Sciencemadness Discussion Board

p-fluoro benzaldehyde

chemrox - 5-2-2007 at 12:48

p-fluoro benzaldehyde is expensive stuff. Is there a way to do this that doesn't require Fl2?

Sauron - 5-2-2007 at 12:55

Buy or make p-aminobenzaldehyde then do a diazo reaction, you can put a F on that position that way.

F2? You really don't want to work with F2.

garage chemist - 5-2-2007 at 13:53

F2 is useless in organic chemistry. It can not be used to make defined fluorinated organics. Read up what happens if F2 is contacted with organics (super violent reaction, with total destruction of the carbon skeleton and CF4 and HF as the main products).

Para- fluorobenzaldehyde would be prepared from para- aminotoluene (not para-aminobenzaldehyde, the aldehyde group likely wont survive the Balz- Schiemann reaction), made from the easily prepared para- nitrotoluene.
The classic Sandmeyer reaction on the diazotised amine does not work for fluorine.
It is necessary to precipitate the diazonium ion with fluoroboric acid as the diazonium tetrafluoroborate and heat this salt dry until decomposition (Balz- Schiemann reaction, see the Orgsyn preparation for fluorobenzene). The products are the fluoroaromatic (in this case para- fluorotoluene) and boron trifluoride (a valuable byproduct which should be captured, this can be used for other things).
Then oxidise to the aldehyde in which manner you regard as the most convenient (e.g. by halogenation followed by hydrolysis).

Para- fluorobenzaldehyde would be a very cheap substance if either there was a demand for large amounts of it or the production process, which uses very cheap materials, is upscaled by oneself.

Sauron - 5-2-2007 at 21:04

Good point, @GC

chemrox - 5-2-2007 at 23:26

Quote:
[see the Orgsyn preparation for fluorobenzene).


Indeed! Thanks for the pointers. I wasn't thinking about this very clearly .. you got me going.

SecretSquirrel - 6-2-2007 at 01:36

This is an old Hive post.

Preparation of 4-fluorobenzaldehyde from 4-chlorobenzaldehyde

140 g (1 mol) of 4-chlorobenzaldehyde, 58 g (1 mol) of potassium fluoride, 5 g of nitrobenzene and 7.98 g of tetrakis(diethylamino)phosphonium bromide (phase transfer catalyst) are placed in a 500 ml four-neck flask fitted with thermometer, anchor stirrer and reflux condenser with bubble counter. The mixture is subsequently heated while stirring to 190.degree. C. and allowed to react for 20 hours. After the reaction is complete, the reaction mixture is allowed to cool, dissolved in chlorobenzene, insoluble constituents are filtered off and the product (4-fluorobenzaldehyde) is purified by fractional distillation under reduced pressure.

Yield: 77%

Selectivity: 93%

Benzaldehyde content: 0.01%

Reference: Patent US6166242 - Method for producing compounds containing fluorine, in particular fluorobenzaldhydes and fluorobenzonitriles

[Edited on 6-2-2007 by SecretSquirrel]

chemrox - 8-2-2007 at 22:29

Great information in all the above; thanks. Would propylene or ethylene glycol work for the PTC?

not_important - 8-2-2007 at 22:35

Quote:
Originally posted by chemrox
Great information in all the above; thanks. Would propylene or ethylene glycol work for the PTC?


In this case not likely. Simple glycols aren't really PTC in the first place, just useful solvents. And I'd bet that the PTC used here is shuttling the floride ion into the organic layer, the PTC being a halide salt while a glycol has little interaction with halide ions.

Sandmeyer - 14-2-2007 at 14:48

Don't have the SciFi around, but I meen what's wrong with Vilsmeyer (or variation) on fluorobenzene? Clearly, I see no point in not having the F on the Ar nucleus from the beggining...

[Edited on 14-2-2007 by Sandmeyer]

not_important - 14-2-2007 at 16:10

Vilsmeyer takes an activated arene, and the fluorine will be midly deactivating, so I'm not sure the reaction would go - at least with any decent yields.

Sandmeyer - 15-2-2007 at 04:47

F is mesomericly activating, but you are right Vilsmeyer is IMO only useful for indole and other highly electron-rich heterocycles and polymethoxybenzenes. Otherwise there is other high-yielding formylation method, but it involves the use of Cl2CH-O-Me/TiCl4. There is the possibility to do chloromethylation, followed by a Sommelet, works good on less activated substrates (towards E+), see Vogel.

[Edited on 15-2-2007 by Sandmeyer]

not_important - 15-2-2007 at 10:14

Yeah, chloromethylation would go. Fluorinr may be mesomericly activating, but it is also electron withdrawing which is deactivating for many reaction.

Or go p-nitro-toluene => p-toluidine => p-fluoro-toluene and oxidise that to the aldehyde.

Nicodem - 15-2-2007 at 11:27

Industrially, the flourobenzene can be formylated by the Gattermann-Koch Reaction (US6455739). It can be also formylated by the in situ formed HCOF from methyl formate and HF/BF3 (US5068450). Both are completely useless for laboratory scale preparation.

Sandmeyer - 15-2-2007 at 12:17

Quote:
Originally posted by not_important
Yeah, chloromethylation would go. Fluorinr may be mesomericly activating, but it is also electron withdrawing which is deactivating for many reaction.


F's inductively deactivating effect is of no significance for a site as far away as pos 4 of an arene, that also explains why aromatic electrophilic substitution is so regioselective for pos 4 on F-Ar's...
Quote:

Or go p-nitro-toluene => p-toluidine => p-fluoro-toluene and oxidise that to the aldehyde.


yeah, right, everyday...

Sergei_Eisenstein - 15-2-2007 at 12:24

In case I needed a sizeable amount of p-fluorobenzaldehyde, I'd look into the preparation of the organomagnesium compound derived from p-bromofluorobenzene, and reacting this with DMF. I once read a reference - which I cannot retrieve thanks to the junk - where the organolithium from p-bromofluorobenzene was maded (with BuLi) at non-cryogenic temperatures, and subsequently reacted with carbon dioxide. It might be a fair challenge.

chemrox - 23-2-2007 at 23:38

Quote:
In this case not likely. Simple glycols aren't really PTC in the first place, just useful solvents. And I'd bet that the PTC used here is shuttling the floride ion into the organic layer, the PTC being a halide salt while a glycol has little interaction with halide ions.


http://www.sigmaaldrich.com/Brands/Fluka___Riedel_Home/Organ...

not_important - 24-2-2007 at 00:15

Quote:
Originally posted by chemrox
Quote:
In this case not likely. Simple glycols aren't really PTC in the first place, just useful solvents. And I'd bet that the PTC used here is shuttling the floride ion into the organic layer, the PTC being a halide salt while a glycol has little interaction with halide ions.


http://www.sigmaaldrich.com/Brands/Fluka___Riedel_Home/Organ...


Ah, but you wrote
Quote:
Originally posted by chemrox
Great information in all the above; thanks. Would propylene or ethylene glycol work for the PTC?


asking about those simple glycols, while the link talks about polyethylene glycols. PEGs do work as PTC, a bit similar to crown ethers. The long chain of repeat -CH2CH2-O- groups 'wrap around' cations such as Na+ or K+ and solvate them into the organic layer.

Note that the smallest PEG listed in your reference is PEG 200, having an average MW of 200. As the 'monomer' has a MW of 44.05, the average PEG molecule having more than 4 repeating units of [CH2CH2O] in it, the other listed will be 8, 12, and 20 units in average length.


"glycols for PTC" can be downlaoded here
http://www.glymes.com/download.php

Geneal PTC info
http://www.iupac.org/publications/pac/1986/pdf/5806x0857.pdf

chemrox - 25-2-2007 at 23:43

So, please clear this up for me, are you saying PEG 400 would work as a PTC but "polyethylene glycol" of presumably much shorter length, not? If so that would be consistent with the reference and what you said earlier.

not_important - 26-2-2007 at 00:54

No, I'm saying that for many reactions and conditions you need more than 2 oxygens, from stuff I've read 5 or 6 oxygens (around PEG 200) is where the effectivrness seems to kick in. There are some cases in which even ethylene glycol itself will catalyse a reaction, but in most of those cases there are much more effective catalysts, and it's not clear if what is being seen is simple a solvent effect.

You can't get much shorter than PEG-200 and still be 'polyethylene glycol" Diethylene glycol would be PEG-100, triethylene glycol PEG-150, in a handwaving sort of way.

The mono, di, and tri glycols are useful high boiling protic solvents, in some cases running reactions in them at their boiling point can greatly speed up a reaction, and even change the product mix.

grignard

Tsjerk - 26-2-2007 at 10:32

I was thinking about this a while ago, I have a little bottle of 1-fluor-4-bromobenzene somewhere. If you would make the grignard out of this, it shouldn't be to difficult to make the benzaldehyde.

Product of trade

meme - 25-8-2008 at 10:06

p-fluorobenzaldehyde is available from many sources as a fine chemical. I'm not sure if you can order it, or if it would be cost efficient, or any number of things, but I bet an asian firm would be able to supply this very cheaply.

Klute - 25-8-2008 at 10:54

Panreac offers it at under 50E for 50mL.... It is a colorless liquid, with a very pleasant , delicate almond smell simialr to benzaldehyde but less intense.

DNA - 25-8-2008 at 22:40

Bear in mind that tetrakis is EXPENSIVE and needs to be stored in the freezer just to mention.