2
$\begingroup$

This is a question from JEE Advanced 2019 (a highly valued engineering entrance exam in India), but the fact that we are ignoring basic rules of electrophilic substitution is disturbing. Correct me if I am wrong or missing something really important, but according to synergic electrophilic substitution, it should be an ortho attack from methoxy group as we know that an oxygen atom's conjugation would be more contributing than carbon's hyperconjugation and inductive effects combined. Overall, attack from 2-position (to alkyl group) instead of 3, as done in the question is what I mean to say.

But I also know that it (attack of 3-position) will make the compound to have a bridgehead, will it be stable then? And for overall compound, the stability of the compound, do we have to do a meta attack even in an activated ring?

SYNTHESIS OF TETRALONE

Improve this question
$\endgroup$
6
  • 2
    $\begingroup$ Could you crop your image to remove all irrelevant stuff and resize it for ease of readability? Also could you frame your question better, it took me sometime to make out what you were actually claiming. $\endgroup$
    – Sir Arthur7
    Jan 25 '20 at 16:43
  • $\begingroup$ Please rephrase your question. Are you suggesting that the cyclisation should go into a different position? $\endgroup$
    – Waylander
    Jan 25 '20 at 18:02
  • 1
    $\begingroup$ Yes ,cyclisation should go from 2 position and not 3 $\endgroup$
    – vanshita rawat
    Jan 25 '20 at 18:37
  • 1
    $\begingroup$ Is the editing helpful now? @waylander? $\endgroup$
    – vanshita rawat
    Jan 25 '20 at 18:43
  • 1
    $\begingroup$ If this ? is from an engineering exam, it is inefficient because the ketoacid is more readily available (FC of anisole and succinic anhydride) than the ketoaldehyde. My lab partner did the prep of 7-methoxytetralone. Works fine. $\endgroup$
    – user55119
    Jan 26 '20 at 16:56
3
$\begingroup$

I'm a little confused what OP's argument is. If you say "it should be a meta attack for methoxide group," then the question is showing an electrophilic substitution at meta-position to methoxy group. But, I understand you are wondering why substitution is at the meta-position to methoxy group rather than on ortho-position to methyl group. If that's what you meant, this is the answer to your curiosity:

The step in question is an example of Friedel-Crafts reaction. More precisely Friedel-Crafts acylation reaction. Here though, the substrate (aromatic nucleus) and the reagent (acyl chloride) are in the same molecule unlike any other typical inter-molecular reactions. In any inter-molecular Friedel-Crafts reaction involving 4-alkylanisole, substitution of acyl group mainly occurs on ortho-position to methoxy group, as you pointed out that "an oxygen atom's conjugation would be more contributing than carbon's hyperconjugation and inductive effects combined." I said here mainly because there would be some minor product from the substitution at ortho-position to alkyl group as well. For example, according to my experience, when Friedel-Crafts acylation reaction is performed in toluene and chlorobenzene, there were mixtures of products including o- and p-chloroacylbenzenes.

Now, we look at the problem in hand. This reaction come down to inter- versus intra-molecular acylation reactions. It's always intra-molecular reaction is much more faster than same type of inter-molecular reactions (here is acylation reaction of both kind) due to proximity. Thus, this phenomenon overcomes the deficiency of activation by methyl group versus methoxy group here, and gives most thermodynamically stable product, 7-methoxytetralone as the major product.

Edit: As OP's request, I include here an example for intra- vs inter-molecular acylation reaction (Ref.1):

Intra- vs Inter-Molecular Acylation Reactions

Reference:

  1. Yingju Xu, Mark McLaughlin, Cheng-yi Chen, Robert A. Reamer, Peter G. Dormer, Ian W. Davies, "A General Method for the Synthesis of 3,5-Diarylcyclopentenones via Friedel−Crafts Acylation of Vinyl Chlorides," J. Org. Chem. 2009, 74(14), 5100-5103 (https://doi.org/10.1021/jo900696k).
Improve this answer
$\endgroup$
6
  • $\begingroup$ So it's a minor but thermodynamically most stable product? $\endgroup$
    – vanshita rawat
    Jan 25 '20 at 18:47
  • $\begingroup$ Also can you provide a link for the fact stating the inter vs intra molecular acylation theory, it would be really helpful. $\endgroup$
    – vanshita rawat
    Jan 25 '20 at 18:49
  • $\begingroup$ The given product is the major product, if it is not the only product. My guess is it is the only product. $\endgroup$
    – Mathew Mahindaratne
    Jan 25 '20 at 18:54
  • 1
    $\begingroup$ You can easily goggle intra- vs inter-molecular reactions. $\endgroup$
    – Mathew Mahindaratne
    Jan 25 '20 at 18:55
  • 2
    $\begingroup$ It is worth remembering that the MeO group activates all positions on the ring, meta less than ortho but it is still activated. $\endgroup$
    – Waylander
    Jan 25 '20 at 19:05

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.