My mention yesterday of the number of starting materials needed for drug synthesis prompted a reader outside the industry to ask just how many I might be talking about, and how these things are managed. I looked over the paper being discussed, just for an example, and for its three drug syntheses it needed a total of four commercial starting materials, twelve different reagents, and three solvents, and that doesn’t sound at all untypical.
What happens is a classic “long tail” distribution. There are reagents and solvents that are so widely used that they’re almost invariably kept in some sort of common storage area in a lab and/or found in smaller quantities at each bench. These are the potassium carbonates, sodium sulfates, ethyl acetates, and tetrahydrofurans – they come up constantly, and they need to be readily available. Past those are chemicals that are just a bit less universal, but that you can be sure of finding if you look in your own collection or the people next to you. In that category, I’d put things like the various palladium and platinum catalysts, lithium hydroxide, amide coupling reagents like EDCI and HATU, simple amines like morpholine or pyrrolidine, etc. If you run out, you know that someone’s got a bottle of the stuff around. They have to. It’s a med-chem department, and who ever heard of a med-chem department without a bottle of piperidine or some copper iodide around?
But after this, it’s long tail time. There are an awful lot of cyclic secondary amines once you get past those three I just mentioned, and at one time or another someone has probably wanted to put one of them on their scaffold. So these things are stored in the stockroom, an ever-expanding collection of commercial reagents and in-house intermediates. Every good-sized chemistry department has to devote effort, staffing, and resources to the problem of storing and keeping track of these things. I’ve seen a lot of different systems used over the years, and it’s safe to say that no perfect one exists.
One thing that varies is how many reagents people are allowed to keep at their own bench or hood. Some places are OK with people having what are nearly mini-stockrooms of their own (“Go see Pete; he’s got a big collection of stuff like this”), while other departments actively discourage this sort of thing and practice “reagent decluttering” as a rule. No matter what, though, every bottle has to be marked and noticed, usually with some sort of bar-code system. But quis barcodet ipsos barcodes? Someone has to keep track of how the reagents move from the labs to the stockroom and back again. Even worse, the chemists are constantly going to be borrowing stockroom reagents from each other and not returning them to the owners of record, because that’s what we do. In my own experience, depending on the chemists themselves to keep these inventory systems up to date is a doomed endeavour. We have other stuff going on, and we’re always going to just return that reagent as soon as we’re done with it, or bar-code those bottles that came in just as soon as we’re done with that other thing. Run things like that for a few months, and no one knows where anything is at all.
You need people who do nothing else but keep track of the compounds, a staff to round these things up and keep order back in the stockroom, and you’ll have to make sure that the chemists are kept out of there or you can kiss that order goodbye. What you’ll usually see is some kind of ordering and lab delivery system to each bench, and on the other end, bin or designated area for reagent return, which is sometimes divided into “Back to the Stockroom” and “Empty/Dispose” categories. All this costs money, but if you don’t pay it, you’ll pay in the less visible but even more expensive currency of people wasting time wandering around looking for reagents, or people just not setting up particular reactions because they can’t find the darn coupling partner and the heck with it. Even the better-managed shops need to call a halt occasionally for an Inventory Day or two, where everyone’s bench, hood, cabinets and fridges are scanned to reset all the bottle locations and ownerships.
Another aspect of inventory management is dealing with duplicate bottles and clearing out things that are no longer useful. A good inventory system will cut down on the duplication, because people will be able to see that there are already supplies of Reagent X in house (although some people will always order a fresh bottle just for themselves). That fresh-bottle behavior is particularly acute, naturally, for those reagents that are known to deteriorate. A jar of sodium bicarbonate from 1927 is just as good as it ever was, but a bottle of aniline from last year will already have turned red or even black by now. It was probably at least yellow when it came in the door – freshly purified aniline is clear, but I’ve only seen a couple of samples of clear aniline in my life, because it reacts with atmospheric oxygen and it’s all downhill from there. (If you go back to the really old literature, you can see substantial confusion about just what aniline’s boiling and freezing points really were, because everyone was working with sample of different purity).
Oxygen and ambient humidity are what wear on most reagents that are capable of wear (some amines will pick up carbon dioxide as well). The beloved “palladium tetrakis” catalyst (that we all use even though there are better catalysts out there for any given palladium coupling if you look) is another example. A fresh bottle is a beautiful light, clear lemon yellow, but over time the bloom fades, a bit of orange creeps in that will sing in deeper and sadder tones of red and brown if you give it long enough, and if you’re chucking brown tetrakis into a reaction and expecting it to work, you are a lazy hack indeed. Generally, it’s the chemists out on the bench who decide that a given bottle of reagent has lost its zing, and are expected to dispose of it and put it the empty bottle back in the bin to be removed from the system. Personally, I have tended to order the stockroom bottles that have newer-looking barcodes on them in the inventory software, and I’m sure I’m not the only person who does it, either.
Another feature of a long-running stockroom is the number of reagents in it that were once articles of commerce but are so no longer. These things (as long as they haven’t gone bad) are actually quite valuable, as you’d imagine. I also enjoy the sight of older label styles (and apparently I’m not alone). Once in a while I’ll see the “good old Aldrich” labels from the 1980s (and probably before) when I was first starting to work in the lab. (A slightly modified version is here!) In fact, you can sometimes even see labels of whole supply companies that have disappeared – for years, Lancaster Synthesis bottles would appear in my stockroom orders even though that name was no more to be found in the real world.
So that’s a long answer to the question of “How many chemicals do you people have around?” The answer is thousands, of all degrees of purity, age, popularity, and utility, and keeping track of them is a full-time job!