Chemi Pharma
Hazard to Others
Posts: 349
Registered: 5-5-2016
Location: Latin America
Member Is Offline
Mood: Quarantined
|
|
Fluorinating the benzene ring
Hi everybody.
Does anyone here knows about an OTC procedure to exchange the Halogen like Cl, BR or I attached to a benzene ring for fluorine?
This reaction is called HALEX REACTION, but searching at Sciencemadness, other foruns and the Web I can't find any OTC way to do this. Just complex
procedures.
Any help? preferably with support papers. Thanks.
[Edited on 4-10-2017 by Chemi Pharma]
|
|
|
woelen
Super Administrator
Posts: 7976
Registered: 20-8-2005
Location: Netherlands
Member Is Offline
Mood: interested
|
|
Then apparently this is a complex procedure. Fluorinating organics differs a lot of chlorinating or brominating things. You need completely different
reagents and conditions.
Show us what you've found so far, give concise descriptions of the procedures. Maybe others then will jump in. Just asking such a question without
showing any results or any effort does not invite people to help you. It may be considered a spoonfeeding request.
|
|
|
Chemi Pharma
Hazard to Others
Posts: 349
Registered: 5-5-2016
Location: Latin America
Member Is Offline
Mood: Quarantined
|
|
Quote: Originally posted by woelen  | | Show us what you've found so far, give concise descriptions of the procedures. Maybe others then will jump in. Just asking such a question without
showing any results or any effort does not invite people to help you. It may be considered a spoonfeeding request. |
Ok. Let's go!
I have a paper that claims nitrohalobenzenes undergoes fluorination with alkali fluorides like sodium, potassium and cesium fluorides with a
reasonable yield (attached below-FLUONITROBENZENES.Pdf). But the reaction tube must be sealed under vacuum at 290ºC for 24 hours. This procedure
doesn't work with unactivated aryl halides. This is my case.
Other paper brings the need of use antimony trifluorodichloride to do the HALEX reaction, made in situ by reacting antimony trifluoride with chlorine,
the first it's not exactly an OTC reagent (attached below-fluorination of aromatic halogenated - SbF3.pdf).
The last paper I have claims that HALEX reactions can be done with aryl halogenate and alkaline or ammonium fluoride, but demand the use of a catalyst
made by the reaction of PCL5 with dialkylamines, what is not exactly true OTC (attached below-fluorination of aromatic halogenated - Halex
Reaction.pdf).
I don't believe there's no way to do this exchange with alkaline or ammonium fluorides with no catalyser or, at least, something more OTC.
I'm sure I had a paper telling this, but i lost it in the last ramsonware attack I suffered.
Anyone can give any help?
Attachment: FLUORONITROBENZENES.pdf (229kB)
This file has been downloaded 345 times
Attachment: fluorination of aromatic halogenated - Halex Reaction.pdf (1.2MB)
This file has been downloaded 447 times
Attachment: fluorination of aromatic halogenated - SbF3.pdf (203kB)
This file has been downloaded 321 times
|
|
|
Texium
Administrator
Posts: 4508
Registered: 11-1-2014
Location: Salt Lake City
Member Is Offline
Mood: PhD candidate!
|
|
If you could make the corresponding aniline of the compound you're trying to make, you could potentially use the Balz-Schiemann reaction, which is
essentially a variant of the Sandmeyer reaction. It uses tetrafluoroboric acid as the fluorinating agent, which can be prepared in situ from boric
acid and aqueous HF.
https://en.wikipedia.org/wiki/Balz%E2%80%93Schiemann_reactio...
https://en.wikipedia.org/wiki/Fluoroboric_acid
|
|
|
Chemi Pharma
Hazard to Others
Posts: 349
Registered: 5-5-2016
Location: Latin America
Member Is Offline
Mood: Quarantined
|
|
Great help zts16.
It's just the paper I had missed. Now I remember (Fluorobenzene):
http://orgsyn.org/demo.aspx?prep=cv2p0295
Sure, sandmeyer reaction with fluoboric acid, which is an OTC reagent.
Very grateful!
|
|
|
Heavy Walter
Hazard to Others
Posts: 127
Registered: 17-12-2015
Location: Argentina
Member Is Offline
Mood: No Mood
|
|
Hi Chemi
Do you know this reference?
Attachment: Sintesis de Organo_F_Review-main.pdf (5.8MB)
This file has been downloaded 485 times
|
|
|
Chemi Pharma
Hazard to Others
Posts: 349
Registered: 5-5-2016
Location: Latin America
Member Is Offline
Mood: Quarantined
|
|
Thanks Heavy for the reference.
However the study tells more about polyfluorinated aromatics, which is not my case, it brings interesting knowledge about substitution reactions
involving fluorinated compounds.
|
|
|
Boffis
International Hazard
Posts: 1836
Registered: 1-5-2011
Member Is Offline
Mood: No Mood
|
|
@Chemi Pharma There is a paper in the JACS that describes the use of KF and various polar organic solvents such as nitrobenzene, Dimethylsulphoxide
DMSO, Dimethylformamide DMF, etc without the phosphinium salts as catalyst (ref 1).
Interestingly the very next paper (ref 2) is about the formation of aromatic fluoro compounds from amine via diazonium fluoroborates or
fluorophosphate but without isolation of the solid diazonium salt (as per the procedure in Vogel. Ref 3 and Org Synth. Ref 4) using aqueous acetone as
the medium with cuprous chloride as the catalyst.
Ref 1: JACS; 1956, v78, iss23, p6034 ja01604a022
Ref 2: JACS; 1956, v78, iss23, p6038 ja01604a023
Ref 3: Vogel, Practical Organic Chemistry 5th ed, 939 (fluorobenzene)
Ref 4: Org Synth., Col Vol 5 p133
Attachment: CV5P0133.pdf (322kB)
This file has been downloaded 374 times
|
|
|
CuReUS
National Hazard
Posts: 928
Registered: 9-9-2014
Member Is Offline
Mood: No Mood
|
|
https://en.wikipedia.org/wiki/Aryne
from chlorobenzene -http://www.freepatentsonline.com/y2005/0096489.html
[Edited on 5-10-2017 by CuReUS]
|
|
|
Boffis
International Hazard
Posts: 1836
Registered: 1-5-2011
Member Is Offline
Mood: No Mood
|
|
While looking through the references above I see that 2,4-dinitro-fluorobenzene is prepared by halogen exchange but could it also be prepared by
nitration fluorobenzene or is there a good reason why this doesn't work?
On a slightly different issue; what is the purpose of trifluoromethyl groups on aromatic compounds? I have seen many reported syntheses where one or
more of the substrates ha this functional group in it but it doesn't seem to play any part in the reaction. Are the fluorine atoms on this functional
group reactive or inert? For instance is this functional group easily hydrolysable to a carboxylic acid group?
[Edited on 9-10-2017 by Boffis]
|
|
|
Crowfjord
Hazard to Others
Posts: 390
Registered: 20-1-2013
Location: Pacific Northwest
Member Is Offline
Mood: Ever so slowly crystallizing...
|
|
I believe trifluoromethyl groups are used where one wants a small, hydrophobic electronegative group. The fluorines are pretty inert, as I understand
it. Much less labile than the rest of the halogens. In medicinal chemistry, the trifluoromethyl is used when a group is needed that is more
hydrophobic than methyl, but about the same size.
|
|
|
Texium
Administrator
Posts: 4508
Registered: 11-1-2014
Location: Salt Lake City
Member Is Offline
Mood: PhD candidate!
|
|
Another property that is appealing in medicinal chemistry is that trifluoromethyl groups are not easily oxidized like methyl groups.
|
|
|
clearly_not_atara
International Hazard
Posts: 2691
Registered: 3-11-2013
Member Is Offline
Mood: Big
|
|
If you can make an N-heterocyclic carbene you can use this to prepare a phenol deoxyfluorinating reagent as follows:
NHC + Cl2 (maybe Br2?) >> NHC-Dichloride
NHC-dichloride + 2 F- >> NHC-difluoride + 2 Cl-
The rxns must be performed under anhydrous conditions. I think any fluoride salt wil work as long as it's soluble in the rxn medium. Then:
NHC-difluoride + phenol >> NHC-derived urea + fluoroarene + HF
http://www.organic-chemistry.org/abstracts/lit3/345.shtm
|
|
|
Boffis
International Hazard
Posts: 1836
Registered: 1-5-2011
Member Is Offline
Mood: No Mood
|
|
Thanks for the replies re the trifluoromethyl group guys.
I have found that there is a lot of information about the mononitration of fluorobenzene to give mainly the p-isomer which occurs more rapidly under
most conditions that the nitration of chloro or bromobenzene but I can't find anything on the dinitration.
|
|
|
Dr.Bob
International Hazard
Posts: 2656
Registered: 26-1-2011
Location: USA - NC
Member Is Offline
Mood: No Mood
|
|
A stated, the CF3- group is like a really large, but electron withdrawing alternate to a methyl group. It increases the lipohilicity of a compound,
generally increasing the half life in vivo, often reducing metabolism at and near the CF3, and it has about the steric bulk of a bromo group, with
less reactivity and molecular weight. In size R groups might be ranked as H < F < Me <=Cl < CF3 <= Br < I In an aromatic ring,
they are strongly electron withdrawing, maybe more than Cl or Br, don't have my handy Hammett value table here, but that can change the properties of
other groups on the ring, for instance removing charge from a carbonyl group (eg acyl group), or modifying the acidity of a benzoic acid. Since
methyl groups donate electrons, this is one of the best ways to test the effects of electronics, although a chlorine also works well for that swap. A
methyl and chloro group are very close in size, depending on which set of assumptions you use in modelling.
CF3 groups are inert towards most conditions, but can be hydrolyzed by strong base in some cases to a COOH group. This has been used as a way to
install a COOH group on some heterocycles, although I don't have a reference handy. But it takes pretty harsh conditions.
|
|
|
![[*]](images/xpblue/default_icon.gif){kind=icon}
