Is it feasible to manufacture p-nitroacetophenone by reacting di(p-nitrophenyl)cuprate and acetyl chloride?

I think it should be possible but is there any chance that the NO2 being a highly deactivating group does not allow the substitution?

  • $\begingroup$ I'd rather worry about using acyl instead or alkyl. $\endgroup$ – Mithoron Jul 12 '18 at 18:57
  • $\begingroup$ @Mithoron Why ? My book says its not possible as one would have to make organocopper compound from onganolithium reagent here but the no2 group does not allow it. I could not understand it. Can you explain? $\endgroup$ – tatan Jul 12 '18 at 18:59
  • $\begingroup$ Well, that may be a problem, but in a different way then you mentioned in question. $\endgroup$ – Mithoron Jul 12 '18 at 19:03
  • $\begingroup$ @Mithoron But isn't it already an organocopper compound? I don't see why it should organolithium! $\endgroup$ – tatan Jul 12 '18 at 19:05
  • $\begingroup$ first chemistry.stackexchange.com/questions/32079/… second metal exchange with Cu and finally reaction with AcCl but this doesn't make much sense in practice even if would work. One should just nitrate acetophenone, or maybe even buy nitrated. $\endgroup$ – Mithoron Jul 12 '18 at 19:19

In general, reactions involving organocuprate reagents ( Gilman reagents ) are used in nucleophilic aliphatic substitution ( example: chloromethane reacting with organocuprate containing methyl groups to obtain ethane ). In this case, you are dealing with a reaction that, if it worked, would have an addition-elimination mechanism. However, we can approach the synthesis in a different way. We can start from p-chloronitrobenzene. You know that this aromatic substrate is not electron rich ( because it has the nitro group which is extremely electron withdrawing ). In comparison to benzene, p-chloronotrobenzene is more “deactivated” when it comes to electrophilic aromatic substitution. At this point, I believe you know where this is going. Rather than making the aromatic ring a nucleophile like you proposed, we make use of its low reactivity in electrophilic substitution and its high reactivity in NUCLEOPHILIC AROMATIC SUBSTITUTION. Thus, we can use a nucleophile to displace the chlorine atom with another group ( a substitution which proceeds through a Meisenheimer ion ). What kind of nucleophile should we use to obtain an acetyl group in para position ? It would be idyllic if we could just substitute the chlorine atom with an acetyl anion, but that is impossible. We could use use instead reagents that “mask” this theoretical ion ( sinthon ). For more information regarding sinthons, read about retrosynthesis. So, in one method, we will react p-chloronitrobenzene with acetylide ion, yielding p-nitrophenylacetylene. Hydrating this alkyne in the presence of mercury ( II ) salt and sulfuric acid will result in the obtention of your desired compound. In another method, we take p-chlorobenzene and react it with the anion of nitroethane and then, using Nef reaction, we convert the nitro group to a ketone. In conclusion, your method is not really feasible due to the nature of organocuprate reagents. I have proposed alternative methods that I think they would work better ( note that they are lab methods ). It is recommended to find lab methods that do not imply oxidation reactions in order to ensure high yields. Let me know if you do not agree.

  • 2
    $\begingroup$ A lot of labs will not permit the use of mercury these days. $\endgroup$ – Waylander Jul 13 '18 at 14:26
  • 3
    $\begingroup$ Well could you break your block of text into paragraphs? It is very hard to read. $\endgroup$ – Nilay Ghosh Jul 13 '18 at 14:55

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