Org Prep Daily

August 11, 2009

Dear ACS journal editors – please return from your vacation soon

Filed under: lab destruction, lit highlights — milkshake @ 1:14 am

dovolena credit: National Geographic ‘Photo of the day’

The spectacular “NaH catalytic” oxidation recently published in JACS has been thoroughly covered elsewhere. I would like to bring your attention to another jaw-dropping paper that just came out in Org Letters:

Acetophenones and 1-aryl-ethanols are oxidized to benzamides by heating the material with 3 – 4 equivs of iodine and ammonia in a pressure vessel. There is only a passing reference and footnote that “nitrogen triodide might form in the mix.”

In fact, NI3.NH3 readily precipitates upon mixing iodine with aqueous ammonia. (The products vary; a gradual iodine addition to a large excess of ammonia yields ammonium iodide and nitrogen.) Nitrogen triodide is a notoriously super-sensitive primary explosive. I spent some time hospitalized in eye clinic when I was ten years old – my corneas got burned with iodine and my eardrums ruptured because of playing with a spoonful of nitrogen triodide. (The window pane flew out and I was thrown to the ground by the blast;  it took me half a year to fully recover and this all was from few grams of dry material going poof, unconstrained). I cannot warn strongly enough against mixing iodine with ammonia in a pressure flask and then heating the stuff up!

The authors run these experiments on a 1 mmol scale and they give no details about the order of addition. Since the transformation is pretty useful – with a good substrate scope and it looks simple enough (its done in water) –  sooner or later some innocent person is bound to mix up a big batch in the wrong way – and as he screws on the the pressure vessel cap he is gonna blow himself up into a mauve cloud

November 25, 2008

More lab disasters 2

Filed under: lab destruction — milkshake @ 6:06 pm

When I was in high school, I got free run in a chemistry lab that belonged to a youth center. I was trying to synthesize papaverine, and this was completely above my ability (and the lab resources) but I was very persistent. The key building blocks for papaverine are homoveratric acid and homoveratryl amine, and I set out to make them by myself: I had several bottles of catechol to start from – my problem was how to methylate it, I could not just buy stuff – I had to go by with what was in the stockroom.

First I made lots of methyl iodide, from red P + iodine and methanol – refluxing and distilling it on the bench so I know how methyl iodide smells – but the methylation was messy. Next I tried to make dimethyl sulfate from sulfuryl chloride and methoxide in situ, and it worked to some degree – the vanilla smell of guaiacol was everywhere – but again I could not isolate anything from the mess. So my next idea was to use diazomethane made from nitrosomethyl urea.

So I was cooking and then distilling AcNH2 on a grand scale, from AcOH and urea – and this went quite well (apart from the all-pervasive mice urine-like smell of acetamide) and then I was to carry out the Hoffman degradation.  When one uses concentrated aq KOH and bromine, the in-situ generated MeNCO reacts with a second molecule of acetamide to produce MeNHCONHAc, an intermediate for preparing nitroso methylurea; I needed it for a large-scale diazomethane reaction so I did it on a mol scale on the first run.

The procedure called for Br2 to be added into AcNH2 + 30% aq KOH mix in a 1L flask, then gently heating the mix until a rapid gas evolution commenced. Since I scaled up the preparation by a factor of twenty on the first run, and I did not have a 20L flask, I used the biggest flask I could find, a 4L Erlenmeyer, and loaded the stuff up; it all fit in there. But then, the mix did not wait to be gently heated and instead jumped out at me all at once.

I usually did my work without glasses, on the bench – but this one time I put goggles on and it was well worth it. The hot KOH + KOBr solution rained all over the place and bleached my hair blond; also my T-shirt and jeans ended up with white vertical stripes. A colleague stood nearby and saw the whole thing and dragged me into shower.

Eventually I did make some nitrosomethyl urea and diazomethane but never finished the papaverine project. No explosion, poisoning or other injuriy happened during all these crazy experiments. But there was another like-minded highschool kid, repeatedly working on some chemistry involving acetone cyanohydrine, and he was making it from acetone and NaCN, in our little fume hood with a lousy fan-driven exhaust. I think he never finished his project either but I remember once we were going down the stairway and he was saying “I don’t know if this exhaust really works ’cause I was smelling hydrogen cyanide this time a lot” and then we got outside there were two dead pigeons on the grass and we looked up and the exhaust from our fume hood was looming right above us…

November 13, 2008

More lab disasters

Filed under: lab destruction — milkshake @ 3:41 am

Ψ*Ψ has a new post on undergrad lab disasters, I would like to add few more of my own making, from two decades ago:

In the junk-room of our chemistry department I found an ancient belt-driven vacuum pump that operated on 380V three-phase AC. I brought it from the basement into our freshly-renovated lab, put it on the bench, plugged it in to see if it worked – and it did. Unfortunately the 380V AC wiring must have been wrong in our lab (we never used 380V plug in there before) or the phase order in the pump itself was switched. At any rate, the motor started spinning backward and the pump pumped out its oil from the inlet hole at once –  a gallon of black muck that hasn’t been changed for eons. The intlet had a short piece of rubber hose on and it worked like a nozzle – directing the stream of goodness at the high ceiling, right in the middle of the room whence it rained down all over the place. This mishap actually shut down our lab for two weeks as the oil-soaked plaster had to be knocked off down to the brick and concrete in order to make the new plaster stick.

Some months later I was working as a guest student in another lab (in another building, at another school) – and they had a gas-powered water heaters installed above the sinks because their building lacked central hot water. It was a strange and dangerous thing to have in the lab (right next to the  organic solvent bottles); and the last person in the lab always made sure to turn off the pilot lights before leaving.  One early morning I was washing my hands and water was coming out freezing cold – the  pilot light was off –  so I grabbed matches and without turning off the running water (and the stream of gas), l lit the pilot.  A yellow fireball shot up and the casing flew off from the heater infront of me, with an impressive bang. When my ears stopped ringing  I could hear a calm voice from the opposite corner of the lab where a colleague sat at her desk: “Mr. Borivoj, I promise that the next time I’ll pour my coffee over you.”

The same colleague a week later decided to clean up and inventorize all her glassware – she emptied her drawers and put it all on a long bench. Meanwhile I was distilling 0.5L of old and nasty-looking  N-methylmorpholine to which I added lots of calcium hydride – and when I finished I had CaH2-rich leftover sludge in the distillation flask. I was asking around if it was OK to quench it with ethanol (I had quenched NaH and BuLi before) and a faculty dude said I should go right ahead; I did not realize they probably did not work much with CaH2 in that lab.  So I was carefully adding ethanol with cooling, the bubbles were coming out, calm and nice.  One hour later (back from lunch) I added some more ethanol – no bubbling anymore – so I was certain I could pour that into the waste, and I went to the sink to dilute the sludge with water a bit so that I could pour it out. Suddenly it became clear that ethanol does not really quench CaH2, and water does. The  mud volcano in my hands erupted away, spewing the hot lime and fishy amine on the nearest bench – all over that clean and inventoried glassware. The owner again took it  calmly – she just muttered “We have to assign you a working space in the hallway”…

August 19, 2008

Our lab you must not enter

Filed under: lab destruction — milkshake @ 10:04 pm

When I was fired from my first lab in college for the phosphine stinkup, no-one volunteered to have me so for awhile I had a bench and hood in the teaching labs. I was there alone, enthusiastic and without supervision. The glycidol story was mentioned already; I will describe two more memorable experiences:

Burning acrolein: We couldn’t buy things from Aldrich under communism and acrolein was unavailable from domestic supliers. Eventually I decided to make my own; there was an ancient lab procedure from glycerol by pyrolytic dehydration over KHSO4. (The yield is dreadful but we had a drum of glycerol in the stockroom).  I did it on a grand scale and I ended up with about 0.5L of crude acrolein containing lots of water. To remove the water I got the idea of using magnesium perchlorate as a drying agent – we had a big bottle of that stuff on the shelf and I was reading somewhere that Mg(ClO4)2 was a potent desiccant comparable to P2O5 in its dehydrating proves. No wimpy sodium sulfate for me.

So I was spooning perchlorate into my acrolein and it kept dissolving – I ended up adding a whole lot of it and it was still dissolving and the mix was getting alarmingly hot and yellow. “Oh no, the perchlorate is all soluble and my acrolein is now polymerizing because of it, I will lose it all – quick, I must distill it all at once to rescue it!”. So I put the mix onto a heating mantle, added a distillation adapter and condenser and turned the heat on.

The hood sash was down and I was few meters away when a brilliant orange light from within the flask illuminated the lab and the entire hood turned black in an eyeblink. With a tremendous “wroooommrrr” that rattled the windows, the mix instantly burned away like a rocket engine and then the flame died out – before I realized what I have just done. The flask was still in one piece (only the condenser flew out) and a foot-high layer of soot was now filling the hood. The black tongues got painted on the wall behind the hood, emanating from the few places where the hood leaked. I turned around and saw a black cloud hanging by the ceiling and slowly settling down like a pillow. The entire  lab got dusted with the greasy soot – a notebook lifted from the bench left a light rectangle behind…

It is inconcievable how much fluffy black dust can be produced from a half-liter of this mixture – I remember scooping out several buckets of soot that I had to smuggle out of the building. About six hours later (and a bottle of detergent) I was looking like a chimney sweep but the lab was all scrubbed clean and nobody found out about my perchlorate+acrolein jet propulsion experiment.

Milling KOH: I was about to reproduce some old-fashioned procedure that used a slurry of powdered KOH in toluene as a base. Now KOH is very hygroscopic – I tried to powder it with a mortar and pestle at first and the pellets were flying all over as I pounded on it while the stuff was melting into a puddle of lye. I realized the grinding had to be done very fast. Asking around, I found out that one faculty man owned a fancy electric grinder: The machine looked like a giant coffee-grinder on a blender; the container was made of heavy glass and the oversized motor had a beautiful aluminum casing.

“It’s the only power-grinder we have – You are not going to use it on anything corrosive, right?” – the owner asked. I assured him I wouldn’t.

The grinder worked amazingly well and in no time I had lots of free-flowing KOH dust (which I immediately bottled to keep it from getting soggy) – but I noticed as I was taking the grinder apart that I spilled some KOH dust onto the motor casing and the aluminum was getting pitted by the hydroxide. More worryingly still it looked like the caustic dust has gotten into the electric motor itself through the vent holes in the casing. It gotta be cleaned promptly.

I was not familiar with the Mr. Bean skit character back then, but with the same kind of single-mindedness I proceeded to wash up the motor casing in the sink. I was not careful and some water splashed through the vent holes  – and since the KOH dust got in there and the electric motor was  already wet, I decided that the motor deserved a proper rinse as well – I would dry it afterwards. So I had the water flowing in and through the motor.

The owner of the grinder dropped by later that afternoon to find out how it worked (and if I was ready to return it). I said I needed to clean it up a bit more – the motor was still very soggy and I prefered not having to explain how it got that way.

Wet glassware dries pretty fast when rinsed with acetone. Being in hurry I reached for a squeeze-bottle and washed the motor with acetone too – and surprise – the acetone coming out from the motor was dark brown and smelling just like shellac resin that is used to insulate the fine copper winding in  electric motors…

I was horrified, I realized I just ruined it completely and I better try to cover it up. I dried the motor with a heat gun and assembled the grinder. I gave it a good final polish and then I waited patiently until I saw its owner walking away from his lab – and then I sneaked in and put the grinder back in the cabinet as if nothing bad was done to it (I turned the pitted aluminum part away from the sight). Just as I was closing the door the owner returned. “Thank you – it worked great. I put your grinder back and it’s all clean now…”

But the luck was not with me. “OK – let me see if it still works” the guy says – and he takes this thing out and plugs it in the wall. A loud bang and a green-and-white lightning, the sparks flying all across the room and rolling on the floor before gradually dying out like embers. (I saw a street transformer once, blowing up like that but from a safer distance). We were standing there in silence for few long seconds – the only sound was the “klip-klop-klop” from the hallway as the circuit breakers gave up one by one and plunged the chemistry building into darkness.
The faculty guy then turns to me and says: “Thank you. Don’t hesitate if you need my help again.”

August 5, 2008

The scent of tramp

Filed under: lab destruction — milkshake @ 1:47 pm

The grumpy old man from the preceding story (who fired me for stinking up his lab) had himself an accident in his younger years. Here is the story as told and re-told over the years:

The guy was making ethylthioester of acetic acid. While he was working up the reaction mixture and doing the extraction with ether he ineptly released the sep funnel stopcock and the over-pressure sputtered some of the mix on him with a good aim – all over his face and forehead.

So the guy immediately proceeded to wash himself with bleach and soap and alcohol but it hardly helped.  A good thing he was wearing his old working clothes with acid-eaten holes, too (but it must have made him look more like a bum rather than a young faculty). The mishap occured later in the morning on a warm day in May. There is a public bath place with the Olympic-sized swimming pool and sauna located just two tram stops away from the campus – and our guy was a frequent visitor there and he got the brilliant idea that he should go there at once and have a dip to wash off that reek in a pool of chlorinated water.

As soon as he got on a tram all fellow passengers re-positioned themselves towards the opposite end of the tram.  A little boy riding there with his mom said in a sorrowful voice: “Ma – I think this scarry man just pooped himself”.  Few faces lit up. The mom answered, stern and loud – for the benefit of everyone on the tram :”No, Johny, this man did not poop himself. He just needs soap and water – lots of soap, and lots of water.”

Our guy promptly got off at the next stop; he finished the rest on foot. The cashier and the locker room lady gave him strange looks but otherwise the place was almost deserted – it was a business day and morning time. So our guy showered himself and then was swimming back and forth, many laps in that giant pool but the stink was still with him. “No use to swim in the cold water – but volatile organics azeotrop with steam”, he though. He headed to sauna.

It was still early in the day and he had the whole sauna to himself; he was sitting there relaxed and for the first time he felt like the stink was gradually weakening until he could smell it no more. Next, the door opened and another nude dude with a towel sat on a bench across the room. He was apparently some sort of hyperactive fellow – instead of leaning back the new guy kept looking left and right. He got up and looked under the bench, then he walked across the sauna room, looked under other benches too and inspected every corner. Finally he said, perplexed: “It beats me – the shit gotta be here somewhere!”

August 2, 2008

This phosphine will get you fired

Filed under: lab destruction, lit highlights, mechanisms — milkshake @ 11:32 pm

Beautiful asymmetric transition metal-catalysed chemistry with phosphine ligands chiral on phosphorus dates back to Knowles and Mislow. But these P-stereogenic homochiral phosphines are usualy harder to make, so they were eventually supplanted by ligands with chirality on carbon. As a freshman I used to work for a young assistant prof in Prague – and since I was very interested in asymmetric synthesis, he suggested that I could do a thesis work with him on these ligands; We would put some chiral but racemic phosphine building block onto optically active binaphtyl piece derived from BINOL, and we would get BINAP-like ligands with both axial chirality and chirality on phosphorus. We would then try to separate the stereoisomers and see which one worked better in Rh and Ru-catalysed asym hydrogenations, and we would try to interconvert the stereoisomers to see how the kinetic vs thermodynamic induction control looks like, etc. (Chiral phosphines are conformationally labile on phosphorus above 100C whereas the 2,2′-disubst binaphtyl pieces are fairly stable and should not racemize).

This all happened more than 20 years ago and there is over-abundance of commercial chiral phosphines nowadays –  though as far as I know the doubly-chiral BINAP idea was never put into practice. The reason why we never managed to put it into practice was that we were inadequate – We did not realise that phosphines are so unstable. Unless in crystalline form or complexed to things like borane, alkyl phosphines oxidise rapidly in air (for example the used silica and eluent has to be deoxygenated)- and we had no glovebox; not even a vacuum/argon manifold line.

The other reason was that I got fired from that lab soon after I started working on this project. Here is the story how it happened:

My adviser was a junior faculty, at a poor university – he shared the workspace with two other faculty members. The actual boss of the lab was an old and rather sardonic man. The old man became  noticebly grouchier during the year when I was working in their lab, especially after I had couple of fires and broke every valuable piece of glassware they had there; and soon everybody was calling me the Disaster-Master and “Bořivoj” – It translates as “the one who tears down the places”. Me and my young adviser made quite an enthusiastic team – we tried to synthesize optically active binaphtyl compounds on a grand scale. And when a 4-liter flask full of xylene refluxing on your bench ruptures into the heating mantle, people start taking notice…

There is a lovely one-pot procedure for turning triphenyl phosphine into PhePHMe: Sodium metal in liquid ammonia cleaves off phenyls from the phosphines in a controllable fashion. It goes like titration – while you feed the reaction mix with chunks of Na metal, the red color of Phe2PNa develops which then suddenly turns inky blue by the dissolved metal once you reach the equivalence point with 2 equivs of Na. Then you add tBuCl to selectively quench the formed sodium amide followed by MeI, to methylate the diphenyl phosphide anion, and the red color vanishes. Then you add more sodium until inky blue again, quench with solid NH4Cl, evaporate, then distill. The literature procedure has no comments on the smell of these things; I guess a man skilled in art is supposed to know. (We did not).

An inorganic chemistry colleague actually warned us about the phosphine stink – he advised us to make these compounds at night (and preferably in a student lab), to use baths of acidified permanganate or bleach or peroxide and decontaminate everything afterwards. It seemed  excessive to me but my boss borrowed keys from the teaching lab located at the distant end of a very long hallway, and we went to work there one Spring Sunday afternoon.

The reaction behaved beautifully – exactly as in literature procedure – the color transitions and all, and even the product distilled pure in a good yield in the end as a highly refractive clear, thin liquid. But the smell – right at the moment when we quenched (in a hood of course) we were pushed back by the solidity of the reek. I got to know many evil chemical smells over the years but nothing comes anywhere close. With the other stinkers, at least one can imagine what sort of unwashed, putrid, fishy, skunky, human-waste object those smells are related to. But I never encountered anything as nauseating or alien like PhePHMe: The memory is stil with me – the most sickly and sweetish smell of rancid gasoline combined with rotten water melons, with undertones of stale sweat, pig carcass, a hint of garlic, moldy oranges, russian-made aftershave and a cheap household air freshener…  its a whole package, and rather sweet one – like isonitriles or cyclopentadiene but magnified thousand times. A whiff of that thing and you feel that your nose just suffered a stroke and will hopefully die and peal off so that you never smell that thing again. Inconceivable – and it does not get any better when wearing off; quite opposite in fact – just like with butyric or isovaleric acid, the reek is developing a more alarming depth and complexity with the dilution.

Phosphines like to oxidise on air (unless in crystalline form) and those with H or small alkyls on P tend to catch on fire when neat. There was a flame-up when I took an adapter off after the vacuum distillation from a still warm flask – a bright flame jumped through, with a high-pitched bark and yet another wave of nauseating reek crashed over us…

Finally, we sealed the product into ampules as to keep it from oxidizing. We washed all the used glassware in permanganate and then in bleach – twice – and we put it on a cart and brought it back to our lab, happily tired after a long and productive Sunday. I remeber that before heading home – as I was putting the glassware on the drying rack above the sink – I noticed a shred of glass from a broken adaptor that remained in a joint of the distillation flask. (I panicked when the thing flamed on me and I broke it). So I dislodged that piece from the joint with tweezers and thew the shred into a glass waste bin next to the sink. It was late night and I did not give it much thought; I did not realise that the broken piece was stuck in the joint and the surface between the two did not get in contact with the bleach bath.

The next day we were both late, I made it to the lab at around 10:30a before my adviser arrived – and I noticed that all windows in the lab and hallway were open. Nothing too unusual on a warm late-spring day – except that our grouchy old colleague’s face was somewhat sallow. He even seemed pleased to see me, and he welcomed me calmly: ” Please sit down, Mr. Bořivoj. It is with enormous satisfaction for me to inform you that your long tenure in this lab just came to its abrupt end. My patience has been worn thin and through. I have been doing chemistry for forty years now and I have no desire to ever puke my guts out again in my own lab on Monday morning.”

I forgot to mention – this old man spent his career on making vinyl sulfur-and-selenium compounds. Forty years – and even he was impressed with our phosphine.

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