peracetic oxidation of asarone to ketone

[goiterjoe]

http://goiterjoe.homestead.com/tmp2p.html

I finally got around to testing this out the other day, and it seemed to work fairly well.  from 20ml of starting asarone, 14.5ml of suspected ketone was returned.  the ketone is slightly viscous with a reddish tint to it.  I didn't wash the aqeous layer from the peracetic part to reclaim the epoxide still in it, so there is the possibility of a better end return from this synthesis.  Does anyone have any experience with using Al/Hg type reductions for amphetamine derivatives?  I was also contemplating making TMMA-2, but wasn't sure about the pharmocological properties of this substance.  has anyone tried this?


If pacman influenced us, we'd glide around dark rooms eating pills and listen to repetitive music.

[blue]

i don't think TMMA2 is very active joe, have alook at randolph carters tma2 synth on Rhodiums page, he details a high yeilding leukart rxn for the ketone >> amine step.

stranger? muahahahaha

[Osmium]

I don't think you made TMA2-ketone. All bees trying this reaction have failed.
How do you know that red goo is ketone at all?

[goiterjoe]

I have yet to read of any bees trying this synth, or otherwise I might have been a little more skeptical about trying it.  I have heard of bees trying the performic route before, but performic is a stronger acid than peracetic.

If pacman influenced us, we'd glide around dark rooms eating pills and listen to repetitive music.

[Dr_Sister]

goiterjoe - actually i'm not convinced it isn't ketone. my reasoning is based on an observation of asarone in GAA while attempting a Toennies style nitrosation and the decomposition product was a blue/purple not red. and it sat in undiluted GAA for 18 hours.

Have you triied a sodium bisulfite test? if you do my experience with 2,4,5TMP-2-P is that is forms a much finer crystal than does MDP-2-P. keep us posted on the reduction.

[goiterjoe]

That was SWIM's reasoning for trying the peracetic oxidation, because he had heard of people letting asarone sit in acetic acid unharmed.  SWIM has had technical difficulties lately due to random carpenters working around the house, and had to temporarily relocate a lab.  (thank god he went through the trouble of sewing up a carrying case for all his glassware and equipment, or he would have been fucked royally when they showed up).  Hopefully he will be able to aminate some in the upcoming couple of weeks if things calm down around here, but for the mean time his nerves are kind of shot.  do you have any suggestions for an amination route that should be somewhat high yielding?

If pacman influenced us, we'd glide around dark rooms eating pills and listen to repetitive music.

[blue]

NaBH4CN redxn (probably highest yeilding)

Oxime via SnCl2 followed by oxime redxn in Al/Hg or with Na (next best)

NaBH4 redxn  (moderate yeild)

Leukart conventional or microwave (hard to say what kind of yeild to expect here)

then there are all those K10 clay redxn's w NaBH4

stranger? muahahahaha

[psychokitty]

The only detailed write-up that I have seen posted for reducing the ketone to the amine is the Leukart (sp?)  The non-microwave-using proceedure, that is.

--PK

[boppesz]

Osmium. Can you explain why asarone can't be oxidized to the ketone with the performic/peracetic acid process? I mean chemically explain. I can't believe that safrole is readliy oxidized and asarone is not. The three methoxygroups dont differ that much chemically from a methylenedioxygroup. Both types of groups are moderately activating. Three methoxys alltogether activate more than a methylenedioxy. So reaction time will be shortened. One thing I can come up with is polymerization. Asarone will polymerize at more ease than safrole. But it will be oxidized at more ease too I thnik (I can be wrong) So I think that reaction times and/or temp should be respectively shortened/lowered so no polymerization will occur But with which factor? I dunno, don't have any experiences with this.

[Osmium]

Asarone dimerizes under acidic conditions. I don't know exactly what the structure of that dimer looks like, seen it once in an obscure ref I haven't been able to find again (didn't look too hard though).
Isosafrole (or was it safrole? shit too many dugs) too can be destroyed by refluxing with e.g. formic acid, but this reaction is slower. This dimerisation business isn't that uncommon.

[boppesz]

Do you have experiences with making TMA2 from asarone? If yes, how did you oxidize it?

[cilliersb]

Just do a pseudonitrosite Asarone (Pugsley or Pseudonitrosite Faq) to obtain the Beta-Nitro compound of asarone. this can be reduced using cyanoborohydride method.

Have fun.

[zooligan]

Just do a pseudonitrosite Asarone (Pugsley or Pseudonitrosite Faq)

Um.... read AntiBody2's practical trials of this process in the Lowdown on Pseudonitrosites thread.  It'll save you a lot of wasted precursors.

z

"And if we don't get some cool rules ourselves, pronto, then we'll just be bogus too!"

[boppesz]

yeah right. And if I don't have cyanoborohydride?

[Osmium]

You don't need cyanoborohydride. Read that thread.

[Dope_Amine]

I say you O2 wack it and then leukart it.  Or if you are able to, hydroaminate it w/ n-buLi cuz it DOES work.
something for your mind.......

[Chromic]

Excuse my ignorance, what functional group dimerizes? Is it the double bond?

[Chromic]

Ok, I UTFSE... and found out that it's an acid catalysed polymerization of the double bond, Osmium said it prior posts that all propenylbenzenes are suspectible (inc isosafrole), but asarone is apparently the most sensitive. Does this mean that a buffered peracid would form the epoxide, and that the epoxide wouldn't be turned into red goo after being hit with 15% H2SO4? This looks attractive. TMA-2 sounds like fun, I want some.  

[sYnThOmAtIc]

Wouldn't electrochemcal oxidation be a suitable means of oxidation?
 The supplies are cheap, reusable, and only requires the starting oil and a couple acids. It is a very high yielding method for sure on the isoeugenl and isosafrole the only ones tested by my monkey (89&93%).   

 Isoeugenol, isosafrole, asarone, anethole, and other similar compounds can be made into their epoxides via electrochemical oxidation and refluxed with Libr for high yields of ketone or just with formic or sulphric acid.

[Osmium]

The "buffered" performic is still acidic as hell, don't think it will work.

That electrochemical epoxidation sounds like a much better idea.

[boppesz]

YES!!!!! Electronic oxidation. Should we start a new forum for this? I think this must be the best way the make the lovely ketones, but there isn't much info on this subject. Is there anyone with experiences with this?

[Antibody2]

i also would like to hear more on the electrochemical route, please elaborate synthomatic.

btw- RC also reported success with the O2 wacker
and i think Dr_Sister also reported a minor sucess with the benzowacker, but there was lots of byproduct if i recall.
"All those memories lost like rain..."

[foxy2]

The electrochemical wacker is on a primary olefin, I doubt it will work on asarone.

I have other refs about PTC mediated wackers(details later) and they only worked for terminal olefins and the electrowack on rhodiums site seems to bee a PTC rxn.
Do Your Part To Win The War

[Chromic]

I was thinking more of the buffered Oxone technique... it is the European root that is desired, correct? I'd love to get it a swing, although it is an expensive oil... I suppose the Leukart would be nice to learn tho.

[moo]

If I recall correctly, they all contain minor amounts of gamma-asarone (the allylbenzene) and the others (alpha and beta) are cis and trans isomers of the propenylbenzene, so it really shouldn't matter. Although I cannot remember which was cis and which was trans, it can be found out using Google.
^{understanding is everything}

[Osmium]

You want the asian/indian/nepalese/whatever oil, that's the 80% stuff.

[Dr_Sister]

chromic - the european variety is the one you don't want.
7.10.01

[uemura]

sYnThOmAtIc,
you said for electrochemical oxidation:
It is a very high yielding method for sure on the isoeugenl and isosafrole the only ones tested by my monkey (89&93%). Any references? Could your monkey make a nice writeup? Everything appreciated Carpe Diem

[boppesz]

I think the ref synthomatic read is the following:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/guest.eugenol.txt

Very very interesting. I'm doing research now on this subject, and after I prepared an electrolytic cell, I will experience, and share my results with yo guys. But this may take a few months.  Another thing: I read somewhere (no refs) that wacker only works on none-substituted propenylbenzenes, so no safrole etc. etc. So skip the wacker and do research in electrolytic oxidation.Let's help each other!!!

[Chromic]

I can't wait to give the Oxone reaction on asarone a try. Hopefully I'll have enough time this year to workup the glycol and do an NMR on a sample.

[sYnThOmAtIc]

No problem. I'll rob him of his notes tonight once the evil professor releases him from the clinic to go to the zoo.

It's no bulshit and it does work. He showed my friend his results in an alley around downtown half past midnight. He told me he plans to do an electroreduction with the resulting residue.

I do know his only references were that of electroepoxidation refs on rhodiums page only. Bee back soon wiht his notes.

Personally I think this is by far the easiest, cheapest, highest yielding procedure which he has showed me.

Plus it is.. COMPLETELY OTC.

Here was the procedure he recreated.

6.5g NaBr from brominating tablets was added to a beaker containing 25ml distilled water. Magnetic stirring is commenced and a mixture of 125ml methyl cyanide and 4.38g isosafrole is added to the beaker and the resulting mixture is mixed for several minutes and a styrofoam faucet cover is placed around beaker to keep a constant temperature. Two small graphite slabs are lowered into solution separated by a stainless steel blade and a current of 1ampre is passed through electrodes for 109 minutes. As the document calls for 2-2.6 faradays per olefin mole and this contains .0263 moles 6597.66 coulombs are passed at 1amp in 109 minutes or at five amps can be completed in 21 minutes. Magnetic stirring is stopped and allowed to settle a minute and 250ml of 20% NaCl solution is added and epoxide is extracted with ethyl acetate preferably or toluene/dcm and is washed 2x/w n20%NaCl solution. Then the obtained epoxide in solution was refluxed directly in ethyl acetate after drying with epsoms with 700mg of LiI obtained from photography batteries. If ethyl acetate is not avail then hydrolysis with h2so4 is possible by the very familiar procedure to most I'm sure. The final yield was 4.33g piperonylacetone.

More elaboration can be provided on various things and yields if anybody whishes to dream about recreating or tweaking this method for isosafrole and other similar compounds.

[Antibody2]

1) how well does that scale?

2) could you elaborate on the stainless steel plate, size of vessel etc. pls.

3) where is methyl cyanide otc?

thanx
"All those memories lost like rain..."

[Rhodium]

Methyl Cyanide (acetonitrile, CH3CN) is not OTC anywhere I know of.

[foxy2]

I have not seen it in person, however on the web it is listed as a fingernail polish remover.  There are reports of deaths due to drinking ACN fingernail polish remover.

google
Do Your Part To Win The War

[terbium]

solution separated by a stainless steel blade
This part I don't understand. What is the purpose of the "stainless steel blade"?

[boppesz]

The reaction also can be done in DMF or DMSO

[sYnThOmAtIc]

No methyl cyanide is not otc but other dipolar aprotic solvents are, MEK, acetone, THF, ether, DCM, DMSO, DMF, and formamide the latter three can be synthed pretty easily.  Plus others, dunno just look up solvents that lack an OH grouping. 

Pinky tried using MEK alst night as direct replacement after distilation and got 4.35g. As soon as I track down pinky and my calipers I will give the exact dimensions of anodes and cathode. The cathode was just a blade from a stainless butter knife that had been hacked off to use in the experiment. Correction on the 93% it is 89.9% from iso to acetone with methyl cyanide.

But this one yielded 90.4% from the same 4.38g ammont with MEK.

[sYnThOmAtIc]

Terbium: SS balde is the cathode with two graphite anodes on either side of the blade.

The electricity discharging into the solution oxidizes the compound at the anode and the cathode reduces but the epoxide can't be reduced until further workup so there is no need for a partition in the cell as would be if this were a reduction reaction which the product of this goes next.

[uemura]

Bees,
This gives a bit more details. It is extracted from Rhodium site, see

https://www.thevespiary.org/rhodium/Rhodium/chemistry/guest.phenylacetone.txt

for a full description.

Therefore, the object of the present invention is a process for preparing 3,4-dimethoxyphenylacetone, characterised in that:
(a) isoeugenol-methylether, having the formula: 3,4-(MeO)2.C6H3.CH=CH.Me is submitted to an electrolysis in a not-partitioned electrochemical cell, in a medium comprising a dipolar aprotic solvent and an aqueous solution containing an alkali metal bromide or an alkali-earth metal bromide or a quaternary ammonium bromide, in such an amount as to have at least 0.6 mol of Br- ions per water litre, with graphite anodes or anodes constituted by titanium, coated with oxides of precious metals of the VIII group or with mixed oxides thereof with valve metals selected from Ti, Nb, Ta and Zr, and that:

(b) the epoxide isolated from the reaction mixture resulting from (a) step is submitted to an isomerization, in an inert organic solvent and in the presence of catalytic amounts of a lithium salt selected from lithium iodide, bromide and perchlorate, by being heated at temperatures comprised within the range of from 50° C to the solvent refluxing temperature, to produce a methyl ketone III. The electrolysis reaction (a), leading to the formation of the epoxide, can be carried out both batch-wise and continuously, at temperatures comprised within the range of from 0° C to 50° C, preferably of from 10° C to 30° C, with current intensities higher than 100 A/m2 being used, and with the reaction mixture being kept stirred, by a stirring of mechanical type, or obtained by exploiting the turbulence as generated by the gases formed during the electrochemical reaction.

As the dipolar aprotic solvents, e.g., acetonitrile, dimethylformamide, dimethylsulphoxide, sulpholane, N-methylpyrrolidone and dimethylacetamide, preferably acetonitrile and dimethylformamide, can be used.