I'm trying to figure out how to get the following reaction: (coumarin from eugenol)

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My immediate thoughts are

  1. $\ce{OH}$ and $\ce{OCH3}$are bad leaving groups.
  2. Could I just add $\ce{HI}$ to the $\ce{C10H12O2}$ to convert the methoxy ($\ce{OCH3}$) group to an $\ce{OH}$group? Then, I could add $\ce{Zn}$ to remove the $\ce{OH}$groups?
  3. Or, is there a way to make the methoxy ($\ce{OCH3}$) group into methanol, which would be a better leaving group?
  4. Once the methoxy and hydroxy groups are removed, I'm left with the benzene ring and the attached butene. I would need to add the $\ce{CO2}$ to form the second benzene ring, but I'm not sure how this would be done.
  5. I might be thinking about this all the wrong way. I was thinking that I need to remove the methoxy and hydroxy groups since they're on a benzene ring, and my product's benzene ring doesn't have these groups. Maybe I don't need to get rid of the methoxy and hydroxy groups at all. Maybe I just need to shift the bonds around?
  • 2
    $\begingroup$ Look up the Claisen rearrangement. Boron tribromide is the standard reagent for removing Me from phenol $\endgroup$
    – Waylander
    Apr 22 '17 at 15:35
  • $\begingroup$ Could you give any contex? The product is a very common, cheap chemical with no obvious route from the starting material - is this homework question? Sadly, textbook problems are aften very far from real syntheses. $\endgroup$ Jan 18 '18 at 23:44

Since no-one has offered an answer I'm going to try but as I have no database access some of this is a bit flaky.

  1. Heat (maybe microwave) to give multiple Claisen rearrangement products then separate to isolate 2-allyl, 6-methoxyphenol. This is the flakiest step.

  2. Hydroborate with oxidative work-up to take the allyl to propionic acid.

  3. Ring close (PTSA, Toluene)

  4. Reflux over activated MnO2 to introduce double bond.

  5. Treat with BBr3 to remove Me from MeO group

  6. Zn reduction of OH to H


I am in agreement with the comments of @jerepierre and @Jan Rzymkowski. The deoxygenation of phenols by zinc dust is used on occasion on SE but I have been unable to find it in the primary literature. Jan is correct. Who would try to convert eugenol (1) to coumarin (10) when salicylaldehyde is the logical precursor? Nonetheless, I'll offer a solution that is somewhat similar to the one provided by @Waylander.

The base t-BuOK in DMSO isomerizes eugenol (1) to isoeugenol. Protection of the phenolic group of isoeugenol as the acetate permits conversion of the carbon chain to a carboxyl group via vanillic acid (3). The decarboxylation of vanillic acid is modeled after a literature report for the conversion of benzoic acid 11 to propofol (12). [Cucumber juice is claimed to effect this reaction via a biotransformation.] Phenol 4 is allylated and subjected to Claisen rearrangement to afford allylphenol 6. The allyl chain can be parlayed into an aldehyde group by the methods employed earlier. Salicylaldehyde itself has been converted into coumarin using the Perkin condensation. Waylander's use of boron tribromide for demethylation is an excellent choice. If indeed zinc dust works, reduction of the double bond may be problematic. Reinstallation of the double bond lacks elegance but it can be accomplished [a) LDA/THF, PhSSPh; b) H2O2; c) heat.]

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