Another hopeful eugenol-safrole thread

[El_Zorro]

Alright, how 'bout this one.  When you put a strong base in solution with eugenol, the -OH group will form an anion and attach to the positive ion in the base.  Say you used KOH.  So when it hits the eugenol, the K attaches to the now bare O in the former -OH at the 4 position.  But will the base also break the ether bond of the 3-methoxy group?  If only while in solution?  That's what terbium's hoity-toity alkali fusion synth is doing, right?  So this will have formed basically two KO groups at the 3 and 4 positions, right?  So whay can't a solution of eugenol and KOH (or NaOH) and eugenol in DMSO be dripped directly into DCM to form safrole?  Will the free Me group inhibit methylation?  Will the MeO ether bond never break in the first place?
It means 'The Fox' in Spanish

[Rhodium]

No, basic fusion will exchange the methoxy for a hydroxy through the SN₂Ar mechanism (also called NAS, Nucleophilic Aromatic Substitution).

[ClearLight]

  How about using some of the biotech de-methlyation enzymes?  is this a possible modality???

Infinite Radiant Light - THKRA

[Rhodium]

That would be too involved and expensive per mole, I think.

[SPISSHAK]

Acid clevage of the methoxy for example zinc chloride and a hydrohalogenic acid, HCl for starters, why would'nt that system work to break a methyl group (I understand that hx elimination would have to follow).

[GC_MS]

Working with enzymes certainly is not involved (at least if you can calculate a pH), but it is very expensive   . But who knows what the future brings the grandchildren of todays bees. They might work with genetically modified bacteria that can produce day and night, week after week, 12 months a year the same amphetamine derivative.... Damn, this is a very interesting dream   .
-[ A Friend With W33D Is A Friend Indeed ]-

[El_Zorro]

So even if you added an excess of base in order to form a KO complex as soon as the methoxy was substituted with the -OH?
Who is that masked man?

[terbium]

Acid clevage of the methoxy for example zinc chloride and a hydrohalogenic acid, HCl for starters, why would'nt that system work to break a methyl group (I understand that hx elimination would have to follow).
Lewis acid should also work, this has been discussed here and even tried. If you UTFSE and search for references to "eugenol" (without the quotation marks) you will find this. The biggest problem is the reactivity of the demethylated eugenol, it easily oxidizes, and perhaps even undergoes other reactions, to form crud and this seems to happen best in acidic environments. Solutions of demethylated eugenol especially aqueous, acidic solutions will need to be handled under an inert atmosphere.

Another reagent that has been used to demethylate eugenol is pyridine hydrochloride and there are some threads here about that. One procedure using pyridine hydrochloride that is discussed here sems to give good yields. The biggest problem is that pyridine stinks and is not OTC.

[tiresias3]

The best (only practical?) thing to do with eugenol is to methoxylate (ethoxylate if you'd rather) the 4-position and go from there IMO.

[El_Zorro]

But it's just sooooooo close to safrole, there's gotta be a high-yielding one stepper, there's just gotta be!

I still think that applying the same methylating procedure to eugenol that is applied to catechol and the like should give at least some safrole.  I might very well be wrong, but hear me out.

Alright, in terb's alkali fusion synth, they add the KOH, and it breaks the ether bond in the methoxy group, and forms two KO-R groups.  Now, they said they added HCl at the end of the reaction to prevent a black tar formation.  Now, doesn't this sound like they added the HCl, and it reacted with the KO-R groups, forming two HO-R groups before the acitvated KO-R groups could react with each other and form the dreaded dimers and trimers.  So this would mean that there would be two active KO-R groups on the molecule, just like there would have been if one had started with two HO-R groups in the first place.  So why can't the DCM latch on here?
Who is that masked man?

[moo]

But it's just sooooooo close to safrole, there's gotta be a high-yielding one stepper, there's just gotta be!

Go on, be a pioneer.

[Rhodium]

4-Allylcatechol

To a solution of 11.5 g (0.07 mol) of eugenol in 30 mL of dry THF was added stepwise 2.1 g (0.07 mol) of a dispersion of NaH in oil (80%). After the evolution of gas had stopped a solution of 13.4 g (0.07 mol) of LiPPh2 in 60 mL of THF was added. After stirring for 3 h, 2 mL of water was added and the mixture was poured into 200 mL of degassed 0.2 N aqueous NaOH. The yellow solution was washed with ether (4x). and the combined organic layers were extracted with 100 mL of 0.2 N aqueous NaOH. The combined water layers were acidified with concentrated HCl to pH=6. The resulting emulsion was extracted with ether, and the organic layers were washed with water (5x), dried (MgSO4), and evaporated to dryness. Purification by column chromatography (eluent: 2% MeOH in CHCl3) gave 5.97 g (57%) of a brownish oil which could be further purified by sublimation. A yield of 3.9 g (37%) of 4-allylcatechol was obtained as a bright white solid.

[ChemisTris]

What about "silicon tetrachloride/sodium iodide as a convenient and highly selective regioselective ether cleaving reagent."?
Got democracy?

http://www.dhushara.com/book/multinet/democ/wed.htm

[Rhodium]

Can you post that? I don't have "Synthesis" access...

[ChemisTris]

I actually did a literature search and 2 refs came up. This synthesis one, and the one you posted Rhodium.

In the article the cleave a bunch of ethers and note that "It was found that the use of iodotrichlorosilane is compatible with compounds containing double bonds..."
Yields were between 11% - 80%.
R² = OCH₃
R⁴ = H₂C:CH-CH₂-
Method B: 67% yield, 20 h relux.

Edit Oops, i left out the better example    a bit distracted sorry.

R¹ = OH
R² = OCH₃
R⁴ = H₂C:CH-CH₂-
Method B: 62% yield, 20 h reflux

Note: the silicon tetrachloride and iodide salt is forming iodotrichlorosilane.

Cleavage of ethers with silicon tetrachloride/sodium iodide; typical proceedures:
Method A: Allyl phenyl ether (2.68 g, 20 mmol) and sodium iodide (3.3 g, 22 mmol) are dissolved in 1:1 dichloromethane/acetonitrile (20 mL). Silicon tetrachloride (2.5 mL, 22 mmol) is added from a dry syringe and the mixture is stirred and heated under reflux for 8 h. The mixture is then hydrolysed by pouring into water (50 mL) and extracted with ether (2 x 50 mL). The phenol is extracted from the ether layer with 10% sodium hydroxide solution (20 mL), the extract is acidified, and extracted with ether. The ether is evapourated and the phenol obtained by distillation of the residue; yield: 1.56 g (84%); one spot on TLC (silica gel, 1:3 ethyl acetate/hexane).

Method B; o-Dimethoxybenzene (2.76 g, 20 mmol) and sodium iodide (6.6 g, 44 mmol) are added to 1:1 acetonitrile/toluene (30 mL). Silicon tetrachloride (5 mL, 44 mmol) is added and the mixture is stirred and heated under relfux for 12 h. Catechol is isolated from the reaction mixture as described in method A.

SiCl₄ is not OTC, but the yields are at least resonable. Has this not been discussed before?

Got democracy?

http://www.dhushara.com/book/multinet/democ/wed.htm

[Neron]

See:

Post 369637

(Neron: "SiCl4", Chemistry Discourse)

I think this could use a lot more discussion.  If it was within my ability, I'd be experimenting on this right now, instead of just researching it.

Looking forward...
Can placebos cause side effects?  If so, are the side effects real?

[lab_bitch]

Instead of trying to remove the methyl group in one step and add the methylene group in two steps, why not combine them.  Etherization by condensation of two alcohols is a reversible reaction.  Al2O3 is a good catalyst for condensation of two alcohols.  If you dissolved the eugenol in a solution of methylal containing dehydrated Al2O3, the catalyst would catalyze the exchange of the alcohol group with an acetal.  I don't know which product the equilibrium favors more, but if it favors the methyl group, a method of removing the methanol would drive it to completion.  The only problem that I forsee is the addition of methanol across the double bond, catalyzed by the Al2O3.  This can be easily avoided by first oxidizing the eugenol to the ketone and using it in this reaction.