Habits

So I’m working in the lab and all the rotavaps on my side of the lab are busy so I go to use the one on the other side. The two on my side are both hooked up to a chiller, but the lone one has a dry ice trap. As a result, this is distinctly the third choice and is not used as much. I’m first to use it today and it needed dry ice, but the water in the bath was low too. So I got a big beaker to refill the bath, added some water. It wasn’t quite enough so I head back over to my side of the lab and refill the beaker to add to the water bath, even though there was a sink right next to the water bath I was filling. So why didn’t I use that sink?

In a word, habit.

It got me thinking about habits and our routines and how we do things.

I am, to an extent, a creature of habit. I like my routine. I see it as a mental check list that gets everything done. If I stray from my usual routine, I might forget to turn on the chiller (for example) which delays the first evaporation of the day. We have by an iterative process worked out the most efficient way to do things on a daily basis. The problem with this is when something disrupts the program, so being able to adapt to the unexpected is necessary, but as chemists working with the ever fickle world of organic chemistry, most of us are used to that as well.

But it occurred to me that the habits are helpful in another way, an important way when doing laboratory work. When things go wrong, you are already doing things right. This is where good habits pay major dividends. That goes from wearing your protective equipment even when you aren’t doing anything particularly dangerous and keeping your lab area clear so a spill doesn’t escalate. Of course, this is also when bad habits come back to bite you, those things you’ve always done and got away with. Adding extra hydrogenation catalyst to push a reaction to completion might be something you can do on a small scale, but when you do that on a multi-gram scale, you have a fire. And if you have a ton of solvent sitting around in your hood then suddenly you have a bigger fire. And if you didn’t bother putting your lab coat on to do this quick little thing, suddenly you have a big problem.

Another good habit to get into is putting things on your blog regularly. Opportunity (or just making the time) has been tricky the last few weeks, but as I believe the song goes, a good habit these days is hard to find.

My Tales of Ammonia

One of my least favorite chemicals is ammonia. Described by most as that pungent smelling gas, it is one that I would always prefer to avoid if I could. Not as downright unpleasant in aroma as numerous sulfides or mercaptans, it has instead a kind of olfactory kick in the sinuses that makes you instinctively jerk away.

What is a shame is that it is quite a useful little molecule – as the long list of producers and uses on its Wikipedia page testifies. The main use in synthesis is for dissolving metal (usually sodium) reactions, which have a characteristic (and quite beautiful) blue color. A more every day use is as an addition to chromatography solvents as ammonium hydroxide, to help the march of the amines through the silica. So my distaste for its pungency has taken a back seat to my appreciation of its utility.

My time at graduate school (at the picturesque University of St. Andrews in Scotland, by the way) was book-ended by ammonia releases that prompted evacuation of the building. I should add that I wasn’t involved in either, other than as bystander, but my understanding was that the cylinder of ammonia was only infrequently used (as would be obvious if you consider they had the same one at the end of my time there as they had at the beginning!) and had a tendency to get a bit stuck, only to open all at once and release a whole lot of ammonia in one go. Why they didn’t just get rid of the thing after the first time, I have no idea.

A more serious incident also occurred in my group while there, a grad student using ammonia got a face full after a septum popped out. It was pretty scary for a moment or two, but a colleague in the lab at the time grabbed him and got him to the sink, giving him a thorough drenching. Within a few minutes, he was all right again. It was quite shocking how suddenly something can happen in a laboratory like that. One moment as quiet as can be (given the noise of the hoods, pumps, etc), next moment bedlam breaks out.

I have done the sodium-ammonia reaction myself several times. I can’t deny it is pretty, but it is a real pain to carry out. In fact, one assignment I was given was to eliminate the sodium-ammonia step from a reaction sequence. This particular reaction was a worse pain than most, as not only was it procedurally tedious, it also didn’t give that great a yield either. But the constraints on the available space and glassware meant it could not be scaled up to any great extent either, so it became a bottle neck in the synthesis, one I was more than happy to circumvent.

Plus, it smells. Did I mention that?

Danger in Familiarity

As a chemist, I use hazardous materials every day and that is OK because I know they are dangerous so I treat them with the proper handling and respect they deserve. But are we underestimating the danger of some things we use regularly? Possibly a case of familiarity breeds contempt leads to trouble?

The first time you use a chemical, especially one you are aware is dangerous, you take special care. But it is often the case that a successful reaction will be revisited several times, by which time the chemical that you handled so carefully upon that first meeting is an old friend that never did you any harm before.

Clearly there are exceptions to this – I still feel a little nervous whenever I have used sodium cyanide or osmium tetroxide – and I am not suggesting anyone is neglecting their personal protection, just that you might not be treating it with quite the respect it perhaps deserves.

My classic example for this: concentrated acids. They are ubiquitous in laboratories everywhere. Everyone uses them, a standard chemical – and yet I bet a significant number of working chemists own clothing that has an acid spot or two on it somewhere, which is not exactly an indication of all due care being taken. I recall an undergraduate laboratory I did, where I noted to one of the professors that the chemicals we were using we all pretty dangerous. I don’t recall which ones, but I think sodium azide was in there. The professor regarded me with fond concern for my welfare and commented that he felt that the concentrated acids were the most dangerous things in the laboratory.

Another candidate for underappreciated dangers would be that entire cabinet of flammable solvents. We see that fiery symbol on it every day and it has been more years than I care to mention since I saw a bunsen burner in an organic lab, so those should be pretty safe, right? Even disregarding the additional dangers presented by ethers (peroxide formation) and possible carcinogens nestled in with the flammables (I’m looking at you, dichloromethane), the simple danger of fire in an organic lab cannot be overstated. I recall a story (which my Google skils were not able to pull up) where a faulty shelf in a flammable cabinet collapsed, causing a huge fire and destroying the lab. [UPDATE: a colleague knew the answer – it was at Ohio State University – C&E News story here] Less drastic war stories are not uncommon.

What other chemicals do you think are thought too familiar to be dangerous?

My friend phosphorus oxychloride

A recent blog post from Derek Lowe talked about the fun of quenching a reaction, thinking you are finished, only to find the chemical has its own agenda and that apparently involves climbing out of the flask and redecorating your hood. It is quite startling how using the reagent in the normal part of the reaction (when you are encouraging it to react) ends up going off without a hitch, but when you quench it to destroy the excess, well, that is when the fun really begins.

The poster child for this type of behavior is phosphorus oxychloride (POCl3). I have had the opportunity to see it in action several times and it is always surprising how suddenly it takes off.

The problem with this particular reagent is that, though it reacts violently with water, at low temperatures it is sluggish, at least partly due to not being soluble. The unsuspecting chemist sees no vigorous reaction, so adds more. What happens is you get a build-up of reagent, skulking in the bottom of the flask as far from the horrible water as it can get, but eventually, enough mixing occurs to initiate reaction, temperatures rise and suddenly you have all the reaction happening at once and giving the best impression of that fountain display in Las Vegas that it can.

It seems like the safest thing to do: default behavior when you are playing it safe is to cool the vessel and add it in slowly and for most quenches this works admirably. Certainly, you don’t want the heat in the system getting out of control. The issue is to make sure that each drop you add is reacted before you add the next one and, though it always feels strange, that is why you should add your phosphorus oxychloride quench into warm (i.e. room temperature) water with plenty of stirring and careful temperature monitoring.

It does not help, of course, that a lot of procedures call for use of POCl3 as solvent and thus in large excess, which in turn leads to there being a lot of it left at the end to dispose of. It would be preferable from a safety standpoint, not to mention environmentally, to use less in the first place. Using a cosolvent such as toluene reduces it some, though half of a large excess is still pretty much in the large excess category. Similar to the way that dimethylformamide (DMF) activates thionyl or oxalyl chloride in acid chloride formation, DMF can activate POCl3 as well. Another procedure that I have had a lot of success with is the procedure of Morris Robins [see Can. J. Chem. 1981, 59, 2601], which accelerates the reaction by addition of chloride ion, in the form of something like benzyltriethylammonium chloride. This reaction can be done in acetonitrile and takes you from refluxing in neat phosphorus oxychloride for several hours to 50 to 80 C with the reaction complete in a few hours at most (I had one that was done in 30 minutes and would start to decompose if it ran too long). A lot of the problems with this type of chlorination or dehydration procedure is that the initial reaction is fast but loss of the phosphorus intermediate (somewhere between phosphate and PO2Cl2) is slow. This is also why sometimes you can start this reaction and it seems to have done something, but when you stop it (prematurely), the intermediate just hydrolyzes back to the starting material and you have wasted your time. The chloride increases the rate of the slow step. And you can get away with uses several equivalents of POCl3 instead of the less than scientific ‘lots’.

What is interesting about the frequency of incidents with this is a thread with common accidents in chemistry. They happen when you think the danger is passed. With very dangerous and toxic chemicals like hydrogen cyanide, everyone is very careful and accidents are rare as a result. It is when you are underestimating what is in your flask that you can get into trouble.

Dangerous Work

I’m not going to be shaking anyone with revelations when I say that working with chemicals is a dangerous business. The list of warnings on the labels of some chemicals are enough to make one consider taking up something safer. Most of us have horror stories of spills or fires of some sort. Recently in the news there have been several chemical accidents – an accident at a Bayer plant, in which several people were treated for chemical exposure, the tragic death of a UCLA research assistant and another death due to TMS-diazomethane exposure.

And yet, I have not seen any data concluding that chemistry is a negative on your life expectancy nor have I contemplated abandoning a career in the field due to safety concerns.

It is certainly true that working in a research lab is much less dangerous than some vocations. The chemicals (no matter what you might think) are not actively out to get you, unlike enemy soldiers. And while that is also true of a fire fighter, they are clearly being brought into a situation that is getting out of control. When we walk into a lab full of toxins and flammables, we know what we are doing and we thus treat our day’s work with the proper respect. We use gloves, lab coats and fume hoods to keep us safe and away from the danger. Which, incidentally, why I was so shocked by the earlier mentioned TMS-diazomethane story, because the fellow was working with the chemical while the fume hoods were turned off due to maintenance. When hoods go down where I have worked, that is a cue for everyone in there to step away to their office or out of the building.

Accidents seem to happen not when things are going along as normal but when people are in a hurry. You didn’t have time to review this reaction before doing it because you have a deadline to meet. You have been shown how to do this reaction once, but the teacher is too busy to look after you again and now you are flying solo. You have the wrong piece of equipment and it will take too long to put it right. Under pressure like this, you make mistakes and poor decisions. These things go a lot smoother when you have the experience, the proper equipment and no looming need to be done and onto the next thing.

I have made and used diazomethane many times. I always did it using the proper diazomethane kit, with the smooth glass joints, everything properly chilled and behind a blast shield. For those who don’t know (and didn’t read the Wikipedia link), diazomethane is toxic and also known to explode under certain conditions. The first few times I did it, I took great great care over it. I never had any problem (which can occur mainly if you allow the diazomethane to concentrate – while it is in solution, there is little issue). At the time, I was using it regularly, we made it in relatively small batches (no more than the equipment would allow) and stored what we made in solution in the freezer. This is one reagent that my colleagues expressed a significant amount of fear over. But it is like any other dangerous substance we use in the laboratory: if you use it correctly, there will be no problem. Show confidence in yourself and your engineering controls without slipping into arrogance – in which you begin to neglect the safety measures and treat the chemical without all due respect, all because you’ve done it 10 times already and nothing bad ever happened.

Safety in the work place is an important issue, especially when the work place has so many things in it that can do you harm. Ironically, several of the incidents I can recall from my experience were not related to chemistry at all – tripping hazards and bumping heads on open cabinet doors (which is a specialty of mine, by the way). Something that could happen anywhere.

Be careful out there.