Mescaline synthesis

[Chimimanie]

This one was cited in tfse but if you wanna download it, here it is:

Mescaline synthesis via tricarbonyl (h6-1,2,3-trimethoxybenzene)chromium complex

Inorganica Chimica Acta 300–302 (2000) 693–697

(https://www.thevespiary.org/rhodium/Rhodium/pdf/mescaline-barbier.pdf)

Abstract:
Treatment of tricarbonyl(h6-1,2,3-trimethoxybenzene)chromium complex 1 with acetonitrile carbanion in THF and then with iodine followed by reduction of the nitrile function gives mescaline. Deprotonation of complex 1 at the C5 carbon with LiTMP followed by chlorination, bromation or iodation gives 5-chloro, 5-bromo or 5-iodo complexes, useful synthons in organic synthesis for the preparation of 1,2,3-trimethoxy-5-substituted derivatives, precursors of natural products.


It contains the following interesting refs:

(a) L. Reti, in: R.H.F. Manske, H.L. Holmes (Eds.), The Alkaloids Tome III, 1953, p. 313.
(b) E. Spath, Monatsh. Chem. 40 (1919) 129.
(c) K.H. Slotta, H. Heller, Chem. Ber. 63 (1930) 3029.
(d) M.U. Tsao, J. Am. Chem. Soc. 73 (1951) 5495.
(e) K Banholzer, T.W. Campbell, H. Schmid, Helv. Chim. Acta 35 (1952) 1577.
(f) D. Amos Aust. J. Chem. 45 (1964) 58.
(g) M.N.Aboul-Enein, A.I. Eid Acta Pharm. Suec 16 (1979) 267.
(h) F.Benington, R.D. Morin, J. Am. Chem. Soc. 73 (1951) 1353.
____ ___ __ _

Here is another synthesis of Mescaline:

An a-aminomethyl carbanion equivalent via a novel Barbier reaction: (1H-naphtho[1,8-de]-1,2,3-triazin-2-yl)methyl anion

Tetrahedron Letters 41 (2000) 4685-4688

(https://www.thevespiary.org/rhodium/Rhodium/pdf/mescaline.carbonyl-chromium.pdf)

Abstract:
A novel sonication-promoted Barbier reaction putatively generated the titled species from the corresponding naphthotriazinylmethyl chloride and magnesium in THF: its formal addition to a variety of carbonyl compounds in situ occurred in excellent yields. Subsequent catalytic hydrogenolysis of the triazine moiety demasked the amine, thus defining a route to various phenylethylamines (including the alkaloid `mescaline'), or ethanolamines (in two cases), in excellent overall yields.

[Rhodium]

Reading the Barbier article a little closer, it seems like 3,4,5-Trimethoxybenzaldehyde 6d (errorneously referred to as the 2,3,4-isomer in Scheme 1) is actually only converted into 3,4,5-Trimethoxyphenyl-2-(naphtalenotriazino)ethanol 7d by this Barbier reaction, it is only later reduced to Mescaline 8d in by catalytic hydrogenation of 0.3 mmol 7d in 3mL EtOH (10% Pd/C, 1 atm, RT, 24h, 82% yield) followed by column chromatography.



Besides being a very ridiculous nano-scale reaction, doesn't the successful reduction of 7d to 8d that the same reaction conditions would be applicable for the reduction of (pseudo)ephedrine to methamphetamine? And if not, why not?



On another note; For the preparation of Mescaline from LiCH₂CN, 1,2,3-Trimethoxybenzene Chromium Tricarbonyl
is needed, and the preparation of that can be found in either of the journals below:


J. Chem. Soc. Chem. Comm. 1108 (1986)

Inorg. Chem. Acta. 259, 265 (1997)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/mescaline.carbonyl-precursor-1.pdf)

J. Organomet. Chem. 290, 153 (1985)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/mescaline.carbonyl-precursor-2.pdf)

[Aurelius]

Where are you planning on obtaining that N-methyl grouping?  From the looks of the example, the Nitrogen cannot be substituted.  (the longer aliphatic chain poses no problems though)

[supernate]

i remember a while back there was a great reference on www.rhodium.ws/chemistry.....    that gave a whole slurry of neat-o chems that could be distilled from common plant sources. the last time i tried to access that link it didnt work for me but TO THE POINT:     what plant could one concievably distill 3,4,5-trimethoxybenzaldehyde from? or will this have to be synthesized from a more simple precursor?

[Rhodium]

I wasn't suggesting that the Barbier reaction would be used in the methamphetamine synthesis, only that if the Pd/C reduction of the benzylic alcohol worked on the strange-looking mescaline precursor worked, why wouldn't it work with ephedrine? Or is the neighbouring triazine group somehow activating the benzylic alcohol towards reduction?

[supernate]

the triazo species is a very short jump away from a fully conjugated system, which would be very stable, and which would involve the loss of an H2O. this energy drop would be quite favorable in driving toward a R-=-R' intermediate which would then be easily hydrogenated over Pd/C.

With ephedrine, however, there does not exist a possibility for a conjugation of double bonds such that we see in the mescaline synthesis and thus there exists no driving force toward the formation of a hydrogenatable R-=-R' intermediate, thus a more agressive reduction is required. i dont think that one could put that leaving group on to form the triazo conjugated form without sacrificing a n-methyl...

[praeseodymium]

you could... find a nice mature San Pedro cactus- Trichocereus Pachanoi- and extract your desired product from it directly. Unlike peyote this plant grows fairly quickly and has reasonable yields.  A guru on a mountain has used a crude aqueous extraction via boiling the sliced cactus flesh in a large excess of water for several (4-6) hours over a fire in a stainless pot. makes for quite a ritual, similar to the way natives of north america have prepared it for ages. A piece of cactus 400-600mm in length and average width for this species (about 75mm) is sufficient for a pretty hefty trip- there are some related alkaloids also extracted this way, but most of it is mescaline. After boiling the liquid soup is decanted and boiled down to a concentrate, which is swallowed. I can personally attest to the extreme bitterness of this concoction- it is indeed quite possibly worse than the worst thing you can imagine. It can also make you instinctively retch, which makes for quite a mental challenge. But the guru did it again many times when he was young, the taste being considered some amusing biological deterernt for weaker souls. he he.

A much improved technique exploits the high concentration of the alkaloids near the surface of the cactus' skin.
1. Take a good, sharp knife, and with the piece of cactus held standing upright on a solid board, run the point from top to bottom along the 6 or so "valleys" that run along the cactus, cutting in about 25-30mm from the skin, and at such an such that the cut is parallel to the other side of the ridge behind which you are cutting. Then doing the same on the other side of the ridge (the next "valley" over) but with the angle the other way, so you cut a diamond-sectioned slice from the length of the cactus.
Work round the whole cactus and cut all the ridges off this way. You can do a separate extraction with the centre, white-fleshed piece, but the concentration is quite low and the volume of material large.

Depending on how much you like your blender, you can also cut the spines off. There was an (AFAIK) incorrect myth that these spines contain strychnine- other species may have this property, but not T. Pachanoi (this species is fairly popular and grows in most warmer climates).
Cut up the diamond-section slices into shorter peices and blend them up to a green puree. Adding a small amount of water to take some stress of the blender is a good idea, as is adding small amounts- this is fairly solid stuff.

Once it's all fine and mushy you can extract the alkaloid with ethanol or warm water, using some muslin or other fine cloth to crudely strain the material, using about 2 or 3 washes of H₂O. Then re-filter the collected washings with usual filtering technique. It isn't that practical to filter it all in one run.

Then the volume of solvent can be reduced. Ethanol will probably wash some wax from the skin so you may need to defat before proceeeding with an A/B, using a small amount of toluene, hexane, xylene or similar. The mescaline is in a sulfate form so I'd use water.
You can simply evaporate most of the water at this point and drink this- it is considerably less vile than that produced by extended boiling.

But far more tasteful...

After the A/B (aq. NaOH, pH 10-11, ether or the above solvents), mescaline sulfate crystallizes fairly easily so this is probably the ideal salt to aim for.

Mescaline is way cool but treat it with respect. Too much of this can be *real* hard on you.

[supernate]

is that it costs a bundle (relatively) for the cactus flesh where i live. it is possible to order the flesh online, but i was hoping for a cost-effective route to a whole bundle of it (mescaline). it sounds as though using 3,4,5-trimethoxybenzaldehyde as a precursor will be most practical for that. i am growing 7 san pedros to graft Lophophora Williamsii to (they just grow so inconcievably slowly on their own), but thats more of a project than a renewable drug source.

that mescaline sulfate salt is a good piece of info though, ill be using that someday! but if youre doing an a/b anyway, why selectively use certain fractions of the cactii in different batches?
and if youre consuming the crystaline product anyhow, why not vaporize it? (thermal decomp. point?) or stick it in a gel cap?

for obtaining a good few hits, the cactus is The Way, but for retail.....     anyhow, im just dreaming that way right now. my MDMA dream needs realization first!

[Bwiti]

"Then the volume of solvent can be reduced. Ethanol will probably wash some wax from the skin so you may need to defat before proceeeding with an A/B, using a small amount of toluene, hexane, xylene or similar. The mescaline is in a sulfate form so I'd use water."

  Mescaline sulfate? How did you arrive at that? Did you leave out the part where you freebased the mescaline, dissolved it in a non-polar solvent, treated it with H2SO4 and filtered out the sulfate crystals??

[praeseodymium]

I have been under the apparantly incorrent impression for a long time, after reading it, that the form present in T. Pachanoi was in fact the sulfate salt.
However, your query prompted me to verify this and I cannot find anything that would confirm my false impression.
Thankyou for completing and correcting my substandard post.

Since I first arrived, I have made an effort to raise the standard of my posts, and (excepting the Couch) adhere strictly to the facts from experimental literature or other verifiable sources. That is in fact largely why I came here in the first place- I want to enjoy my passion for chemistry without that passion detrimentally clouding my perception.
Being pulled up on details like this is actually a breath of fresh air, even if it is a bit of a slap in the face  

[Rhodium]

No alkaloids are present in plants in a specific salt form, but rather as a salt mixture with several different naturally occuring acids. I think Lilienthal has extrapolated on this topic in the Tryptamine forum.

[Rhodium]

Über die Anhalonium-Alkaloide I. Anhalin und Mezcalin
Ernst Späth

Monatshefte für Chemie 40, 129-154 (1919)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/mescaline.spath.pdf)