01-14-04 06:59
No 482318
I'm curious if the following hypothetical synthesis would work. If so, then it will probably be SWIM's next project after he gets done making mescaline.
(1) Isomerize eugenol with a base to form isoeugenol. (I understand that eugenol doesn't isomerize easily, so it might be easier to do this after the methylation.)
(2) Methylate to form O-methyl isoeugenol.
(3) Run a performic epoxidisation, then add dilute H2SO4 to form 3,4 dimethoxy P2P
(4) Brominate or iodinate to get 2-halo 4,5-dimethoxy P2P
(5) methoxylate with an alkali methoxide or hydoxylate, then methylate to form 2,4,5-trimethoxy P2P.
(6) form the oxime with hydroxylamine, then reduce to yield TMA-2.
I don't know how stable the ketone chain would be under steps 4 and 5. One cannot halogenate methyleugenol directly, since the halogen would also substitute across the double bond, but this synth might sidestep that issue, depending on the stability of the ketone. This avoids the obnoxious sensitivity of asarone, though, and starts from a much cheaper and purer oil (clove or cinnamon leaf).
Thanks for any help/suggestions/reasons why this wouldn't work/flames,
MethyMouse
I've got the kind of toys you've never seen
Manmade and a bit obscene
(Chief Bee)
01-14-04 13:59
No 482354
I don't know how stable the ketone chain would be under steps 4 and 5.
It will not survive intact, but if you make the ethylene glycol ketal of the ketone first it can take the abuse of step 4/5, and then you can deprotect it afterwards.
This general procedure is described as steps F & G in Fig 1 of http://journal.kcsnet.or.kr/publi/bul/bu
You mioght also want to look at this article (also see the pictures in the PDF, as they help a lot): Post 479459 (GC_MS: "Novel syntheses related to asarone", Novel Discourse)
The Hive - Clandestine Chemists Without Borders
(Stranger)
01-14-04 17:10
No 482377
Rhodium, you are really a wonder! That protection mechanism is very simple, and OTC. The acid sensitivity of the protected group will make the isolation of the intermediate phenol slightly more difficult (can't simply add HCl and filter
), but everything else should be really straightforward. Thanks a lot!
Addendum: The p-toluenesulfonic acid catalyst can be prepared easily from toluene and sulfuric acid. See Post 462272 (roger2003: "Alkylbenzenesulfonic Acids", Chemistry Discourse), Post 389646 (Antoncho: "Toluenesulfonic acid - tips and tricks.", Methods Discourse), and Post 261000 (Chromic: "p-toluenesulfonic acid", Chemistry Discourse).
Also, I would prefer that SWIM not have to deal with elemental bromine, but in situ bromine generation requires acidic conditions with a strong oxidizer present. Would something like NaI/I2 selectively halogenate the 2-position as well?
I've got the kind of toys you've never seen
Manmade and a bit obscene
(Hive Addict)
01-18-04 08:45
No 483142
Well kind of.. Since you brought up the tosic acid prep I have to ask a question...
Now - here's a REALLY simple way brought to you by Zaratystra of HyperLab:
"I did it like this: refluxed w/stirring sulfuric and toluene for 15-20 mins, then tenderly decanted the upper toluene layer into a saucer. On cooling, there happened crystallisation of pretty white xtals. The trick works beecause tosic acid (monohydrate) is very well soluble in hot toluene, and very little soluble in cold."
What were the ammounts used in this reaction? I'm assuming the usual 3:1 toluene to acid, but I'm wanting to know how many ml's were used and how many grams of crystals were obtained.
Also, someone ought to really try that vanillin-> asaronaldehyde so that we can know if it is worth trying. I had my hopes all up untill rhodium commented on a possible problem realted to its making, but of course was definately worth knowing!! I'm not complaining, just sad..
(Newbee)
01-20-04 18:31
No 483568
Swim has some vanillin and everything else needed to make run the proposed synthesis of asaronaldehyde, but no nitroethane. He could easily make TMPEA from it, but that may or may not be active, and may or may not be neurotoxic like hydroxydopamine. I notice that Shulgin was not exactly anxious to try it.
I've got the kind of toys you've never seen
Manmade and a bit obscene