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December 3, 2010
Going to Let Someone Else Do This One
Posted by Derek
Fluorinated compounds are always of interest to a medicinal chemist, and difluordioxolanes are perfectly reasonable things to put into a drug's structure. But any method that first uses thiophosgene (you can buy it easily, but here's a good old prep that gets across its fine qualities) and follows that up with bromine trifluoride (which shares many of the wonderful properties of its sibling). . .well, let me know how it goes, and do it far downwind of me.
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College chemistry, 1983
The 2002 Model
After 10 years of blogging. . .
1. BoredChemist on December 3, 2010 10:08 AM writes...
I know that it's more expensive than thiophosgene, but couldn't thiocarbonyl diimidazole work just as well? At least it's a solid!
Permalink to Comment2. distantdiamond on December 3, 2010 10:09 AM writes...
I loved note 3 in the thiophosgene prep.
"The vapors formed in the experiment are very objectionable."
You don't say!
Permalink to Comment3. andrewD on December 3, 2010 10:40 AM writes...
Really Derek, what is objectional about Thiophosgene? it smells like beef stock. I have made 100kg on industrial plant and would add to the Org syn method a note the acid concentration is critical in stage 1 ,if correct the Pentachlormethyl mercaptan can be used with out purification. Thiocarbonyl diimidazole is made from thiophosgene-Ive made this on plant as well.It is light,water, and air sensitive-thiophosgene is easier to use
Permalink to Comment4. A Nonny Mouse on December 3, 2010 10:51 AM writes...
Considering that Fludioxonil is currently made for about $40/kg, I should thing that this is an expensive way of going about things (I assume that's what they are trying this for).
Thiophosgene is certainly much easier to handle than phosgene or its equivalents as pointed out in post 3.
Permalink to Comment5. A Nonny Mouse on December 3, 2010 10:51 AM writes...
Considering that Fludioxonil is currently made for about $40/kg, I should thing that this is an expensive way of going about things (I assume that's what they are trying this for).
Thiophosgene is certainly much easier to handle than phosgene or its equivalents as pointed out in post 3.
Permalink to Comment6. milkshake on December 3, 2010 10:53 AM writes...
thiophosgene is OK with me, BrF3 is not. I wonder if there is some better alternative like NIS + NEt3.3HF combo, or Deoxyfluor, to bring about the desulfurative fluorination
Permalink to Comment7. BoredChemist on December 3, 2010 11:45 AM writes...
@Milkshake: Does DAST give you jitters?
Permalink to Comment8. Anon on December 3, 2010 11:47 AM writes...
Just saw this on JACS ASAP:
Discovery of 4-tert-Butyl-2,6-dimethylphenylsulfur Trifluoride as a Deoxofluorinating Agent with High Thermal Stability as Well as Unusual Resistance to Aqueous Hydrolysis, and Its Diverse Fluorination Capabilities Including Deoxofluoro-Arylsulfinylation with High Stereoselectivity
http://pubs.acs.org/doi/abs/10.1021/ja106343h
Permalink to Comment9. milkshake on December 3, 2010 12:52 PM writes...
DAST is nasty with water (thats why you dilute it down with something chlorinated before quench) and it generates lots of HF. But BrF3 actually ignites with non-chlorinated solvents, and they made their reagent in this paper by passing neat F2 over neat Br2 with chilling in a chilled copper vessel...
Permalink to Comment10. AlchemistOrganique on December 3, 2010 2:38 PM writes...
Mmm...reactive fluoride reagents. Nothing like a good old peptide cleavage from Meerifield Resin using distilled HF! Personally I not a fan of sulfur tetrafluoride.
Permalink to Comment11. Tim McDaniel on December 3, 2010 6:59 PM writes...
Given the page title, shouldn't this be categorized under "Things I Won't Work With"?
Permalink to Comment12. Ori on December 5, 2010 3:12 AM writes...
This new flourination procedure is by far more interesting and safe:
http://pubs.acs.org/doi/abs/10.1021/ja106343h
Permalink to Comment13. BoredChemist on December 5, 2010 1:46 PM writes...
@12: #8 already cited the new fluorination procedure.
How about using animal bone meal to quench fluorinating reagents? Apparently it can catalyze crossed-aldol condensations! Courtesy of "Martyn" at Totally Synthetic:
http://dx.doi.org/10.1016/j.tetlet.2010.10.056
Gotta love Tet Lett for publishing such quirky chemistry!
Permalink to Comment14. Vader on December 6, 2010 11:05 AM writes...
"Decided care should be exercised in the handling of thiophosgene because of its high toxicity."
Calls to mind:
"Okay. All right. Important safety tip. Thanks, Egon."
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