Sciencemadness Discussion Board

Alkylation with chloracetic acid

Mildronate - 1-12-2010 at 13:15

Is it posible benzene alkylation with monochloracetic acid by Fridel Craft to prepare phenylacetic acd

[Edited on 1-12-2010 by Mildronate]

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Rich_Insane - 1-12-2010 at 14:43

I think chloroacetone and AlCl3 will work better to yield phenylacetone. From there, I believe you can oxidize to phenylacetic acid. I don't think you can attach the carboxyl group to the ring.

madscientist - 1-12-2010 at 15:51

Sounds messy. Carboxylic acids can acylate aromatic rings as well. I'm betting on tar.

Nicodem - 1-12-2010 at 16:19

It is not possible. Under Friedel-Crafts reaction conditions, with a large excess of AlCl3 you could utmost obtain phenacyl chloride, but even this is doubtful as FC acylations with free carboxylic acids tend to be very inefficient (except for some exceptions using catalysts other than AlCl3).
Quote: Originally posted by Rich_Insane  
From there, I believe you can oxidize to phenylacetic acid. I don't think you can attach the carboxyl group to the ring.

What kind of an oxidation method would give phenylacetic acid from phenylacetone? As far as I know, not even the haloform reaction would, just check the pKa different between the methyl and methylene groups.

DDTea - 1-12-2010 at 19:39

If you look at the mechanism by which Friedel-Crafts alkylation proceeds, a carbocation is formed:

R-Cl + AlCl3 --> R(+) + AlCl4(-)

If R-Cl is chloroacetic acid, you're going to be forming a primary carbocation adjacent to an electron withdrawing group (carboxyl). Not a very good carbocation! Based on that, we can conclude this reaction would be highly unlikely.

smuv - 2-12-2010 at 21:05

No it will go. Just not as you want. The product mixture will be very complex. The major theme though is that phenacylchloride will be produced, which may either react at the carbonyl (2x) and at the halide. If you want more info about this kind of thing, a decent scientific library should have a couple good reviews of the friedel-crafts reaction, most include info about using oxygen containing electrophiles (due to industrial interest). In short this reaction has been studied, though I am not going to dig it up, because there is no way it will provide what you want.

[Edited on 12-3-2010 by smuv]

DDTea - 2-12-2010 at 21:11

Quote: Originally posted by smuv  
No it will go. Just not as you want. The product mixture will be very complex. The major theme though is that phenacylchloride will be produced, which may either react at the carbonyl (2x) and at the halide. If you want more info about this kind of thing, a decent scientific library should have a couple good reviews of the friedel-crafts reaction, most include info about using oxygen containing electrophiles (due to industrial interest). In short this reaction has been studied, though I am not going to dig it up, because there is no way it will provide what you want.

[Edited on 12-3-2010 by smuv]


Come on smuv, don't blue ball us!

I'm actually really interested in reading about that, even if the product is entirely different from the intended one at the beginning of this thread.

smuv - 2-12-2010 at 21:38

lol.

it is for sure mentioned in one or both of these books (they are both good to flip through though):

Friedel-Crafts chemistry,
by Olah, George A. 1927- Published 1973

Anhydrous aluminum chloride in organic chemistry,
by Thomas, Charles Allen, 1900- Published 1941

By my understanding of these reactions, the reaction should proceed, stepwise to 2,2,2-triphenyl(chloroethane). And then, go on to react at the halide. The reaction would probably be done in refluxing benzene. DON'T think you can get say phenacyl chloride out of this or one of the steps along the way. These reactions are very hard to control because the conditions are heterogeneous (although performing the reaction in nitrobenzene or a nitroparafin can get around this).

You might have a shot getting phenylacetic acid from a friedel crafts of, BF3 (or any BX3) with fluoroacetic acid and benzene. But I think oxygen is too small to allow that trick to work. Without a lit search, I can only think of indirect methods to get phenylacetic acid by firedel-crafts. For example 2,2,2-trichloro(fluoroethane) with BF3 in benzene followed by hydrolysis of 2,2,2-(trichloroethyl)benzene to phenylacetic acid. It is possible that TiCl4 or SnCl4 coordinate with halides in preference to oxygen (allowing the FC to produce phenylacetic acid from chloroacetic acid), but I would have to lit search to find that (if you are so inclined look up the mechanism for formylations with dichloromethyl methyl ether).

p.s. this post is relying a lot on my memory over referred publications...grain of salt...

[Edited on 12-3-2010 by smuv]

[Edited on 12-3-2010 by smuv]

Rich_Insane - 10-12-2010 at 15:36

Sorry,

I meant one could prepare the aldehyde and oxidize to the carboxylic acid. I doubt one could prepare PAA efficiently using FC.

There's probably some theoretical pathways out there though.

ScienceSquirrel - 11-12-2010 at 11:55

Easy ways to make an arylacetic acid is to start from the arene or the methyl arene.
The arene can be reacted with formaldehyde and a halogen acid to form the halomethyl arene, alternatively the methyl arene can be side chain halogenated. This can converted to the Grignard or the lithium compound and then reacted with carbon dioxide to form the arylacetic acid.
Alternatively it can reacted with cyanide and then hydrolysed to form the acid.
The importance of arylacetic and more particularly 2 aryl propionic acids as drugs, plus the use of phenylacetic acid as a synthon has resulted in an enormous effort at their synthesis.

Anyone who could do;

isobutylbenzene + 2-chloropropionic acid ----> Ibuprofen

would be flavour of the month at a lot of chemical companies and would get a big wodge!

Mildronate - 19-6-2011 at 01:14

But maybe I can make ester or salt of chloracetic acid and then alkylation?

Nicodem - 19-6-2011 at 01:41

Quote: Originally posted by Mildronate  
But maybe I can make ester or salt of chloracetic acid and then alkylation?

Its been half a year and you still did not bother reading a single review article on Fridel-Crafts alkylations and acylations?

Alkyl carboxylates react just like carboxylic acids, except in that you also get the corresponding alkylbenzenes as side products to the aryl ketones.

Salts of carboxylic acids are bases. You need acid catalysis for the Fridel-Crafts reactions. Acids are quenched by bases, and vice versa.

azo - 19-6-2011 at 04:14

If the desired product is phenylacetic acid why would you go to all that trouble when everyone knows the hydrolisis of benzyl cyanide is the best way.
Or just as simple is to use the esters of phenylacetic acid


Then again theres nothing like taking 3 steps foward and 5 steps backwood is there.:D


regards azo

Mildronate - 19-6-2011 at 07:20

Maybe its not the best ;)