@Antoncho:
Thanks for the support!
Chloroacetone is only formed under
classical Meerwein conditions, i.e. with acetone/H
2O 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 CuCl
2 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.
