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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

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March 6, 2013

Safety Warning: Togni's Reagents

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Posted by Derek

togni%27s.pngSome of you may have used the second Togni reagent (shown) as a trifluoromethylating agent. Well, there's a new paper in Organic Process R&D that brings word that it's an explosive hazard. A group at Novasep, in Leverkusen, Germany finds that it has a powerful exothermic decomposition, and (in addition) it's about as combustible as black powder. Sensitivity to impact and friction varied from sample to sample as well, which isn't what you want to hear, either. Their conclusion is that the reagent is "dangerously explosive and may only be transported by approval of the national competent authority." The first Togni reagent (with a dimethyl in place of the carbonyl) wasn't fully evaluated, but it may be just as bad. That one has been available from Aldrich; I imagine that this may change shortly. Too bad - these are useful reagents, but not if you have to suit up to use them safely.

Comments (11) + TrackBacks (0) | Category: Safety Warnings


COMMENTS

1. Dave on March 6, 2013 2:55 PM writes...

Not too surprising. That trivalent Iodine can't be too happy, and that five membered ring should be trying to come apart. It might be interesting to see the decomposition products, just to determine how it wants to rearrange itself. It's hard for me to believe that it would be quite as explosive as black powder, but it may be close in terms of sensitivity (Black powder is a pain to work with!).

Dave

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2. Robert on March 6, 2013 3:46 PM writes...

There's also a S-trifluoromethyl dibenzothiophenium (tetrafluoroborate?) salt that seems to be used in electrophilic trifluoromethylation papers as well. The dibenzothiophene byproduct might be too heavy to stink strongly, but I don't know.

I guess it's a natural consequence of trying to make an electrophile out of something that really doesn't want to be one, but it seems like the electrophilic trifluoromethylating reagents involve reagents roughly the size and weight of a barn door.

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3. Andrew (@_byronmiller) on March 6, 2013 5:54 PM writes...

This is a newbie question: if these have been used widely, how come this is only just coming to light?

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4. Anonymous on March 7, 2013 7:31 AM writes...

#3 because this is how we learn about them. They are widespread enough that people think about using them at large scale and hence perform feasibility studies. None of this matters when working with a few mg of the stuff.

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5. curious on March 7, 2013 8:13 AM writes...

What is Black powder?

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6. Okie Chemist on March 7, 2013 9:58 AM writes...

Curious - "Black Powder" = Gunpowder.

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7. Anon on March 7, 2013 9:58 AM writes...

Black Powder is the original explosive used to make guns and cannon go boom... a mixture of mostly potassium nitrate, charcoal, and sulfur

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8. Mike P on March 7, 2013 11:46 AM writes...

If these have been used widely, how come this is only just coming to light?

Black powder can be safely handled by pouring, weighing, etc. Chemists don't handle Togni's Reagent any more roughly than that.

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9. Patrick Eisenberger on March 7, 2013 12:28 PM writes...

We used to refer to this method of trifluoromethylation as "fluorine chemistry for sissies", since you did not require harsh, corrosive fluorinating reagents. It seems this is no longer the case. But hey, DMP (and its precursor IBX) makes a pretty nice bang and is used routinely in organic chemistry. These things are called reagents for a reason: they are designed to be reactive.

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10. Real issue? on March 10, 2013 12:14 PM writes...

The tests as described in the Organic Process R&D paper are carried out routinely in any professional process chemistry setup nowadays. Furthermore, the results are not a big surprise. The issue is not as dramatic as to become the subject of a major discussion.
Obviously, these compounds need some attention when it comes to their safety on scale. But based on a detailed evaluation in a risk assessment they may be used safely with appropriate measures in place.

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11. Anonymous on November 25, 2013 7:30 PM writes...

Wow, I'd been using the hell out of this on a (shelved for now) alkane trifluoromethylation project about a year ago. It never went off on me of course, and from what it sounds like it doesn't seem so bad, just should come with a warning for being potentially explosive.

I hope it's not harder to get if I get back on that...

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