Last week we reported the discovery by customer synthesis firm Novasep that Togni II – a chemical used to add trifluoromethyl groups to intermediates in drug production – is explosive and as inflammable as gunpowder.
The finding – detailed in the March edition of the journal Organic Process R&D and a subsequent press release issued by Novasep to inform warn manufacturers of the risk.– prompted the implementation of new transport regulations for Togni II.
It also made us wonder – given that Novasep only carried out its research after one of its customers sought to scale up a production project - if any other chemicals used in drug manufacturing would be found to be explosive if test.
And the answer according to Antonio Togni – professor of organometallic chemistry at ETH Zurich and inventor of the Togni II reagent – is yes.
Prof Togni told in-pharmatechnologist.com that: “There are probably hundreds of compounds out there fulfilling such criteria, but that have never been subjected to corresponding tests.”
He also said while publicizing Togni II’s risks is important “Novasep's findings are neither fundamentally new nor surprising” adding that it is well documented that hypervalent iodine compounds decompose exothermally, thereby representing a potential danger.
“Information about safety and safety regulations are ok, as long as they don't degenerate into hype and they don't hamper sensible, responsible and necessary chemical work.
“More important, however, is that every person working in a lab knows very much in general what he or she is doing at every stage involving the manipulation of any potentially dangerous compound.”
And it looks like drugmakers will have to keep the risks posed by Togni II in mind as – according to Prof Togni – while alternatives are available they do not have precisely compartable characteristics.
“One likely alternative to our reagents for electrophilic trifluoromethylation are the so-called Umemoto's reagents, based on sulfonium salts. In comparison to the hypervalent iodine compounds, however, their application scope doesn't appear to be so broad.
“The ideal solution would be to use trifluoromethane as the primary source of any CF3 group in organic molecules, but this is still in need of a considerable research effort.”