Author Topic: pyridine HCl/microwave demethylation for vanillin?  (Read 6799 times)

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indole_amine

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pyridine HCl/microwave demethylation for vanillin?
« on: October 12, 2004, 11:40:00 PM »
Hi!

I would like to know if anyone has ever had success with the microwave promoted pyridine*HCl demethylation depicted in

https://www.thevespiary.org/rhodium/Rhodium/pdf/ether.cleavage.py-hcl.mw.pdf

on vanillin? The only thing I was able to find about it was a side note, telling that someone once tried it without success (here:

Post 508710

(Cadenza: "microwave type etc.", Chemistry Discourse)
). He did use a modified mw oven, reflux setup and looong reaction times, though.

I just wondered because the paper seems to state that virtually every substituent on the phenyl is possible without interfering with the ether deprotection - but they use pulse irradiation (8 x 2 minutes at "medium low" in a standard domestic mw oven) and suggest using a stoppered vessel, rather than a reflux condenser.

Now without criticizing Cadenza, but maybe he just did run the reaction too long? Or maybe his problem was the everything else than inert atmosphere?

If you have any ideas about why the mentioned demethylation could NOT work with vanillin, I would be eager to hear them too (is vanillin somewhat hindered, compared to the substrates the authors of the article chose?)

TIA for answering my newbee questions!


indole_amine

indole_amine

  • Guest
demethylation with molten pyridine-HCl
« Reply #1 on: October 30, 2004, 07:19:00 AM »
Still noone with any experience in microwave vanillin demethylations? I can't believe it.
But this one looks cool, too:


Demethylation of 4-Methoxyphenylbutyric Acid Using Molten Pyridinium Hydrochloride on Multikilogram Scale
(Christopher R. Schmid, Christopher A. Beck, Jason S. Cronin, and Michael A. Staszak)
Org. Proc. Res. Dev., 8 (4), 670 -673, 2004
DOI:

10.1021/op0499526 S1083-6160(04)09952-9






Abstract:

4-Methoxyphenylbutyric acid (2) is smoothly demethylated in 3 h at 180 C when melted with pyridinium hydrochloride (Pyr·HCl), affording 4-hydroxyphenylbutyric acid (3), a key starting material for the preclinical candidate LY518674 (1). The adaptation of this chemistry to 22-L and pilot-plant scale is described, including findings to facilitate product isolation, selection of a compatible extraction solvent, and observation of an unusual relationship between the number of solvent extractions and the Pyr·HCl stoichiometry. To the best of our knowledge, this represents the first literature report of the use of this classic demethylation chemistry on multikilogram scale.


With special greets to LabTop... :)



indole_amine

indole_amine

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Q
« Reply #2 on: October 30, 2004, 07:33:00 AM »
In

https://www.thevespiary.org/rhodium/Rhodium/chemistry/methylenation.html#pyralcl

, a lewis acid (AlCl3) is used, together with pyridine, to affect the demethylation of vanillin. What is the reason behind using a lewis acid?

Thanks!


indole_amine

Captain_America

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Still noone with any experience in microwave...
« Reply #3 on: October 30, 2004, 02:41:00 PM »
Still noone with any experience in microwave vanillin demethylations?

Again why, oh why, when you can use HI that is so easily made in OTC fashion and it gives excellent yield of phenol, it also will give an ekvivalent of MeI which is a useful reagent. If you for some reason can't get make HI, you can do demethylation of vanillin using HCl, see; Tiemann; Haarmann;Chem.Ber.; 7; 1874; 620....

Maybe you can explain the advantages of the pyridine.HCl method over HI in the demethylation of vanillin?


indole_amine

  • Guest
?
« Reply #4 on: October 30, 2004, 05:21:00 PM »
I'm really sorry that I got interested in pyridine*HCl demethylations. It won't happen again, promised.
And in case you think I was maligning HI reductions; my apologies, wasn't my intention, won't happen again, promised.
(for your envy: I have access to labgrade 99.9% HI...)


indole_amine

ApprenticeCook

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(for your envy: I have access to labgrade...
« Reply #5 on: October 31, 2004, 04:57:00 AM »
(for your envy: I have access to labgrade 99.9% HI...)
Gas bottle of HI, and? as for making it, thats easier than trying to buy and explain or steal the bottle from your workplace...

-AC


Offline Etxeko

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Re: Q
« Reply #6 on: May 15, 2015, 05:22:53 PM »
a lewis acid (AlCl3) is used, together with pyridine, to affect the demethylation of vanillin. What is the reason behind using a lewis acid?

Thanks!


An anhydrous Lewis acid is used because the aluminium cation reacts with the lone pair of oxygen of the methyl ether, and pyridine is used to neutralize the protic acid formed in the reaction.

« Last Edit: May 15, 2015, 05:30:03 PM by Etxeko »