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When does an aromatic ether break its bonds?
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Jo Foster
When does an aromatic ether break its bonds?
Demethylation of phenolic ethers generally requires some pretty extreme conditions. In verifying the structure of vanillin Tiemann and Haarmann (page 620) demethylated it successfully with dilute hydrochloric acid at up to 200°C. To illustrate the "usual" extreme conditions for demethylation, the authors first tried fuming hydroiodic acid at up to 130°C, but that gave an "amorphous, iodine-containing, black" decomposition product.
More recent work by Bomon et al. successfully used catalytic dilute HCl in an autoclave at up to 250°C to demethylate various phenolic ethers. The authors also give a very good review of demethylation reagents/techniques for comparison.
Tiemann and Haarmann, Ber., 7, 608 (1874)
Bomon et al., Green Chem., 23, 1995 (2021)
Funny how little has changed in those almost 150 years!
Demethylation of phenolic ethers generally requires some pretty extreme conditions. In verifying the structure of vanillin Tiemann and Haarmann (page 620) demethylated it successfully with dilute hydrochloric acid at up to 200°C. To illustrate the "usual" extreme conditions for demethylation, the authors first tried fuming hydroiodic acid at up to 130°C, but that gave an "amorphous, iodine-containing, black" decomposition product.
More recent work by Bomon et al. successfully used catalytic dilute HCl in an autoclave at up to 250°C to demethylate various phenolic ethers. The authors also give a very good review of demethylation reagents/techniques for comparison.
Tiemann and Haarmann, Ber., 7, 608 (1874)
Bomon et al., Green Chem., 23, 1995 (2021)
Funny how little has changed in those almost 150 years!
The Zeisel reaction as described here reads like submitting the substrate to refluxing $\ce{HI}$ with $\ce{HOAc}$. This seems much more aggressive than the oxymercuration conditions in the first scheme, where you need a bit of $\ce{H+}$ to transfer the intermediate enol into the more stable ketone by keto-enol tautomerism. Compare e.g., with an entry on Organic Synthesis:
The Zeisel reaction as described here reads like submitting the substrate to refluxing $\ce{HI}$ with $\ce{HOAc}$. This seems much more aggressive than the oxymercuration conditions in the first scheme, where you need a bit of $\ce{H+}$ to transfer the intermediate enol into the more stable ketone by keto-enol tautomerism. Compare e.g., with an entry on Organic Synthesis:
The story I heard, perhaps apocryphal, was that the hydration reaction was discovered by the accidental breakage of a mercury thermometer while stirring a vessel containing an alkyne and aqueous sulfuric acid lending credence to the catalytic nature of the reaction. BTW: A gold catalyst shows 100% regioselectivity for this substrate in favor of the anisole end. [DOI:10.1039/d1cc01837j ]More
Hydration of the triple bond is opposite that of the original example, which is the likely site of hydration. Mercuric ion hydration of triple bonds is catalytic, not stoichiometric. NaBH4 is not needed. Hydration of double bonds is stoichiometric and requires NaBH4 reduction. NaBH4 here would reduce any ketone present.More
, are $\ce{C#C}$ triple bonds so much more susceptible to oxymercuration than $\ce{C=C}$ double bonds? I agree for the point of reduction of the ketone by $\ce{NaBH4}$.More
Demethylation of phenolic ethers generally requires some pretty extreme conditions. In verifying the structure of vanillin Tiemann and Haarmann (page 620) demethylated it successfully with dilute hydrochloric acid at up to 200°C. To illustrate the "usual" extreme conditions for demethylation, the authors first tried fuming hydroiodic acid at up to 130°C, but that gave an "amorphous, iodine-containing, black" decomposition product.
More recent work by Bomon et al. successfully used catalytic dilute HCl in an autoclave at up to 250°C to demethylate various phenolic ethers. The authors also give a very good review of demethylation reagents/techniques for comparison.
Funny how little has changed in those almost 150 years!
Demethylation of phenolic ethers generally requires some pretty extreme conditions. In verifying the structure of vanillin Tiemann and Haarmann (page 620) demethylated it successfully with dilute hydrochloric acid at up to 200°C. To illustrate the "usual" extreme conditions for demethylation, the authors first tried fuming hydroiodic acid at up to 130°C, but that gave an "amorphous, iodine-containing, black" decomposition product.
More recent work by Bomon et al. successfully used catalytic dilute HCl in an autoclave at up to 250°C to demethylate various phenolic ethers. The authors also give a very good review of demethylation reagents/techniques for comparison.
Funny how little has changed in those almost 150 years!
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The Zeisel reaction as described here reads like submitting the substrate to refluxing $\ce{HI}$ with $\ce{HOAc}$. This seems much more aggressive than the oxymercuration conditions in the first scheme, where you need a bit of $\ce{H+}$ to transfer the intermediate enol into the more stable ketone by keto-enol tautomerism. Compare e.g., with an entry on Organic Synthesis:
(credit to Org. Synth. 1973, 53, 94)
which, in the case of acetylenic bonds looks like this:
(credit to Wikipedia)
Thus, in your case:
My anticipation (though speculation) is, the reaction conditions to cleave off the methyl ether easily knock-down the enolizable ketone.
The Zeisel reaction as described here reads like submitting the substrate to refluxing $\ce{HI}$ with $\ce{HOAc}$. This seems much more aggressive than the oxymercuration conditions in the first scheme, where you need a bit of $\ce{H+}$ to transfer the intermediate enol into the more stable ketone by keto-enol tautomerism. Compare e.g., with an entry on Organic Synthesis:
(credit to Org. Synth. 1973, 53, 94)
which, in the case of acetylenic bonds looks like this:
(credit to Wikipedia)
Thus, in your case:
My anticipation (though speculation) is, the reaction conditions to cleave off the methyl ether easily knock-down the enolizable ketone.
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