Author Topic: Novel Oxidative Demethylation of Eugenol  (Read 2587 times)

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Rhodium

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Novel Oxidative Demethylation of Eugenol
« on: August 04, 2003, 02:26:00 PM »
A Stabilized Formulation of IBX (SIBX) for Safe Oxidation Reactions Including a New Oxidative Demethylation of Phenolic Methyl Aryl Ethers
Aurélie Ozanne, Laurent Pouységu, Dominique Depernet, Bruno François, and Stéphane Quideau

Org. Lett. 5(16), 2903-2906 (2003)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/eugenol.demethylation.sibx.pdf)
DOI:

10.1021/ol0349965






Abstract

SIBX is a nonexplosive formulation of IBX that can be used as a suspension in a variety of standard organic solvents such as refluxing EtOAc and THF to oxidize safely alcohols into aldehydes and ketones. The use of hot THF is limited to the oxidation of allylic and benzylic alcohols. Most yields are comparable to those obtained with IBX or DMP. SIBX can also be used to perform oxygenative demethylation of 2-methoxyarenols into orthoquinones and catechols.

Full experimental + Prep of SIBX

(http://pubs.acs.org/subscribe/journals/orlef7/suppinfo/ol0349965/ol0349965si20030623_024608.pdf)

Various Preparations of SIBX using different solvents/oxidants/desensitizers

(https://www.thevespiary.org/rhodium/Rhodium/pdf/sibx.us2002107416.pdf)

4-Propenyl-benzene-1,2-diol [4-allylcatechol, 3,4-dihydroxyallylbenzene] (34).

To a stirred suspension of SIBX (857 mg, 1.5 mmol) in dry THF (14 mL, ca. 0.05 M) was added 4-allyl-2-methoxy-phenol [eugenol] (33) (0.7 mmol). After stirring in the dark at room temperature for 16 h, the white suspension was filtered out from the resulting red solution. The filter cake was washed with CH2Cl2 (20 mL) and the combined filtrate and washings were poured into water (30 mL). After separation, the aqueous layer was further extracted with CH2Cl2 (30 mL). The combined organic layers were washed with saturated aqueous NaHCO3 (4 x 15 mL) and treated with an aqueous solution (2 mL) of Na2S2O4 (730 mg, 4.2 mmol) for 10 min with vigorous stirring under nitrogen in the dark. The resulting yellow solution was washed with water (10 mL), brine (10 mL), dried over Na2SO4, filtered and evaporated to dryness to furnish 34 as a viscous orange solid (77%).


Phenols can also be oxidized by (S)IBX to o-quinones, which can be reduced to catechols by the same thiosulfate workup as above.
Ref: Org. Lett. 4(2), 285-288 (2002) DOI:

10.1021/ol017068j



IBX is very versatile, and another use is the oxidation of toluenes to benzaldehydes and alkylbenzenes to aralkylketones.
Ref: J. Am. Chem. Soc. 123, 3183-3185 (2001) DOI:

10.1021/ja004218x


Vitus_Verdegast

  • Guest
What an excellent find!!!
« Reply #1 on: August 05, 2003, 01:02:00 AM »
Rhodium!   :)  :)  :)

You're the best!  8)

77% yield from eugenol, using the cheap and readily available 2-iodobenzoic acid, isophtalic acid and oxone!

Marvelous!! Goodbye heavily watched sassy oil, welcome dirt-cheap, readily available and uncontrollable clove oil.


Rhodium

  • Guest
SIBX minus isophtalic acid for atom economy
« Reply #2 on: August 05, 2003, 11:54:00 AM »
I wonder if the isophtalic acid is even really needed, or if that is just one of those features they add to articles to make it look more interesting. I cannot imagine IBX blowing up without it being provoked.

Aurelius

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Rhodium
« Reply #3 on: August 05, 2003, 11:57:00 AM »
Sorry, but I've got to go for safety first.  I don't want to be the first to find out that IBX in THF is not a happy combination.  Is there a reason for isophthalic over phthalic?


Rhodium

  • Guest
IBX and precursors
« Reply #4 on: August 05, 2003, 12:24:00 PM »
Synthesis of IBX:

Post 219075 (missing)

(foxy2: "2-Iodoxybenzoic Acid (IBX) Synthesis", Chemistry Discourse)

Synthesis of IBX precursor:

Post 219077 (missing)

(foxy2: "2-Iodobenzoic Acid Synthesis", Chemistry Discourse)

psychokitty

  • Guest
GRRRRRR!!!
« Reply #5 on: April 19, 2004, 01:45:00 AM »
You are one clever bee, Rhodium.  I guess that is why you are the pricipal moderator here.

If it's of any interest to you, I found this article about a month ago using the typical keywords such as "eugenol" and "demethylation" and such.  However, I guess I was too slow in posting it. I was actually very interested in using the article as the flagship report of my recent collection of useful and intersting aryl ether-cleavage reactions.

And, well, so what.  I can see no reason why I still can't report my findings, regardless of your beating me to the punch.

And so I will.  Soon.

Good find, my friend.

PK

psychokitty

  • Guest
This could be a nice alternative to using SIBX
« Reply #6 on: October 05, 2004, 04:53:00 AM »
The follow article was authored by several reseachers, including the man himself, Alexander T. Shulgin.

In the future, it may prove to be adaptable to a better safer method for the oxidative demethylation of eugenol.

A Convenient Synthesis of Quinones from Hydroquinone Dimethyl Ethers. Oxidative Demethylation with Ceric Ammonium Nitrate
I'eyton Jacob, 111, Patrick S. Callery, Alexander T. Shulgin, and Neal Castagnoli, Jr.*
J. Org. Chem., Vol. 41, No. 22, 1976



Here are two excerpts from the article:

As a part of our studies on the metabolism and mechanism of action of psychotomimetic l-phenyl-2-aminopropanes, we required a mild method for the oxidative demethylation of p -dimethoxybenzene derivatives. We have found that ceric ammonium nitrate [Ce(NH4)2(NO& CAN] in aqueous acetonitrile will oxidize a variety of hydroquinone dimethyl ethers (a) to the corresponding quinones (b) often in high yield. The reaction can be carried out in the absence of strong acid, and is generally quite fast, requiring only a few minutes reaction time at room temperature. The selectivity and mildness of the reaction is illustrated by the fact that a variety of functional groups are tolerated.

General Procedure for Oxidative Demethylation.
Unless otherwise noted, the dimethoxy compound was dissolved in acetonitrile, and an aqueous solution of ceric ammonium nitrate (2-3 equiv CeIV) was added portionwise over 5 min. In most cases a transient blue-black color was observed. After stirring for 30 min at room temperature, the reaction mixture was extracted with chloroform. The chloroform extract was concentrated on a rotary evaporator and the crude product was purified by sublimation or recrystallization.

Here are two of the experimental examples printed in the article:

p-Benzoquinone (lb).
To a solution of p-dimethoxybenzene (la, 1.38 g, 10 mmol) in acetonitrile (25 ml) was added a solution of CAN (16.5 g, 30 mmol) in H20 (25 ml). The mixture was extracted with chloroform, the extract was concentrated under reduced pressure, and the residue was sublimed (160 "C, 20 mm) to give the yellow quinone lb (0.61 g, 5.7 mmol, 57%), mp 111.5-112.5 "C (lit.lo mp 114.5 "C).

2,5-Dimethyl-1,4-benzoquinone (2b).
The dimethyl ether 2all (1.0 g, 6.0 mmol) in acetonitrile was treated with aqueous CAN (8.8 g, 16 mmol) to yield the bright yellow quinone 2b which after sublimation (145 "C, 4 mm) gave 0.78 g (5.70 mmol, 95%) of pure product, mp 122.5-123.5 "C (lit.12 mp 123.5-125 "C).