicals and effort, perhaps they weren't as much a waste of time as I thought. . .