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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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December 3, 2010

Going to Let Someone Else Do This One

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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.

Comments (14) + TrackBacks (0) | Category: Chemical News


COMMENTS

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 Comment

2. 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!

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3. 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 Comment

4. 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 Comment

5. 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 Comment

6. 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 Comment

7. BoredChemist on December 3, 2010 11:45 AM writes...

@Milkshake: Does DAST give you jitters?

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8. 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 Comment

9. 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...

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10. 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 Comment

11. 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"?

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12. 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

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13. 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 Comment

14. 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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