eugenol --> (iso)safrole

Soap · Sun Apr 03, 2005 7:40 am

well swim is having problems recieving his sassafras oil. the place he buys from keeps sending the oil but it never arrives... so swim is going to order some clove oil. There are numerous methods for changing eugenol into safrole but swim is unsure of which one he should do. he really wants to arrive at mdma via the iso--->performic--->al/hg method. He has moderate experience in the lab, synthed gbl from gaba made ---- a few times, but nothing more than that. which method should he use? otc chemicals are (of course) ideal as well as limiting the amount of lab glass required. Swim would love to write up a step by step guide with images once he completes this (and he will) thanks for the help!

Guest · Sun Apr 03, 2005 7:51 am

It is such an abundant Oil, and it could certainly be used for production of isosafrole,

This would be a very exciting method to perfect, and look forward to a good practical synthesis in the future

syn

ApprenticeCook · DILLIGAF

them sending the oil and it not ariving is a screw up once, but more than once its occured? not a good sign....
Just take care with what you do.

As for eugenol --> safrole best method for demethylation is so far AlI3/PTC but the PTC is the problem, aswell as the requirement for an inert atmosphere, argon is easy enough to get but the glassware to do it, as you said you want a minimum requirement...
If you can find an appropriate PTC, PEG-400 i was told isnt to hard to get and may work in place of TBAI which is a bit hard to make but certainly do'able... Bu4NI = Tetrabutylammonium iodide (TBAI)
3Butanal + NH3 --> Bu3N (+ BuI -->acetonitrile--> Bu4NI)

-AC

Soap · Sun Apr 03, 2005 9:24 am

Swim actualy orderd the sassy (very carefully) but it never came, so after contacting the company via secure email, they agreed to send out another 4 ounces.

it looks like the method you shared is the most likely for swim to succesfuly use. The two problems, like you said, are the need for a phase change catalyst as well as an inert atmosphere. swim did some quick reading and it seems there may be useful PTC's in hair conditioners. swim is sure there is an easier way to come about aquiring a useful ptc and will continue his search. argon is very easy for swim to aquire, however swim already has plenty of CO2, would that suffice? what type of lab glass is required for this reaction? swim has a ground glass vacuum distillation set up, could he use that to contain the gas? how do you release pressure? does anyone have hands on experience wiht this method?
thanks!

Soap · Sun Apr 03, 2005 9:35 am

of course seconds after posting swims reply it was realized that peg 400 can very easily be bought, i guess its also callled carbowax (sorry if swim is naming sources). swim assumes now the only hurdle is containing the inert gas and im sure the awnser is soon to be found. is it really this easy?

capricorn · Sun Apr 03, 2005 2:07 pm

If one were to substitute vanillin for eugenol in this reaction http://www.orgsyn.org/orgsyn/prep.asp?prep=cv3p0745
wouldn't it be posible to arrive directly at 3,4-dihydroxypropenylbenzene.
I mean, woulden't KOH isomerize eugenol to isoeugenol also, like in the standard isomerisation reaction?
Demethylation and isomerization in one step is convenient. Just a methylenation from isosafrol if it works. Smile

ApprenticeCook · DILLIGAF

PTC = phase transfer catalyst, not phase change...

For this reaciton dont just dump in some hair conditioner.... you wont get anything but a clumpy mess at the end, you need to procure a suitably purified supply of a PTC, you only need catalytic amounts so as per the TBAI method i described even though the yields are quite poor you can still make a suitable amount for heaps of demethylations... for a cheap price...

CO2 isnt an inert gas, yes it can be subst in some reactions but this one is very particular to oxygen and most CO2 cylinders have quite an amount of oxygen contamination.... buy the argon, make sure its not argox, this is an oxygen mixture... buy straight argon and use that, its cheap.
To do this reaction a reflux set will suffice, you need a pressure equalised addition funnel and cone-tube adaptor to hook up your gas line.
The best way i have found is to hook up a Y adaptor to the cone-tube adaptor, one end leads to the argon cylinder and the other to your vacuum source, evacuate the entire apparatus with reagents inside to a decent pressure (~15"Hg should be fine) then turn off the pump, leave it all connected and then pump your argon in by turning on the cylinder, pump it till the pressure in the aparatus is back to normal air pressure (0"Hg), argon is heavier than air but still mixes quite well with it, so the vacuum helps reduce this, and provide better inert atmosphere conditions.

If you ask a specific question about the procedure we can help.
I dont know how substituting the PTC PEG-400 instead of TBAI will effect yields but i doubt it should be a large issue...

Capricorn, doesnt sound to bad but not sure how it would work with eugenol, may work but dont know, y dont you get some and give it a whirl? let us know, you could be a cladestine pioneer!
But to me its a bit of a pain, the high temps, req to pump SO2 in copious amounts (i dont like SO2, my lungs are bad enough) makes it risky... what would you do with the SO2 vapours released?

-AC

IndoleAmine · Dreamreader Deluxe

Eugenol is OTC as "clove oil" in most pharmacies around the globe (~80% eugenol content) - they just don't like selling it because it stinks... Wink

i_a

IndoleAmine · Dreamreader Deluxe

java · Consumer

The topic of eugenol conversion has been discussed at the old board also, here is a thead on it and their findings, as I hope it will add to the discussion ........java

Ref: Old Hive board

[psyloxy] Eugenol --> X again
01-26-2000 06:08 PM

Hey bees ! Let's open up this 'HOW THE FUCK CAN X BE MADE FROM EUGENOL' thing again! Oh no - not again you say ? Shit. Cause then I really don't know what we do if they make sassy oil illegal (like in some countrys around where I live). You may say that sassy oil can still be distilled ... good luck. [could as well imagine being on X - would be as hard to do]. Other alternatives ? Vanillin --> piperonal ?

Well if nitroethane wasn't that fuckin controlled... but if there was a way to it - why not. Catechol --> Benzodioxole --> .... of course with an overall yield of 1%. Other suggestions ? Say what you want but I think eugenol is cool. So lets discuss its conversion to something more useful. Here are some parts of past postings :

clove oil = virtually ALL eugenol....
Oil of cloves is usually about 85% eugenol and is easily extracted without the other shit coming with it!! In summary, however, there don't seem to be many viable ways to cleave eugenol's methyl ether bond while in the presence of the allyl side chain. But there are SOME methods that seem to have potential. Most likely, however, the ketone (MVK) will have to be formed first. Then the ether bond can probably be cleaved.

I have no record of this having been tried with microwaves and that might be a solution as well. So 90 parts AlCl3, 10 parts AlI3, 3 parts quat salt [thats a PTC ?] and anything between 90 to 33 parts of Eugenol microwaved on a clay support. If too much AlX3 then the methoxy will react with the ring to give a more substituted ring. If too little AlCl3: not all the eugenol will be converted. you have ended the debate about whether or not HI alone OR with a PTC can cleave eugenol's ether bond successfully. The answer: IT CAN'T

But it can be done on MVK

For your information, H2SO4 indeed can be used to cleave that OMe. Hey Wizard got the file

--A small scale real dream [XFile8]
I think you would do better to demethylate the eugenol using anhydrous AlCl3 in a solvent like tetrachloroethane. This would produce 3,4-dihydroxy-allyl benzene (allyl-catechol) ...demethylate, A mixture of 95% AlCl3 and 5% AlI3 with PTC, in DCM looks promising to me

First the Eugenol could be demethylated and halogenated to 1-(3,4 dihydroxy phenyl)-2-bromopropane with aq. HBr and a PTC catalyst (Aliquat 336 is king).

I remember a paper where the different MeO-phenolethers were hydrolysed with aq. H2SO4. The p-MeO was hydrolysed fastest of all, the m-MeO was intermediate and the o-MeO was hydrolysed slowest. Eugenol polymerizes when exposed to concentrated H2SO4 -- even at zero degrees. I have an old review of sulfuric acid addition to olefins which SPECIFICALLY details this. I know safrole is on that list as is, I believe, isoeugenol.

Concentrated H2SO4 won't work, that's obvious. But what about 40-50-60%? Of course this will work, BBr3 is the king of ether cleavage reagents in my book.

OTC Safrole Synth Contest, Part II
Aluminium Triiodide: Aluminium powder (2.5 g, 93 mmol) and iodine (19.0 g, 150 mmol) are mixed and refluxed in benzene (120 mL) until the red colour of iodine has disappeared (1.5 to 2 h).

Other possible demethylation agents are LiI, KF. KOH seems viable Here is a simple, high-yield method. And when reading the original article, I see no reasin why the procedure couldn't be applied to eugenol, to give a starting material for making your own safrole.

['Vanillin to protocatechualdehyde']
Anyone tried Wizard X' method ? MVK (thats 3,4-di MeO-P2P right ?) ether cleaveage, or : what to convert the eugenol first into ?

Think of eugenol-methyl-ether. tread it like safrole; could the ether-blabla be easier to do with 3,4-di MeO-MA ? [or in general : is it useful to have 3,4 di MeO instead of 3-OH-4-MeO ?] And the most promising (I hope): a-Me-Dopa . Eugenol-methyl-ether (or somethin made out of it - dont know for sure ) is said to be an important intermediate for the production of a-Me-Dopa. I think if one would look up a synth for this special compound one would find intresting stuff.

Any ideas how to trade 3,4-DMA to get somethin useful ? maybe adding halogens or the like ...

Lets end this post with a final thought:
"Eugenol IS cheap, and I don't really care if the yield of sassy or any other precursor from eugenol is 20%, as long as the synthesis involved is cheap, fast and easy to do. " - Osmium

...and let me add some of my personal thoughts to this:

*I* don't care if this is OTC or not. I dont live in da USA. For me P4 is 20$/100g and the I2 is 75$/500g [but crystal really is a shitty drug and I will never dream of using these two in ... u know what...(really)]

And I dont even care if it makes the procedure 5 steps longer. For me it is important that everything runs cleanly . And I *hate* knowing that drugs really can be and ARE manufactured with fucking drain cleaners. Well - so if I loose 30% of product in every step, then I have 15g MDMA from 100g Eugenol or maybe 200g. But WTF 15g thats 150 pills - lasts some ten years for me (yeah, I know I'm a looser cause I don't eat 10 per weekend).

--psyloxy--
I'm somewaht agressive today - ignore it ; and keep : )'in

Wizard X
PimpBee posted 01-26-2000 06:40 PM

psyloxy: The problem with AlX3 demethylating reagents is the fact that Friedel-Craft Alkylation will occur. Another way is to react eugenol with Br2 to saturate the -HC=CH2 bond, and then demethylate with HI. Refoming the double bond with rearrangement to a propenyl arrangement.

Wizard X
PimpBee posted 01-26-2000 06:53 PM

Other possible demethylation agents are LiI, KF, KOH seems viable. BBr3 is the king of ether cleavage reagents. If you saturate the -CH=CH2 with Br2, then KOH can not be used. Finally, convert the eugenol to an amphetamine firstly, then demethylate with BBr3 or HI.

Cherrie Baby
Hive Bee posted 01-29-2000 06:13 PM

I don't see why Friedel-Craft Alkylation has to occur with AlX3. If you keep the AlX3:Eugenol ratio at no more than 1.1:1 then Friedel-Craft Alkylation should be minimal.

psyloxy
Hive Bee posted 01-30-2000 04:51 AM

Eugenol to 3-MeO-4-OH-[----]Amphetamine should not be that hard to do. Yust the way you would go with sassy.

But when demethylating with HI (or in general) what happens to that CH3-O-I that is formed (if it is formed)? Doesn't it react with an HO- again ?
--psyloxy--

Rhodium
Pimp Master posted 01-30-2000 03:43 PM

Methylation is not favorable in a strongly acidic solution, only demethylation is.

psyloxy
Hive Bee posted 01-30-2000 08:25 PM

Forgive me that CH3-O-I of the last post, I should not stay up that long. But doesn't the HI interfere with the OH- ? Probably not but I could not resist to ask.

Wizard X
PimpBee posted 01-30-2000 08:44 PM

Cherrie Baby: ZnCl/reflux or FeCl3/-15degC is used to react C6H6 + Cl-CH2CH=CH2 to form the allylbenzene. AlCl3 at -14 degC forms the allylbenzene but then further alkylation occurs with benzene. psyloxy: make the Eugenol to 3-MeO-4-OH-Amphetamine, and then demethylate with HI to form 3-OH-4-OH-Amphetamine.HI

Wizard X
PimpBee posted 01-30-2000 08:50 PM

psyloxy: make the Eugenol to 3-MeO-4-OH-Amphetamine, and then demethylate with HI to form 3-OH-4-OH-Amphetamine.HI + CH3I As Rhodium said, "Methylation is not favorable in a strongly acidic solution, only demethylation is". So the CH3I will NOT methylate the -NH2 to -NHCH3.

psyloxy
Hive Bee posted 01-31-2000 12:39 PM

So when I have the 3,4-di HO-Amphetamine.HI and CH3I in solution (what's the solvent - water ?) I could distill some (hopefully most) of the CH3I out and save for later use. [34DHA.HI crystals or dissolved ?] Then freebase the 34DHA, wash and clean up etc, methylenate (sp? chemical engl is no fun for kraut-boys) with NaOH and CH2Cl2. I think this is where the tried and true part starts. From MDA to MDMA with CH3I at hand should not be too much of a problem particulary because it is well documented. So now it would be of intrest how the step 3-Meo-4-OH-A --HI--> 34DHA.HI is done in DETAIL (althoug now there's a 'Hive Bee' under my name I don't really have that much of a clue on chemistry - but I'm extremely willing to learn and yes I've ordered TSII) Also is there an entry of 34DHA in the Merck ? Uhhm and when starting from the -----amphetamine there should not be any problems (actually one step less)? Thanks a lot.
--psyloxy--

Soap · Tue Apr 05, 2005 9:21 am

swim is goign to attempt to make the safrole using peg 400. is there any reason why anyone would doubt that this will work? swim is just waiting for the rest of his chems to arrive and will try in a week or two.

ApprenticeCook · DILLIGAF

I dont see any reason for it not to work.
The PTC is there to facilitate transfer of ions across the phase barrier.. so as i see it any PTC will do however i would recommend increasing the reaction time just incase the PEG-400 isnt as good at doing its job as the TBAI.

Original:
In a dropping funnel, eugenol (1 mol), tetrabutylammonium iodide (1/360 mol) and a little cyclohexane are combined. This is slowly dripped into the AlI3/cyclohexane mixture made in the previous step with vigourous stirring and inert gas sheilding. After all the eugenol has been added the solution is brought to reflux (it is a tan coloured slurry at this point, but upon refluxing turns less viscous) for 1 hour. The solution is then cooled in an ice bath and hydrolysed with ~600mL of water, slowly.

Modified:
As above but more PEG-400 than TBAI, say 1/100mol or 1/150mol? to make up for the drop in performance (if any) the PEG-400 is easily obtainable and not to expensive is it? and i would recommend refluxing the mixture for maybe 2 hours instead of the 1hour as above... just to be sure.

I havnt had any reports on the use of PEG-400 in this method so i cant comment apart from generalities so experiment and report back to us cause it would prove very usefull....

-AC

CherrieBaby · chouchou

ApprenticeCook · DILLIGAF

PEG-400 is well known, and has the ability to function as a PTC.

Like i said, if you have access to the end product or the precursors to make TBAI as mentioned in the original document then it is better to use it...
PEG-400 as the PTC for the demethylation of eugenol was a topic of conversation back at the hive and it was agreed upon by the majority of the contributors to the thread that it would function correctly in the mechanism of the demthylation reaction. Its worth investigating due to the ease or access and low price of eugenol and peg-400....

Pyridine is very bad for your health (esp fellas) and is in australia a class 1 regulated substance, any sales must be reported so good luck trying to find a source.
Although the method with pyridine is superior it is to hard to access... not to mention how expensive the shit is....

Although if you have any bright ideas on a synthetic proceedure to pyridine then feel free to start a thread about it.... and the method of decarboxylating nictotanamide (vitamin b3? sp?) has been thrashed out to the nth degree so something original please....

-AC

CherrieBaby · chouchou

1) I agree that pyridine is very bad for your health. Methyl Chloride, the likely side-product of the pyridine.HCl demethylation is worse for your health.

The acid cleavage of ethers is discussed on pages 682-683 of McMurray's 4th edn. of "Organic Chemistry" (check out your library, Organic chem course book, or there is a really bad scan available on eMule).

Ethers are notoriously unreactive and aryl-methyl ethers among the most unreactive of all. Acid cleavage can be either SN1 or SN2 depending upon the substrate. With aryl-methyl ethers it will be SN2.

The X- "attacks the protonated ether at the less highly substituted site. This usually results in selective cleavage into a single alcohol and a single alkyl chloride." [McMurry] We know that aryl-methyl ethers are cleaved to phenols and methyl halide. We know that methyl chloride is a poisonous gas and a carcinogen [Merck 13e, entry 6121] In the demethylation using pyridine HCl the fumes should be extracted in a fume cupboard or the reaction done out-doors.

Ar-O-Me + Pyr.HCl --> Ar-OH + MeCl + Pyr.

2) I won't add anything more to the debate about PEG except that I'll believe it works when it becomes a standard, widely accepted, method - not before then. I would substitute any other quaternary ammonium salt I could get in preference to PEG.