This is a good video idea! I’d like to see this too but with the addition of what that old reaction has been replaced with in terms of modern reactions.
Here is a possible mechanism for the formation of benzoyl fluoride from phenacyl bromide, trifluoromethoxide and AgF: deptotonation of the phenacyl bromide by fluoride and acylation of the enolate with carbonyl fluoride (from the trifluoromethoxide) giving a beta-ketoacyl fluoride; attack of fluoride on the benzoyl carbonyl and cleavage of the C-C bond to yield the benzoyl fluoride and the enolate of bromoacetyl fluoride.
This is perfect! Welcome to the Journal of UA-cam. Author: That Chemist. Editorial Board: That Chemist. Peer-Reviewer: That Chemist. Impact Factor: Infinity as you’ll reach a global audience. Lol
What was the yield of the benzoyl fluoride? I can imagine under the conditions losing the carbon by a mechanism similar to the formation of bromoform, with the bromoform group finally being displaced by fluorine, You would need three bromines to do this however, so I can't see the yield of benzoyl fluoride exceeding 33%.
In reaction 2, would it be possible to displace the triflate with a strong nucleophile to make di-fluoro benzyl ethers? I can see those being useful for making reduction-stable long term protecting groups.
@@That_Chemist ah, that makes sense. I do carbohydrate chemistry, so I’m always on the lookout for potential new protecting groups. But on that note, do you have any idea if a di-fluoro-benzylether would be more stable to reducing conditions?
Accidents lead to many great discoveries: Two UW grad students tried making Alphaprodine and "self tested". They were found 2 days later, stiff and only eyelids funtioning. They had made MPTP, creating a great advance in Parkinson's disease research.
My chemistry knowledge is terrible, but for reaction 4, maybe: - coordinate some silver BF4 with acetophenone - react some bromide off via SN2 as predicted - make a little bit of photosensitive AgBr @ coordinated silver - photolyze AgBr with ambient room light - ??? - using alpha hydrogens, generate HBr (which can then form more AgBr) and (with more substitution of nucleophile) n+1 nucleophilo acetophenone, repeat until you can do haloform-esque reactions - idk wtf happens to the silver (0) this would form lol, as far as I can see this would be the terminal oxidant and that silver would have to go somewhere The silver BF4 in acetonitrile isn't a good oxidizer otherwise and something has to pick off all of the hydrogens. If it has to do with neutral halogen species being formed somewhere, it makes sense that the iodine version is worse at oxidizing alpha hydrogens and thus worse at forming the haloform products It could be neat to see if the same reaction occurs if you run it in the dark (or, if you already ran it dark, this of course torpedoes the theory). Feel free to tear this idea up in comments.
For the acyl fluoride synthesis, could it be possible a ketene intermediate is being generated in situ? Tends to be a fairly common intermediate in homologations about carbonyls.
Whaf if reaction iodoacetophenone gives slightly different ratio of products because atomic radius of iodine and bromine are different? I feel like my knowledge of chemistry is scarce in this case, but what I know is literally the first thing you are told when learning about periodicity: atomic and ionic radii of halogens are different, therefore haloorganic compounds and halogen salts may undergo different reactions/dissociate better or worse etc
In reaction 4 it might be posible that your sm forms quartic intermediate, wich then eliminates [BF3CH2Br]- , i think it might be possible as that is five membered cyclic intermediate (-B-F-C-C-Br-) wich makes that process easier
You are blessed to work on those wonderdul molecules. I'm not a great chimist but i try an hypothesis easy to prove for you: Those molecule realy looks like cccp cyanide and npe nitrophenyl caged proton, an hypothesis from my few experiment would be that those cycle pull on electron of chlore and fluor that always have at least have one non bondong pair of electron that can imply they are doniror of hydrogen bond. Even in a medium with nonhydrogen they lose their electron pair and so pull super hard on medium ro get one back. Light make the hydrogen bond wave a bit so it break and an hydrogen that is not in the plane is ejected. You could check if a 15 mM good's protonable buffer solution + 15 mM of one of these chemical that is a bit hydrophilic; exposed to uv light 20 min have a more acidic pH by nmr or fluorimetry (no ph probe it wont work). Hope its not stupid, best
As others have already suggested, as the starting point haloform reaction mechanism is highly appealing en.wikipedia.org/wiki/Haloform_reaction#Applications . Usual product in that case is carboxylic acid and haloform, but considering that instead of hydroxide you deal with F- you end up with benzoyl fluoride. For the haloform mechanism to work I would assume formation of HCF2Br, HC(OCF3)2Br or similar products through the intermediates PhC(O)CH(Br)Ag and PhC(O)C(Br)(OCF3)Ag. The oxidizing reagent in this case could (?) be Ag(1) transforming into Ag(0) through the homolysis of C-Ag bond.
Different forms of analysis - we use one type of measurement called NMR to see what types of Hydrogens we have in our sample, but this also works for other elements like carbon and fluorine. We can also do something called mass spectrometry which tells us what molecular masses we have in our sample. These two tools are often enough, but sometimes we have to use other techniques. If you can get a crystal of a compound, you can unambiguously determine what that compound is by X-ray crystallography
"So this is where I publish this."
What's the Impact Factor of a UA-cam video?
Probably gets way more views than most papers
They legit do - most of my videos get more views in a day than papers get in a year
It's possible the number of scientists and engineers of any description is also greater.
I thought the same thing! @That Chemist , can we submit our unpublished and weird results to your channel? 🤔
I'm not a chemist so everything on this channel is surprising to me
I'd like a video on reactions that have been phased out, ie, were very common before, now not so much
This is a great idea
This is a good video idea! I’d like to see this too but with the addition of what that old reaction has been replaced with in terms of modern reactions.
I'm really shocked by that last one. Never would have predicted that
Here is a possible mechanism for the formation of benzoyl fluoride from phenacyl bromide, trifluoromethoxide and AgF: deptotonation of the phenacyl bromide by fluoride and acylation of the enolate with carbonyl fluoride (from the trifluoromethoxide) giving a beta-ketoacyl fluoride; attack of fluoride on the benzoyl carbonyl and cleavage of the C-C bond to yield the benzoyl fluoride and the enolate of bromoacetyl fluoride.
interesting theory - it would cool to see someone do a mechanistic investigation paper!
nice
Chemist, T. Formation of Difluorobenzyl triflates. J. UA-cam Chem. 2022.
This is perfect! Welcome to the Journal of UA-cam. Author: That Chemist. Editorial Board: That Chemist. Peer-Reviewer: That Chemist. Impact Factor: Infinity as you’ll reach a global audience. Lol
Can you do five more :v. I really like this video
Question: at 3:24 why can't it proceed by SN2 by F- at the S carbon displacing Ag2S, removing the need for a carbocation to be made?
oh, we did trapping experiments in other work to show a carbocation was formed
1:18 explain that lewis thing please
HSAB (hard-soft acid-base theory)
@@That_Chemist oh that's cool they have affinity one is ionic other covalent
could you do a video about (tri)thioacetone? maybe also how to synthesize it
I’m sure someone in the Mayr group would be interested in the reaction rate of that nucleophilic attack by diethyl ether
didn't know anything about Fries rearrangement and this shi beautiful
:)
What was the yield of the benzoyl fluoride? I can imagine under the conditions losing the carbon by a mechanism similar to the formation of bromoform, with the bromoform group finally being displaced by fluorine, You would need three bromines to do this however, so I can't see the yield of benzoyl fluoride exceeding 33%.
It was high - somewhere between 40-60%
@@That_Chemist is there another electrophile in the reaction mixture?
I subscribed last week asking why and now I know why: that chemist works with fluorine compounds!
Scary stuff *will* happen and legends will be told.
In reaction 2, would it be possible to displace the triflate with a strong nucleophile to make di-fluoro benzyl ethers? I can see those being useful for making reduction-stable long term protecting groups.
its possible, however CF2-LG groups are really deactivated (i.e. unwilling to do SN2) - you would be better off doing cross-coupling chemistry IMO
@@That_Chemist ah, that makes sense. I do carbohydrate chemistry, so I’m always on the lookout for potential new protecting groups. But on that note, do you have any idea if a di-fluoro-benzylether would be more stable to reducing conditions?
Accidents lead to many great discoveries: Two UW grad students tried making Alphaprodine and "self tested". They were found 2 days later, stiff and only eyelids funtioning. They had made MPTP, creating a great advance in Parkinson's disease research.
Story on wikipedia. Their story sounds like your "dry lab" articles. They didn't die (not immediately) so no darwin award.
chemical model of alphaprodine looks like it would easily eliminate, and it did a bit above melting point.
interesting
My chemistry knowledge is terrible, but for reaction 4, maybe:
- coordinate some silver BF4 with acetophenone
- react some bromide off via SN2 as predicted
- make a little bit of photosensitive AgBr @ coordinated silver
- photolyze AgBr with ambient room light
- ???
- using alpha hydrogens, generate HBr (which can then form more AgBr) and (with more substitution of nucleophile) n+1 nucleophilo acetophenone, repeat until you can do haloform-esque reactions
- idk wtf happens to the silver (0) this would form lol, as far as I can see this would be the terminal oxidant and that silver would have to go somewhere
The silver BF4 in acetonitrile isn't a good oxidizer otherwise and something has to pick off all of the hydrogens. If it has to do with neutral halogen species being formed somewhere, it makes sense that the iodine version is worse at oxidizing alpha hydrogens and thus worse at forming the haloform products
It could be neat to see if the same reaction occurs if you run it in the dark (or, if you already ran it dark, this of course torpedoes the theory).
Feel free to tear this idea up in comments.
Does reaction 4 happen with chlorine too?
I really liked the last reaction. Also, how would a fries rearrangement occur on PET if the carbonyl is on the aromatic ring, not the ethylene?
Actually you raise a good point - I meant polycarbonate
@@That_Chemist Thanks for clarifying, that makes a lot more sense.
For the acyl fluoride synthesis, could it be possible a ketene intermediate is being generated in situ? Tends to be a fairly common intermediate in homologations about carbonyls.
its definitely not PhCH2C(O)F, its definitely PhC(O)F
@@That_Chemist Counting to two hard without coffee, my bad
Whaf if reaction iodoacetophenone gives slightly different ratio of products because atomic radius of iodine and bromine are different?
I feel like my knowledge of chemistry is scarce in this case, but what I know is literally the first thing you are told when learning about periodicity: atomic and ionic radii of halogens are different, therefore haloorganic compounds and halogen salts may undergo different reactions/dissociate better or worse etc
I think it’s something like a retro Corey-Chaycovsky
@@That_Chemist thank you man.helped me to discover Johnson Cory Chaykovsky reaction, and the retro exploitation! 😎
In reaction 4 it might be posible that your sm forms quartic intermediate, wich then eliminates [BF3CH2Br]- , i think it might be possible as that is five membered cyclic intermediate (-B-F-C-C-Br-) wich makes that process easier
interesting theory - it would cool to see someone do a mechanistic investigation paper!
Interested in trifluoromethoxide decomposition to F- and how it is a better F- source than fluoride. Any papers on this?
their salts are *really* soluble - trifluoromethoxide is a garbage nucleophile, and it really easily decomposes into fluoride and fluorophosgene
like if it's in solution, its decomposition is slow, but if you have any H-bond donor or Lewis acid at all, it will rapidly decompose
in the solid state, quaternary ammonium trifluoromethoxide salts are stable indefinitely
@@That_Chemist thanks for reply. Interesting molecule. Org Lett 2020 paper is nice work.
You are blessed to work on those wonderdul molecules.
I'm not a great chimist but i try an hypothesis easy to prove for you:
Those molecule realy looks like cccp cyanide and npe nitrophenyl caged proton, an hypothesis from my few experiment would be that those cycle pull on electron of chlore and fluor that always have at least have one non bondong pair of electron that can imply they are doniror of hydrogen bond. Even in a medium with nonhydrogen they lose their electron pair and so pull super hard on medium ro get one back.
Light make the hydrogen bond wave a bit so it break and an hydrogen that is not in the plane is ejected.
You could check if a 15 mM good's protonable buffer solution + 15 mM of one of these chemical that is a bit hydrophilic; exposed to uv light 20 min have a more acidic pH by nmr or fluorimetry (no ph probe it wont work).
Hope its not stupid, best
Since you do fluoro and thiochemistry, ever worked with (CF3)2CS?
Unfortunately no - it tends to form polymers tho
@@That_Chemist I mentioned it because of your blue chemistry video and remembered it is also a blue gas
As others have already suggested, as the starting point haloform reaction mechanism is highly appealing en.wikipedia.org/wiki/Haloform_reaction#Applications . Usual product in that case is carboxylic acid and haloform, but considering that instead of hydroxide you deal with F- you end up with benzoyl fluoride. For the haloform mechanism to work I would assume formation of HCF2Br, HC(OCF3)2Br or similar products through the intermediates PhC(O)CH(Br)Ag and PhC(O)C(Br)(OCF3)Ag. The oxidizing reagent in this case could (?) be Ag(1) transforming into Ag(0) through the homolysis of C-Ag bond.
It would be cool if someone did a paper on the mechanism
Umm how do you know what you form if you can’t see the molecules
Different forms of analysis - we use one type of measurement called NMR to see what types of Hydrogens we have in our sample, but this also works for other elements like carbon and fluorine. We can also do something called mass spectrometry which tells us what molecular masses we have in our sample. These two tools are often enough, but sometimes we have to use other techniques. If you can get a crystal of a compound, you can unambiguously determine what that compound is by X-ray crystallography
Wish u reach 100k
thank you for your viewership :)
recently, I observed a nucleophile Et2O on carbocation
Greetings from Germany again!
Welcome!
Maybe the mechanism of Benzoyl Fluoride formation was somewhat similar to a haloform reaction...
I hope someone eventually does a mechanistic investigation
Are all the episodes special in their own way or was this one dropped on it's head as a child?
Haha
Wait are you canadian? This "about" sounds suspicious, lol
YES
@@That_Chemist cool! Greetings from Russia. My whole lab watches your videos on the break.
If you have a reaction with really low yield, coipublish with Figuroa. (kiddin) - or just turn it over to him.