Author Topic: Has psychokitty won the OTC safrole contest?  (Read 13299 times)

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psychokitty

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Re: More on the AlI3 trial
« Reply #20 on: October 25, 2000, 02:09:00 AM »
You can make your own I2 from VERY OTC chemicals (sulfuric acid, NaI, and potassium permanganate are heated together, diluted with water and the I2 extracted with solvent; haven't tried it though).

Still don't understand what you are saying about the hydrolysis.  Are you adding dilute HCl or does the use of a PTC eliminate the need for this?  And at what point does the aluminum precipitate?  After the reflux step using the PTC? 

Anyway, to get around the aluminum filtration problem, all you have to do is add dilute HCl whenever it's convenient.  This forms aluminum chloride which will fall into the lower aqueous layer.  The goods will be in the top solvent layer (toluene was a very good choice, BTW).  Dry, evaporate, and see what you get.  If the stuff is crystalline, it's a good bet that it's what we want.  If it's an oil, just wait.  It will probably crystallize soon.  If you have ferric chloride, add some to the suspected allypyrocatechol in  alcoholic solution.  This should form a green color reaction.  Otherwise, check the melting point.  You don't have to use a small itty-bitty sample to do this (which would be hasslesome).  Put some (or all of it, if you wish) in a glass container heated slowly in an oil bath.  If the stuff all starts to melt somewhere in the 48-50 deg C area, you might be good to go.

Keep up the good work.  SWIM will start up his trials soon.

--PK

startinout

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getting there
« Reply #21 on: October 27, 2000, 07:24:00 AM »
After adding the combination of eugenol/PTC/bitofsolvent dropwise to the stirring but cold AlI3 suspension the mixture was refluxed for about 30minutes, then cooled to about 5C with lots of stirring to stop the suspension settling, then the entire mix was poured into 2M HCl (i was doing a 19.2g eugenol trial and dumped the whole thing into 200ml acid), vigorous stirring was applied for a five minutes then the mixture left for the layers to seperate, three layers formed, a  bubbling water/grey suspension layer on the bottom, the bubbles were dragging some of the suspension to the top were they would promtly fall back down. The top layer was the cyclohexane (oh i changed solvents for this trial) and inbetween the two layers was a black crystalline mass with specks of red in it. The bubbling continued for some thirty minutes (it was not solvent boiling off as the mix was only warm to touch and anyway it was generated in the lower water layer not the solvent layer), i don't think it was Me-I (bp?) so what was the mystery gas???
Anyway after the gas had stopped i filtered off the mass in the interface, separated the layers and removed the solvent, the cyclohexane had a small mass(~2g) of black gooey tar dissolved in it, the water when evporated on a water bath (my rot evap is fucked) produced a white crystalline mass on top of the water as the water evaporated (ie allylpyrocatechol is sparingly sol?, the water/air interface is cold enough for it to crystallise, i am clutching at straws?), I then went home because it was late and i was tired and had an exhibition to go to, then i went to this bar and meet this girl that i had spoken to a few times, she was nice, we chatted, she bought me a drink, we went to another bar, we played with each others hands, we kissed, we went back  to her house, oh yes the workup, when I got back in in the morning the white crystalline mass had turned black and tarry and the whole thing looked shot. Whilst doing a vacuum distil I got hungup on the IR and forgot about it, it was rather a sorry mess when i got back there, but i could see the presence of some of those purpley crystals which i think are the Al-goodbit complex. Anyway will start again tommorrow after that fuckup.
Also though, i ran a trial using iodine and aluminium foil (cut in thin slivers) instead of the 5micron aluminum powder i was using. the foil worked fine.
Has anyone tried using HI to cleave this bastard, you could form it insitu from the insitu created AlI3 by keeping the mix cool (ie don't go to reflux) and dropping water in.
Anyway will try again another day, i need to do some legit work next week, don't have any safrole at present so I have to wait for the RuCl3 and catalyic converter trial on the benzo wacker, good luck mr/mrs/miss/ms/dr/prof/rev/mc/mp kitty-man, crack it next week so i can move on to the methylene bridge reaction, i am bored of the cleavage shit.

Sorry just re-read your post there are some problems with the ease in which you describe the workup, firstly the organic layer also has residual iodine in it, secondly the allypyrocatechol has some solubility in water.
Basically what happens when you make the AlI3 is that you mix the iodine/al/solvent at room temp the whole thing goes bright purple, you then reflux and stir for a couple of hours, the solution goes clear with a finely dispersed grey suspension wizzing around, next you need to cool it in order to add the eugenol, cooling  seems to decompose some of Ali3 and the solution turns reddy again, then when you begin to add the eugenol the whole things turns dirty orange but for some reasom the iodine after hydrolysis wants to stay in the organic layer (is this normal?), giving it a red colour.
A further point, sorry this is a very long post, someone gave me a demethylation method where the aryl ether is dropped into a ALCl3/NaCl (5:) melt at about 150C, left for about three minutes then dumped into icewater, its all done under N2, anyone had any experience with this reaction, it sure sounds quick and easy. Yeah you say a quick and easy way to make tar.
OK I am going now



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Osmium

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Re: getting there
« Reply #22 on: October 27, 2000, 03:15:00 PM »
I wouldn't expect the phenol to be very soluble in cyclohexane. That black shit layer could be your product.

Lilienthal

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Re: getting there
« Reply #23 on: October 27, 2000, 06:36:00 PM »
The mystery gas is H2 from the reaction of excess Al with HCl. I also think that the product is unsoluble in cyclohexane. I would extract the product from an aqueous phase 3 - 4 x with ethyl acetate. Additionally I would use Al foil instead of powder and no HCl. The product is possibly very sensitive to strong bases and metal ions / H+.
>  the iodine after hydrolysis wants to stay in the organic layer (is this normal?)
Yes

startinout

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Re: getting there
« Reply #24 on: October 28, 2000, 05:38:00 AM »
Thanks for the input people, i will do the reaction again, hydrolyse half with water, see what products i get, if they are similar i will extract the black crud with 4x Ethyl acetate and see what i get, if they are not similar i will hydrolyse the remainder with the normal 2M HCl and still do the extractions.
Does anyone know what color the pyrocatechol is supposed to be?
Also i have in my possesion 15kg of anhydrous AlCl3, can anyone suggest something to do with it???It was free so i don't mind wasting it.


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psyloxy

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Re: getting there
« Reply #25 on: October 29, 2000, 02:11:00 AM »
What about this, looks easy enough to try :

"Eugenol and vanillin were both demethylated by cooking with either 5% NaOH or 5% Na2SO4, 1% NaHCO3 and H2O. The degree of demethylation is not given in the abstract but it is in the paper which luckily is in English if one cares to look it up. The reaction does proceed slowly"

Hayashi and Namura, Nippon Mokuzai Gakkaishi 13, 24-27 (1967)
Chemical Abstracts 67, 4500z (1967)

--psyloxy--

terbium

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Re: getting there
« Reply #26 on: October 29, 2000, 04:21:00 AM »

"Eugenol and vanillin were both demethylated by cooking with either 5% NaOH or 5%


There are lots of ways to perform the demethylation. The problem is that most of them will also either isomerize the double bond to form the isosafrole precursor or add halogen to the double bond. Cooking with NaOH for long enough to demethylate should also isomerize the double bond.


psyloxy

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Re: getting there
« Reply #27 on: October 29, 2000, 09:45:00 AM »
>Cooking with NaOH for long enough to demethylate should also isomerize the double bond.
Nothing bad with that IMO. Performic rulez!  :P

--psyloxy--

startinout

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Another long post
« Reply #28 on: October 30, 2000, 01:55:00 PM »
Yields for demethylation via a caustic route have always been ordinary, which in this case would be tolerable as eugenol is cheap and in plentiful supply. the real problem is that via the caustic route you end up with re-arrangements. Any trained chemist writing the mechanism on paper can see the potential for nucleophillic attack by not only the hydroxyl but by the liberated methoxyl groups. The resultant re-arranged products are very difficult to separate from the product you want as they are often isomers or chemically similar.
Face it, if it was as easy as boiling up some eugenol with NaOH to faciliate a servicable demethylation reaction then why would their be so many more exotic patented methods published. Why would industry waste money on anhydrous AlCl3 methods. The reality is this is not an easy reaction and no method currently seems to be fool proof enough for scaling, that is why there is so much discussion regarding this issue
Has anyone read the demethylation route via AlCl3 and pyridine. The problem with this method is the workup needs to be adjusted. I have tried it a couple of times and always gotten muck, probably because of the Al/H+ issue in the workup. Are their any organometallic/inorganic chemists out there who could enlighten us on the nature of olefin-Al complexes, how strong are they, how do they decompose etc. i know I could look it up but at present I simply don't have the time as my mom is quite ill. Any help would be appreciated.
One more thing does anyone have any material data on the demethylated/isomerised eugenol product.
Thanking you all in advance for your help
bye bye buy buy


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startinout

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demethylated eugenol
« Reply #29 on: November 04, 2000, 07:22:00 AM »
The product from the fabled demethylation of eugenol seems not to have too much attention in the literature. Some time ago someone posted some data on this compound, the mp, bp and some solubilities, thanks very much for this data. Now what i really want to know about is it's stability, in air and light. Seems to me that whenever I leave the unworked-up product for any period of time the whole sheebang goes from looking rather clean and discrete to looking shitty, any ideas(?), maybe I should be less lazy and do the reaction through to completion.
Anyway lets not drop the ball on this method, eventually a servicable method will appear, so keep vomiting up your ideas one and all.



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Osmium

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Re: demethylated eugenol
« Reply #30 on: November 04, 2000, 09:54:00 PM »
Most phenols are easily discolored by oxidation. Just because it changed appearance doesn't mean it's unusable. Store dark and air tight.

Beaker

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Re: demethylated eugenol
« Reply #31 on: November 05, 2000, 05:27:00 AM »
1,4 and 1,2-diphenols are readily oxidized to the corresponding quinones. Keep it away from air.

startinout

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Re: demethylated eugenol
« Reply #32 on: November 05, 2000, 08:47:00 AM »
OK so it's easily oxidised, any idea how easily. benzoquinone hangs around for a while in light and air, but that is a 1,4, would a 1,2 oxidise far more readily?
Pyrex is opaque to UV so if we were to work under N2 in pyrex we shouldn't have any problems should we (unless of course visible light is a problem??)
I will now retry the pyridine/AlCl3 method under n2 to see if the results improve, will keep posted.
Thanks for the advice


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startinout

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Success, finally
« Reply #33 on: November 10, 2000, 11:58:00 PM »
Well I have a solution of 4-allyl catechol in ethyl acetate, great huh.
How it was done, i will give proportions
1mol Al turnings (or foil or powder all work well, powder is the quickest closely followed by foil then turnings a distant third) is combind with 1.5mol (note the excess of Al) of Iodine in 1000mL of cyclohexane (exchange solvent as needed but not ether!!!!!). This mix is stirred under reflux until the red colour has turned to a grey (about 1.5hrs with powder, 2-3 with foil, 4+ with turnngs). At this point the heat is turned off and the AlI3 in solvent allowed to cool to room tempeature with stirring. in a dropping funnel, eugenol (1mol), tetra n-butyl ammonium iodide(1/360 mol) and a little cyclohexane are combined. This is slowly dripped into the AlI3/cyclohexane with vigourous stirring and inert gas sheilding. After all the eugenol has been added the solutiuon 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.
The resultant mix is filtered under nitrogen and the solid collected immersed in ethyl acetate, this is swirled for a couple of minutes, then filtered. The ethyl aceate is seperated from the water (collected through the filtration) and removed and what you have left is a tan coloured solid with a charactistic 'smoke' smell and a melting point 45-51, althought this range could be tightened by recrystalisation or vac distillation with hot water in the condenser.
A few notes
-If you are quick then maybe you can not bother with the inert atmoshpere in the workup, however the filtering takes a long time (don't even consider using gravity) beacause the Al is very finely divided and clogs up the filter paper.
-it seems the reactant ratios are critical so get them right.
-The workup is a shit for large quantities, any suggested impovements would be appreciated. Note particularily that the next step (adding the methylene bridge) requires the catechol to be dissolved in DMF, so we need to figure out a way to end up with the 4-allyl catechol in DMF.
looking forward to your suggestions.




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Rhodium

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Re: Success, finally
« Reply #34 on: November 13, 2000, 03:32:00 PM »
What kind of yield did you get?


http://rhodium.lycaeum.org


startinout

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Re: Success, finally and failure again
« Reply #35 on: November 14, 2000, 12:45:00 PM »
The stuff was black and hard when i got to it the next morning, this reaction is really iritating me, the workup is simply not scaleable. have an idea though for using some hydroquinone in the AlCl3 demethylation to try to halt the black tar factor from fucking everything up, will post results. but for the record don't bother as yet with the previously mentioned AlI3 method, unless you are of course trying to help me develop it.
But some good news, well i think it is good news, let me know what you think, vanillin is demethylated by the AlCl3/Ch2Cl2/pyridine method set out by Lange in 1962 (can't remember the journal but the reference is mentioned earlier in this string, 87% yield). Good thing is the method is set out for vanillin and we are not making assumptions by adjusting the method for eugenol.
The demethylated protocatechualdehyde is then methylated to piperonal using the reported (yes they did it on actual protochatualdehyde, 90% yield) method of Cark et al, the reaction takes 1hr, no inert atmoshpere, just mix your protocatecualdhyde with KF add DCM, reflux at 115 for 1hr and extract.
Now the thing question is---- is piperonal a known, ie a known, ie ie ie a fucking known, as has anyone actually performed the reaction type known (sorry for the dissenting attitude but there is far too much speculation masked as reality around), precursor to MDP2P via the knovenagel reaction with nitroethane and reduction with Fe and HCl or Al etc, if so please post the entire method somebody or some weblink to it (I have used the search engine here and looked on Rhodium if it is there i am blind).
Once I am convinced that piperonal is a useful precursor to aspire to instead of safrol from eugenol then I will go ahead and try the above mentioned synth as I have all the neccessary bits and post my results. Again apologies for the threatening tone, not meaning to get aggressive, it is just late and the batteries on my blow up wife are spent, sick of this oppresive governmental regime I live under and woe-est-me-to-the-enth-degree
Anyway hopefully someone/anyone/please someone/please anyone/ hey you over there yes you please post, will post
But for now good night


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Rhodium

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Re: Success, finally and failure again
« Reply #36 on: November 14, 2000, 09:28:00 PM »
Look in Pihkal #100. Shulgin condenses piperonal with nitroethane and reduces the nitropropene with Fe/AcOH to MDP2P. It works.

If you use CH2Cl2 and K2CO3 in DMSO as in TSII for your methylenation of protocatechualdehyde, it will be a lot cheaper and less toxic than using KF et al.


http://rhodium.lycaeum.org


startinout

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Re: Success, finally and failure again
« Reply #37 on: November 15, 2000, 12:28:00 AM »
thank-you for your reply Mr/Ms Rhodium,
In my country it is very difficult to obtain TSII, I brought back shulgins book when i went to the US on a conference so i can access them, if it is not too much trouble could you please post or email me the DMSO/K2CO3 method, just the basics. i am beginning the vanillin route today now that i know the piperonal method will be effective, the demethylation takes 24hrs, will post results as per usual.
just a note do you think polar aprotic solvents would interact with AlCl3 more stongly than the aryl ether (ie would they complex preferrentially over the ether). if not then the demethylation can be performed in DMSO/DMF  and then the demethylated product can be rrun straight into the methylene bridging reation without having to strip off solvent under n2/out of light etc. Just a thought, would appreciate input, will look in Feiser. But i will do the method straight out of the paper first but our goal is to design a synth that can be easily perfomed at home with OTC chemicals, then i get the $1000, right, I think it will end up being split eighteen ways perhaps.
Back to the lab

Bliss is a disinterested supervisor


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startinout

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Let's be realistic
« Reply #38 on: November 16, 2000, 04:49:00 PM »
The double bond in eugenol (the one on the side chain) is electron rich, much more so than the oxygen on the arlly methoxy ether. hence any electrophile one sends to establish contact with the methoxy/ether oxygem will invariably get side tracked to the side chain olefin. Thus unless one converts/deprotects the methoxy ether it will be difficult to cleave it.
it is amazing to see how simple it is suspend AlCl3 in vanillin compared to how difficult it is to suspend it in eugenol.
Let us focus our attentions on the deprotection of the methoxy, any ideas?????????
Again, in the words of Madonna, let's not drop the ball.


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psychokitty

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Re: Let's be realistic
« Reply #39 on: November 17, 2000, 05:34:00 AM »
Do you mean to imply that the allylpyrocatechol which you have isolated about twice wasn't allylpyrocatechol to begin with?  Or does it simply decompose readily before you have a chance to use it?

Why don't you simply go the route of biphasic DCM/PTC/catechol compound/NaOH/dH20 to effect the required methyleneation?  It would be easier, less hasslesome than the DMF/KF/DCM reaction which requires anhydrous conditions.  Information on how to conduct this reaction under pressure are detailed on Rhodium's page.  But I do have a reference to a Tettrahedron Letters article wherein the reaction is performed at room temperature.  SWIM has performed the DMSO methyleneation on catechol to get benzodioxole in about 60-65% yields -- being sloppy, that is.  Although it was very VERY easy, I doubt this method is suitable for allylpyrocatechol or protocatechualdehyde.

I recently saw a chemistry paper online detailing the cleavage of aryl methyl ethers using only pyridine hydrochloride and the ether nuked at low temperatures in the microwave (conventional) for about 16 minutes.  Yields were high and this was performed in a solvent-free environment.  Might be worth a try. 

Another suggestion is to find a way to form MVK first, and then go on to the cleaved product.  This might avoid the decomposition product that you seem to be getting over a short period of time.  Any nitrite wacker fans out there willing to try eugenol in your reactions?

I'll get you that reference soon.

--PK