B.R.S.M. Yield isn't everything


I’m sure glad I don’t use thiophosgene anymore

I doubt many people have used thiophosgene. Especially not as much as I have. For those that haven't experienced its penetrating odour and beautiful red colour, on balance I wouldn't recommend it. I used to use it for the second step in an (as yet unfinished) total synthesis of a natural product, to make an arylisothiocyanate, which meant using lots of it. I starting to bring more material through the route a few weeks ago and, performing the same step on 50 grams, was glad that I'd changed to using thiocarbonyl diimidazole (TCDI) the last time I had to do this. It's a pretty, bright yellow solid and far less malodorous; you can even weight it on a bench top balance (in the evenings and at weekends). It costs a bit more and isn't as reactive (my reaction takes 24 hours refluxing 1,2-DCE as opposed to a few hours at room temperature with thiophosgene), but on the upside it's not a war gas. TCDI is to thiophosgene what the ever popular carbonyl diimidazole (CDI) is to phosgene (also a war gas, but slightly better smelling).

So why bring this up? Well, today I needed to dry some carbon disulfide,[1] so I dug out the trusty lab copy of Amarego and Chai (or as most call it, and note the definite article here, 'The purifications book'). After finding the information I needed (distill it from CaH2 - who'd've guessed?) I glanced at the opposite page (always do this - you can learn a lot) and noticed that the entry for carbon tetrachloride listed the major impurity as CS2. That's a bit odd, right? I mean, they're quite different compounds. One's good for dry cleaning and global warming and the other's good mostly for eroding the inside of your face.[2]

Well, it turns out that back in the day a lot of carbon tetrachloride was produced from the reaction between CS2 and chlorine gas, via thiophosgene and trichloromethanesulfenyl chloride. In fact if you ever wanted to fall out badly with your coworkers you could even make your own thiophosgene from good old CS2 by stopping the reaction part way, and reducing down the CSCl4 intermediate with a bit of tin or sodium sulfide. You're having a bad day with Na2S is the least hazardous component in your reaction mixture. There's even an organic syntheses proceedure for the tin reduction, which somewhat redundantly points out 'the vapors formed in the experiment are very objectionable'. Don't do it. They don't pay you enough.

For a review on things you can do with thiophosgene,[3] see S. Sharma, Synthesis, 1978, 803 - 820.

[1] To quote from my supervisor's textbook on practical organic chemistry 'the use of this solvent should be avoided at all costs'. I share a lab with an inorganic group into nanotubes and fullerenes, and a postdoc of theirs used to run all his columns in carbon disulfide, claiming nothing else worked. They literally got though litres of it each day.

[2] According to the Merck index, pure carbon disulfide has a pleasant odour redolent of diethyl ether. A shame that you can't buy it pure enough to ever experience this. Even the stuff I distilled stinks. Apparently the culprits are OCS and thiols, which can be removed by washing with aq KMnO4 solution, followed by mercury. Or not.

[3] There are a few gems in here. For example, were you ever curious as to what happens when you mix thiophosgene with sodium azide and quench with dimethylamine? Me neither, but apparently 'the preparation is generally accompanied by violent detonations'.

Filed under: Lab, Serious Leave a comment
Comments (6) Trackbacks (1)
  1. Enjoyed reading the post and the rest of your blog-only found out about it from Twitter (New Reactions tweeted it)!

    I have used thiophosgene before, the odour is very unpleasant indeed. In a non-ventilating fumehood (long story) it smelt a bit like rotten cabbage and the vapours made me cry…..!

    • In a non-ventilating fumehood? That truly is terrifying! I’ve been trying to give away some excess thiophosgene that I ordered before changing to TCDI but no-one seems to want it. Maybe I should just dump a load of imidazole in it and make my own – I think I remember seeing an org. synth. prep for it a while back. I can’t believe how nice everyone is being in linking here, and how quick word spread – I told one friend with twitter on Friday that I had a blog, and suddenly I have readers!

      • I might be interested in your extra thiophosgene! Or at the least, can you tell me where you got it? I’m trying hard to source some for a pharma prep and having precious little luck. thanks! Tim (timothy.ullman@amriglobal.com )

        • Sorry, I succeeded in giving that away in end! In the UK you can get it from either Sigma-Aldrich or Fisher Scientific (I’ve successfully ordered from both). I’m not sure if it’s a controlled substance or not – been hearing mixed things. I work at a nice university where I just order things and then other people make the arrangements and they arrive, so I’m not sure how easy it is to actually get. I guess most pharmaceutical companies have a similar setup. Good luck!

  2. Oh I shall be interested in following up any preps that you share in the future. I loved the side comments on the post, favourite line: ‘…can be removed by washing with aq KMnO4 solution, followed by mercury. Or not.’
    @NatureChemistry is already loving the blog, see for yourself
    Just a suggestion you’ve probably thought of already: add a share button on the wordpress blog will aid the tweeting!

  3. Thanks! This was my attempt at a half-funny post; kind of in the style of Derek Lowe’s legendary ‘Things I Won’t Work With’. I just created a Twitter account yesterday, and I’m surprised at how much the blog’s being tweeted. As soon as I work out how I’ll add a ‘tweet this’ type button…

Leave a comment