Author Topic: P2P from Aniline! (Meerwein arylation)  (Read 9027 times)

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Antoncho

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Meerwein works on electron-rich anilines?
« Reply #20 on: January 08, 2004, 04:00:00 AM »

Patent US4604243

Abstract: An olefin, especially an activated olefin, is arylated by reaction with an arylamine, such as an aniline, in an inert polar organic solvent and in the presence of an alkyl nitrite, a hydrogen halide, and a catalytic amount of a copper catalyst having the copper in an oxidation state below +2.





Alas, if you look into the examples, you'll find out that only for the electron-poor nuclei did they get decent yields :(  In case of 3,4-diMeO- the yield was in ~30% range.

If a patent says that something is a 'suitable' substrate, it usually means nothing to bee sure of.



Antoncho


Antoncho

  • Guest
An excellent post!
« Reply #21 on: January 13, 2004, 05:49:00 AM »
A very good article, Lego! Thank you!

Don't you find it strange that there's no mention of electrophyllicity of the aryl diazonium counterpart as the important parameter?

Another thing i'd like to notice (and, more specifically, ask Xicori if he ever smelled this :) ):

As noted by the underlining above, chloroacetone,... are by-products always encountered in Meerwein arylations.

Does this side-rxn happen to a great extent?


Also, form this article can bee unquestionably inferred that acetone should bee the prefered solvent:

Since ArH is probably formed by the reaction of Ar• with a readily abstracted hydrogen atom, solvents like ethers and alcohols with the grouping H-C-O are unsuitable for Meerwein arylation. Despite the ease of hydrogen abstraction from acetone, most workers persist in using it because of availability, convenience, cost, and tradition.

Lego

  • Guest
Some more comments on the Meerwein arylation
« Reply #22 on: January 15, 2004, 01:37:00 AM »
@Antoncho:
Thanks for the support!
Chloroacetone is only formed under classical Meerwein conditions, i.e. with acetone/H2O as solvent, therefore it is very unlikely that chloroacetone was a byproduct in Xicori's reaction.

Don't you find it strange that there's no mention of electrophyllicity of the aryl diazonium counterpart as the important parameter?
Yes, but unfortunately the article is too old to send the author an email and ask him  ;)


@Nicodem:
You are absolutely right (concerning the side-reaction of acetone) in theory, as the author is right to state that alcohols are not suitable solvents, but in practice both solvents seem to work.


@Xicori:
Repeating this reaction is an excellent idea. But Lego would like to suggest one or two things:
For your second run change nothing than the solvent (acetone instead of methanol). In the first reaction twice the amount (compared to the patent) of CuCl was used and the pH was not adjusted. The review claims that low concentrations of copper reduce side-reactions (Sandmeyer, etc.) but if two reaction parameters are changed it is not possible to say what reaction parameter influenced the yield. The next time the reaction is performed  ;)  one could either buffer the solution or use CuCl2 and so on, as long as the Hive's community has found the ideal reaction parameters.
Your old CuCl was much better for the reaction than new one  ;) .





Chloroacetone is formed as a by-product if acetone is used as solvent but as a mixture with water. Chloroacetone is miscible with water and its boiling point is 119°C, so nobee has to bee afraid of evaporating chloroacetone but one should bee carefull nonetheless.

Phase transfer catalysis: Hm, Lego's idea was not that new, the author suggested it 30 years ago  :( . But there is one thing to mention: in this reaction there is water soluble cation (phenyldiazonium) which should react with a non-polar molecule (isopropenyl acetate). If one of the standard PTCs (any quaternary ammonium compound like a tetrabutylammonium salt or benzenetriooctyl ammonium chloride) not the phenyldiazonium cation but the counter anion (chloride) is soluble in the organic phase. Therefore an anionic phase transfer catalyst has to bee used. Sodium dodecylbenzenesulfonate is used as PTC for preparation of azo dyes in the reaction of phenyldiazonium tetrafluoroborates. As this PTC is well established in diazonium chemistry it might bee a good point to start from. Another interesting PTC are poly(ethylenglycol)s, especially PEG 400, which is non-ionic.




The Meerwein arylation might bee interesting not only for plain P2P but also for substituted ones. One could start from 2,5-dibromoaniline (25 g ~ 100$) to get 2,5-dibromo-P2P or 2,5-dibromo-phenylacetaldehyde, then methoxylate and reduce to get 2,5-DMA or 2C-H. Another possiblity is to use 4-chloroaniline (100 g ~ 10$) to get 4-chloro-P2P which is reacted sodium methanethiolate to get 4-methylthio-P2P which is an excellent precursor for the interesting compound MTA. You want mescaline or TMA? Meerwein arylation with 4-methoxyaniline aka p-anisidine (250 g ~ 45$), dibrominate and get 3,5-dibromo-4-methoxy-P2P, then a methoxylation and a reductive amination to get your desired compound.


Rhodium

  • Guest
P2P's are pH sensitive
« Reply #23 on: January 15, 2004, 03:36:00 AM »
You cannot methoxylate halo-substituted P2P's, as the basic conditions would be too harsh on the ketone function. It would have to be protected:

Post 482354

(Rhodium: "Ketone ketal protection", Newbee Forum)



Xicori

  • Guest
Acetone = not good
« Reply #24 on: February 06, 2004, 04:59:00 PM »
High Bees!

The reaction was tried out once more, but this time acetone instead of methanole was used.

During the addition of the diazonium salt the solution turned a deep black, and also a very bad smell was noticed. The intense black colour made it nearly impossible to seperate the layers using DCM, bacause both layers had the same colour.

A lot of (acidic) gasses envolved during the reaction, so a gas trap filled with NaOH-Solution was used to protect the chemist    ::)

After workup a lot of unreacted isopropenyl acetate & a lot of black tar was recovered  :(

This seems to make methanole the one and only choice for this reaction, because with methanole the reaction ran very clear.

The distilled product from the reaction must(!) be further purified via the bisulfite adduct, because there seems to be a lot of phenole contaminating the final product (phenole´s boiling point is close to the boiling point of p2p).

best wishes,
xicori