Or: Somewhat Like Cooking
We all know what it’s like to be desperate for a reaction to work; to need a result so badly, or to have a supervisor breathing down our necks, telling us that something must be possible. I’m sure all bench chemists can remember searching the literature for a procedure to prepare a given compound, only to find one, read it and then discard it for being too dangerous or just plain ridiculous. We can all probably think of a few procedures that we're just not paid enough to follow. For example, before Christmas I wanted to make some of this carboxylic acid.
Easy, right? Surely you just oxidise the 2,5-hexadienol that you can get in one step from allyl bromide, unprotected propargyl alcohol and indium? Nope, there are numerous preparations reported, and they all use either tin, or worse, nickel tetracarbonyl. A thing that myself and Derek Lowe definitely won’t work with.
Yup, chemists love to talk about dangerous procedures. But what about ridiculous ones? I once heard an academic tell a story about his time as postdoc with Steve Ley. In his first few months in the group, another postdoc whom he referred to as ‘Crazy Norman’ had been working out the last few steps in a natural product synthesis. The final reaction was the selective reduction of one of three or four double bonds in the molecule by hydrogenation. Norman performed this reaction once on a small scale, got some NMRs and then left and moved on. After he was gone, Ley set another postdoc the task of making a little bit more of the natural product, by repeating Norman’s final step. But they couldn’t. The particular selectivity that Norman observed (and had the NMR data to prove) was never seen again. His successor tried everything – different catalysts, solvents and temperatures. New glassware, clean stirrer bars, old glassware and dirty stirrer bars. They stirred clockwise and anticlockwise, by the window and in the dark. It was rumoured that someone in the lab might have been doing some sulfur chemistry on the day when Norman did his reduction, so they tried even tried wafting some thiols at the flask full of catalyst and solvent, to maybe poison it just a little bit. Eventually, they rang up Norman to ask if he remembered doing anything – anything at all – unusual when he ran the reaction. He thought for a while and then replied, in total seriousness, “I think I might have washed the glassware with Vimto”.
Image from americansweets.co.uk
Give that man a Tet. Lett.! Here are a few other examples of ridiculous things you’ll never try:
1. Michael Additions, Catalysed by Genomic Salmon Testes
Obviously the actual catalyst is the DNA, as it says in the title of the paper. The idea of DNA as a catalyst isn't new, but I'm not sure why such an exotic source is required. I mean, isn't it in, like, everything? Initially I imagined PhD students being sent out with nets and scissors to 'acquire' fresh catalyst, but it turns out that Aldrich sells it. I still don't think I'd try this.
2. Heterocycle Synthesis Catalysed by Animal Bone Meal
“Animal bones were collected from nearby butcher shops. All of the attached meat and fat were removed and cleaned from the bones. The bones were then washed several times with tap water and left in open air for several days to get rid of odors. Later, they were transferred to the oven at 80 ºC for drying. The dried bones were crushed and milled into different particle sizes in the range 45–200 μm then calcined for 2 h at 800 ºC… The resulting material was denominated ABM. The catalysts obtained were characterized by X-ray diffraction”
The fun doesn't stop there as the ABMs don't do an awful lot until they're doped with Lewis acids such as ZnCl2 and CuCl2, but then you can use them to do all kinds of tricky transformations like the formation of 2-phenylbenzimidazoles from o-phenylenediamine and benzaldehyde.
3. Asymmetric Reductions Over Finely Divided… Carrots
From the abstract:
“Reduction of (+)-and (−)-camphorquinones (1a, 1b) by various vegetables (carrot, potato, sweet potato, apple, Japanese radish, cucumber, burdock and onion) gave α-hydroxycamphor selectively. Using burdock, (+)-camphorquinone was reduced to give (−)-3S-exo-hydroxycamphor (4a) as major product in high stereoselectivity with high yield. Moreover, 1,2-cyclohexanedione (1c) and 2-methylcyclohexanone (1d) with various vegetables afford enantiomerically pure trans- and/or cis-alcohol, respectively. Various vegetable reduction gave a new idea of a biotechnological process.”
This isn’t a process that uses isolated enzymes, or cell cultures or anything fancy. Because, as the authors assert, ‘It is known that various enzyme is included in vegetables’. You literally put some sliced carrot in a flask with your substrate and shake. I find this statement about a control experiment quite amusing:
“Furthermore, for consideration of the influence of a microbe, we tried under the sterilization condition (a carrot is sterilized with 70% ethanol and an ultraviolet lamp for 6 h). Consequently, yield and stereoselectivity did not change.”
Doesn't the thought of finding a carrot under your TLC lamp make you smile?
Many thanks to David Lindsay for bringing this to my attention!
4. Michael Additions to Nitrodienes… in Heineken
Admit it – if you had a reaction that worked great in H2O/EtOH 5% v/v you’d obviously try running it beer. I know I would. If I was refereeing this, I would definitely have suggested that a screen of different beers was carried out. Incidentally, did anyone else see that rather bizarre J. Chem. Ed. paper at the start of the year, titled ‘Beer as a Teaching Aid in the Classroom and Laboratory’? Apparently, ‘Beer was chosen as a teaching tool to maximize students’ class participation and systemize and enhance their knowledge of chemistry.’ Hmmm, okay. Still, a great abstract image:
Taken from pubs.acs.org
1. You can also get a flavour of its nastiness from the Wikipedia page:
“Its LC50 for a 30-minute exposure has been estimated at 3 ppm, and the concentration that is immediately fatal to humans would be 30 ppm. Some subjects exposed to puffs up to 5 ppm described the odour as musty or sooty, but since the compound is so exceedingly toxic its smell provides no reliable warning against a potentially fatal exposure.”
There's not enough money in the world...
2. There’s another great Crazy Norman story, where he apparently staggered into the lab late one morning, clutching a half empty bottle of Bell’s Whiskey, and claiming that the alcohol content couldn’t be what it said on the bottle as he wasn’t anywhere near drunk enough. He then proceeded to waste the entire day GC-ing and NMR-ing the whiskey to try and get some proof of this, before writing an angry letter to the manufacturers. Whoever received it must have been pretty intimidated by the (nonsensical) GC traces and Cambridge University return address as they sent him a grovelling apology along with several bottles of whiskey by way of recompense.
3. My favourite ridiculous paper of recent times has to be this absolute gem from Angewandte on fluorescence spectroscopy of bananas. These are easily the best figures I've ever seen in a chemistry research paper: