OK, so SWIM is about to get back to his lab, and he's been been strongly considering making some mescaline with all the vanillin and nitromethane he has. I haven't done all the calculations, but here's the basic game plan, together with a few questions:
(1) Take vanillin and brominate via in situ bromine generation (H2O2/GAA/H2SO4/NaBr), a la uemura (
Post 297806
(uemura: "How to prepare hydroxyvanillin", Methods Discourse)). The sodium bromide should be able to replace the potassium bromide without any problem (I think).
(2) Place magnesium turnings into methanol with a crystal of iodine; and reflux until all the magnesium has reacted. This should create at best an 8% solution. Then much of the methanol is distilled off, so as to create the equivalent of a 5M solution (in terms of the methoxide ions). Some of the Mg(OMe)2 will crystalize out of solution, but hopefully will disolve back in as the reaction progresses and heat is added. The workup will then be as on
https://www.thevespiary.org/rhodium/Rhodium/chemistry/mmda.mescaline.html
to make syringaldehyde; just replacing the sodium methoxide solution with a magnesium methoxide solution.
(3) The syringaldehyde is then methylated either via DMS or methyl iodide. SWIM is leaning towards methyl iodide, since it is much less toxic and also easier to make. The workup in Vogel with RP/I/MeOH should be fine, though SWIM's also considering generating HI in an iodine/turpentine/methanol solution, and then distilling off the MeI. Methanol and turpentine seem to be miscible, so this should work fine. Trimethyl phosphate would be optimal, but SWIM can't seem to find any phosphorus pentoxide needed to make it.
(4) The 3,4,5 trimethoxy benzaldehyde is then condensed with nitromethane in GAA with an ammonium acetate catalyst in an ultrasonic cleaner, as in
https://www.thevespiary.org/rhodium/Rhodium/chemistry/nitrostyrene.ultrasound.html
(5) Reduce with Urushibara nickel as in
https://www.thevespiary.org/rhodium/Rhodium/chemistry/amph.urushibara.html
Questions:
(1) Comments on step 2 would be much appreciated. Is MgBr2 soluble in methanol/EtOAc?
(2) Is P2O5 available at all? SWIM hasn't been able to find a chemical company which sells to individuals who sells it, nor has he been able to find any OTC sources. Should he bother to keep looking?
(3) Is there any problem with using Urushibara nickel to reduce nitrostyrenes? I've only seen it used with nitropropenes, though I don't know of a reason why it wouldn't work.
Thanks in advance,
MethyMouse