vanillin->mescaline

[improv_chem]

SWIM's friend just started working at a health food store that is ordering in some absolutely pure vanilla powder so SWIM is looking for the best otc way to make some goodies.  I've read a bunch of stuff about this from rhodium's and elsewhere but would like to ask if anyone here has some practical experience with these kind of procedures.  A few questions;
1.  If you take the vanillin and react it with nitromethane and ammonium acetate, then reduce with Hcl/Zn or Al/Hg to get an amine would the OH on the ring cause any problems or solubility differences from common ways to isolate amphetamines.
2.  Should you then react with dimethyl sulphate or should you first brominate the 3-position. 
So the sequence of events might look like;
1.  react vanillin with nitromethane and amacetate.
2.  reduce the nitro to a PEA with Zn/HCl or Al/Hg.
3.  react the PEA with dimethyl sulphate to get your 4,5-dimethoxyPEA.
4.  Brominate the 3-positon with bromine and GAA.
5.  reflux in NaOH to get the 3-hydroxy-4,5-methoxyPEA.
6.  React with dimethyl sulphate to get your 3,4,5-trimethoxyphenethylamine.
Is SWIM on the right track here or is this messed up? 
This seems to be a totally otc route to mescaline if it would work.
Any suggestions would be very much appriciated.
-improv
Let's play with nature a little, I'm sure we can make her a little higher....

[otto]

Hi SWIM,

in answer to your second question, you have to introduce the bromine bevor you methylate. 3,4-DMPEA from your third step would be brominated to the 6-bromo-compound, not to the desired 5-isomer.
on rhodiums page are some good procedures dealing with the vanillin-to-mescalin-route.

otto

[catastrophe]

   

Any suggestions would be very much appriciated.

UT'FUCKING'SE!!

[Chromic]

If I was to do this, I'd have to try 3-bromo-4,5-methoxyphenylethylamine as well. ie methylate/brominate/nitro-aldol/reduce.  

Not having looked at the synthesis on rhodium, to make mesc, it looks obvious to brominate, hydroxylate w/koh, methylate w/dms, nitro-aldol, reduction of nitrostyrene.

Btw, I imagine yields will look plenty bad.

[megamole]

https://www.thevespiary.org/rhodium/Rhodium/chemistry/345-tmb.html

Its the best-looking route to 3,4,5-TMB I've seen.

[halfapint]

Yeah, it's nice. Chromic's way serves for those without metallic Na on hand to make sodium methoxide. Rhodium, did anybody ever figure out if you could use magnesium methoxide to methylate? Just brewed up a fresh batch, so I guess I'm the one to ask. On the dimethylcarbonate thread, I figured allyl methyl carbonate must bee about the lightest in that series that you could use to methylate by simple boiling, without a pressure vessel. DMS or MeI, alas, are still about the easiest methylating agents to come up with.

If I have any spare Mg(OMe)2 left over after a bromopropionic nitroethane run, I'll let you know if it methylates vanillin.
turning science fact into <<science fiction>>

[Rhodium]

Chromic: The yields won't be too bad using that method.

Halfapint: I haven't heard of anyone using the Mg(OMe)2 alkoxide yet, but neither I or Osmium cannot find any reason why it shouldn't work. Oh, you are working on that wonderful nitroethane synth, please let us know how it goes.

[moo]

Excuse me, but tt is ridiculous that the magnesium alkoxide methoxylation is yet to be tested, although the chemicals needed are so common. I am quite positive it wouldn't be a major pain in the ass for those in the position to do so. Well. Maybe some day.
^{understanding is everything}

[improv_chem]

SWIM is getting pretty excited now upon making some Na metal by decomposing NaN3.  Seems to be a pretty violent decomposition though, might be rough if you scale it up beyond a little bit in a test tube with a ballon over the top.  Oh, the Ideas are pouring into my mind at this very moment... Many small beads of sodium.... mabe that NaOMe is practical for SWIM after all!  I'll keep you posted if SWIM discovers a nice sodium preparation, it might be just around the corner....
->If I was to do this, I'd have to try 3-bromo-4,5-methoxyphenylethylamine as well.
Do you mean eat the stuff?  Would this be active at reasonable levels?  If it is, it would be a few steps shorter than making mescaline.
-improv
Let's play with nature a little, I'm sure we can make her a little higher....

[foxy2]

I would bee pretty excited too, knowing I only have a short while to live and all.  I wouldn't try whatever it is you are trying.   NaN3-> Na + 1.5 N2

Do Your Part To Win The War

[Rhodium]

I believe 3-bromo-4,5-methoxyphenylethylamine would be reasonably active, and the amphetamine analog would definitely be.

[otto]

hi improv_chem,

i know, what you are looking for is sodium methoxide, but concerning sodium ethoxide, there is no need for sodium metal. the reaction NaOH + EtOH <--> NaOEt + H2O is an equilibrium that can be shifted by removing the water out of the reaction mixture. so, a solution of NaOH in Ethanole will give, when the water is destilled off as azeotropic mixture, a solution of sodium ethoxide in ethanol. a compound that forms an adequate azeotrop is needed to add (e.g. benzene, CCl4, C2HCl3 and the like).
unfortunately this seems impossible for the analogous precedure with methanole since there is no adequate azeotropic mixture known.

otto

[foxy2]

The azeotrope database says that ethyl ether forms an azeotrope with water(98.8% EE, bad ratio) but it dosn't say anything about methanol.  EE probably does have an azeotrope with methanol, however if it dosn't then this would work for dehydration.
Do Your Part To Win The War

[Osmium]

Well, once you have the NaOEt you can dissolve that in a big excess of MeOH. Due to the equilibrium you will end up with a solution containing both NaOEt and NaOMe, their ratios depending on their (only slightly differing) pKa values and the respective concentrations.
I'm pretty sure that concentrating the solution with a rotovap, adding more MeOH and repeating this a few times you will finally end up with largely NaOMe (and a lot of NaOH and Na2CO3 due to water traces in the solvents and CO2 from the air   ).
Azeotropic compositions are influenced by vacuum, so maybe a mixture of toluene/MeOH or benzene/MeOH or whatever could be used to boost the methanolate content when doing it under vacuum? Dunno, doesn't sound too promising, but I still wouldn't rule it out completely.

Guess that leaves only one other possibility:
Mg(OMe)2 + 2 NaOH ---(MeOH)---> Mg(OH)2 + 2 NaOMe

Since the Mg hydroxide will be insoluble in methanol this reaction should produce a solution of NaOMe.