And Now For Something Completely Different 6: Green Chemistry
Most of the credit for this one goes to occasional commenter Martyn!
Is it just me, or will green chemistry journals publish anything these days? For example, check out this paper published this morning in the Journal of Sustainable Agitation:
Unpowered Mechanical Stirring of Reaction Media Using Renewable Stirring Fish (RSFs). [PDF]
I couldn't make this stuff up!
And Now For Something Completely Different 5: The Merck Index Challenge
Sorry things have been so quiet around here; it's been a hectic month! Here's something silly born of an unusual conversation over coffee.
The office microwave: unnecessary chemophobia?
The Merck Index, along with Fieser and Fieser's Reagents for Organic Synthesis, Greene’s Protective Groups, March’s Advanced Organic Chemistry and Amarego’s Purification of Laboratory Chemicals is one of those books that any self-respecting organic research group will have a copy of. It’s an iconic reference work, although its usefulness has definitely waned in recent decades with the rise of the internet, Scifinder/Reaxys/Chemspider and Wikipedia. As Derek reported before Christmas, it was recently acquired by the RSC, who have just released an updated edition. I mostly use mine to pass the time waiting for NMRs to run, or when I need a more reputable reference than Wikipedia for a paper or report.[1] However, all of that changed last week when a tea break conversation sparked a bizarre new game: The Merck Index Challenge.
Anyone who’s ever flicked through a copy will probably have noticed that amongst all the drugs, solvents, salts and plants there are a number of… aberrant… entries. For example, Whiskey. And Lard.[2] And Raspberries. And Quorn. And Milk. Thus, the question arose: could a meal be constructed using only ingredients from the Merck Index? Better yet, could one manage three courses?
Who Ya Gonna Call? Blog Syn!
Ever see a reaction in the literature and think, "that seems a little too good to be true..."? Retro Baeyer-Villiger reaction? Quantitative cleavage of methyl ethers with Amberlyst-15? Catalytic reduction of alcohols to hydrocarbons with Dess-Martin? Bring it on! Ever struggle with a sensitive or fiddly reaction and wonder, "is it just me? Should this work?"? Well, now you don't have to! Thanks to a collaborative new website brought to you by See Arr Oh, with a little help from Organometallica, Mat Katcher and Myself. Now, if you find a reaction you can't reproduce or don't believe, simply head over to Blog Syn, and let us know.[1] Alternatively, if you think you'd like to be part of helping to make the literature a little bit more reproducible, pay us a visit and see what needs checking! If we all just run a few extra reactions a year we should be able to save chemists around the world many wasted hours and much frustration. You might even have some fun, make some new friends, and perhaps even learn some chemistry besides!
1. Or email See Arr Oh or myself
An Uncommon Lab Reference
Last Monday I set my MSci student the task of preparing the above compound and sent him off to do some literature searching. He quickly found a mention of it in a J. Med. Chem. paper, although the authors didn't give any detail themselves on its preparation, instead claiming to have used the method of Shulgin and Shulgin, described in reference 17:
That's right: a reference to PIHKHAL in the primary chemical literature! When I got over my initial surprise I did track down a copy (the university library didn't have it) to look up the procedure. Indeed, a very detailed and reasonable sounding synthesis of the compound is described under the chapter on the synthesis of 2C-T-2 (along with an evocative description of just how high you can get on it).[1]
There's lots of detail and the whole thing is done on sufficient scale to produce 10 grams of the desired compound. Perhaps not too surprisingly, the route starts with chlorosulfonation of 1,4-dimethoxybenzene, followed up with reduction (Zn in HCl) to give the thiophenol which is then ethylated. Easy. We're going to try it this week, and I will enjoy seeing PIHKAL referenced in a lab notebook. It's funny, I've been aware of this book for probably ten years or more - heck, I even gave a talk last year entitled 'Quinones I Have Known And Loved' - but I never thought I'd be reading it at work. Steven Weinreb once said of Russell Marker: "There are more stories told about [him] than any other chemist. Although perhaps many of these stories are apocryphal, they are so fascinating that more of us cannot bear to stop repeating them... they are the campfire stories that bind our profession together",[2] but I think that the same could also easily be said of Shulgin. I mean, along with Humphry Osmond the man actually coined the term 'psychedelic'.[3] I learned today that there's even a Shulgin Index, written in the style of the more common Merck index, describing the physical and pharmacological properties of some of the psychedelics he and others prepared over the years. I hope to one day have the chance to read a copy.
Etc
1. More in this vein can be enjoyed in the digitised versions of Shulgin's lab notebooks. Although his handwriting, combined with the quality lost from storage and scanning, can make them quite hard to read in places they seem to be quite interesting and frequently amusing and insightful. Although the first entry in the first book describes his experiences of taking 400 mgs of mescaline sulfate and the results (which, including hallucinations experienced with eyes open and shut were 'very pleasant'), there's also some real explorative medicinal chemistry documented there. They're actually much better kept than the lab books of many PhD chemists I have worked with, and it's easy to forget that this work was largely conducted in a shed in California. If it wasn't, you know, for all the drug taking.
2. Chem. Eng. News, 1999, 77, 78; If you don't have access to that the article was also reprinted verbatim in The Journal of The Mexican Society the same year and can be enjoyed for free here.
3. It's interesting to note that this term come from the Greek for 'mind manifesting', which I think speaks of the pair's optimism for the curative power of such compounds. Hopefully I'll do another post on chemical etymology one day.
Superlatives 1: The Heaviest Catalyst Ever?
While browsing through the Advanced Synthesis and Catalysis Early View today, I noticed this paper on a new Rhodium catalyst for the asymmetric conjugate addition of boronic acids to enones in water. Pretty standard stuff... until you look at the catalyst structure. Now, I'm not particularly up on phosphine ligand design but I don't think that PEG and geranyl geranyl geranyl geranyl geranyl chains are a common thing to include. I mean, I've seen BINAP derivatives with some pretty big polyaromatic hydocarbon groups bolted on (e.g. anthracene and pyrene), but this is in a class of its own. In fact, I think that I can safely say that this is the largest catalyst for anything that I've ever seen. I guess the logic is that if you can't have the organic solvent in the flask you can just include it in the catalyst itself by larding it with hydrocarbon and polyether chains, and it does actually seem to work. A possible drawback of this approach is that the darn thing weighs more than maitotoxin and takes a total of twelve steps to make; all that just so we can have another way to add phenylboronic acid to cyclohexenone. I'm making a note of this for the next time someone calls my total synthesis project useless. Or am I being too harsh?
Holiday!
Not that it'll be particularly noticeable, but I'm on holiday from tomorrow onwards as I take my mountain bike over to the French alps for an exciting week of trying not to break anything that'll prevent me from working in a lab. In the meantime, please enjoy this extract from our old lab copy of "Purification of Laboratory Chemicals":
The urea can then be coughed up, and then purified as described on page 355. All in a day's work.
Note: It seems that this particular 'remedy' is missing from 2003 and later editions, probably for fear of lawsuits.
And Now For Something Completely Different 4: Wikipedia Fun
Have you ever tried to look up famous chemists on Wikipedia only to end up misspelling their name or finding a more famous person who shares it? Although sometimes this can be frustrating, it can also be pretty funny.[1] Here are a few amusing namesakes I discovered recently:
As well as being one of the leading figures in the organocatalytic revolution, according to wikipedia.org, "David McMillan is a British-Australian drug smuggler who is best known for being the only Westerner on record as having successfully escaped Bangkok's Klong Prem prison". A man of many talents. Apparently, Dave avoided recapture by his immediate acquisition of an umbrella once outside the prison walls... because escaped prisoners never carry umbrellas. Clearly a clever man.
2. Phil Baron
The real Phil Baran. Credit: Sexy Science
Although he tends to make the rest of us look bad and just won't stop writing review after review after review, I still get excited whenever he publishes something. Apart from all that chemistry and reviewing, I have just learned from the Phil Baron wikipedia page that he's also a "voice actor, puppeteer and songwriter who voiced Piglet in the Disney Channel live-action/puppet television series Welcome to Pooh Corner". Where does he find the time?
Selenium: Include Me Out
No, thanks.
This week I noticed that J. Derek Woollins, head of Chemistry at the University of Saint Andrews and legendary selenium chemist, recently published a review of the research leading to the discovery of his eponymous reagent in Synlett. Although, for reasons of self preservation, I tend to lose interest in the chalcogens after the first row or two, I quite like personal accounts of research so I thought I’d give it a try. Unfortunately, being an organic chemist, I couldn't follow a lot of the inorganic chemistry but I did enjoy some of the stories of things going wrong:
“Paul Kelly also later extended this work by making M–Se–N complexes using tetraselenium tetranitride (Se4N4) as the starting material. This is a very sensitive material. Indeed the first time we prepared it (from a reaction in liquid ammonia), whilst washing the red solid with a solution of potassium cyanide, nitrogen was let into the flask fairly briskly. The resulting turbulence caused an explosion, which destroyed the flask embedding pieces of red selenium into the white shirt Paul was wearing; from a distance this looked like major bleeding. Bravery was not lacking in the group during that era, and Paul Kelly also carried out what remains as the only published reaction of (extraordinarily explosive) pentasulfur hexanitride (S5N6) to give a complex containing the [S2N3]– ligand.”
Ah, wacky fun! I’m quite sure that S5N6 falls into the category of things that shouldn’t really exist, and trying to force them to do so isn’t good for anyone’s nerves.[1] Actually, the group engaged in quite a lot of this kind of lunatic chemistry. Another great example:
“Leaning on our previous work on reactions in liquid ammonia, we prepared sodium selenide (Na2Se) by the simple reduction of selenium with sodium in liquid ammonia. The resulting material is much more soluble than that prepared by the solid state route, though it is worth noting that this wonderfully finely divided solid is also very pyrophoric – on one occasion, around 75 grams caught fire in the port of our glove box with rather unpleasant consequences.”
I imagine that ‘rather unpleasant’ probably doesn’t cover it. I can think of few things that would evacuate a building faster than screaming the words ‘selenium fire!’.[2] Fortunately, my own experience of selenium is a lot less exciting - I used phenylselenyl bromide a bit during my Masters to make enones, and aside from a marked decrease in affection from my girlfriend at the time, I suffered few ill effects. In fact, I suspect that beyond the old trick for forming enones (and the related Grieco olefination), many organic chemists would struggle to even think of uses for selenium in the lab. I am aware of one more reaction you can do with it, though, and I'll quickly explain why you shouldn't bother.
A Belated Happy Birthday To KCN
Sorry this is quite late; real life and chemistry have been kicking my ass the past couple of weeks. Hopefully normal service, and more actual science, will resume shortly.
From Angew. Chem. Int. Ed., 2002, 41, 2678
The CP molecules are scary!
Without further ado, here is a roundup of my favourite colouring competition entries. In the end I didn't get that many, despite lots of people telling me this was a great idea. Most of the contributers have already posted their entries on their own blogs, so if you keep up with other chemistry blogs (and you should, because there are some that are much better than this one) you've probably seen these already. So, in chronological order:
A New Coupling Agent, And Sandmeyer’s Other Reaction
I wrote this post a couple of weeks back, but wasn't happy with how rambling it was. Anyway, it's only getting more out of date, so I'm putting it up now. Someone might learn something.
I’ve always had a soft spot for hypervalent iodine reagents, especially iodine(III). In fact, they were the cornerstone of a methodology project that I worked on last year. You can imagine, then, that the rather usual looking iodosobenzene derivative above, which was published in Org. Lett. a couple of weeks back (DOI: 10.1021/ol301085v), immediately caught my eye. Such compounds tend to be very useful oxidants, and you can check out a few recent applications on the relevant organic-chemistry.com page. Surprisingly, though, this wonderful new reagent wasn’t being touted as an oxidant (although I’m sure it is)… apparently, it’s a great new coupling agent!