Mescaline synth proof read needed, thanks

[L42L]

Fuzzy buzzy friends,
I have a purely theoretical story to tell, it goes like this

Thank you so much for your time,

AFOABee finds its self with a very meager (10g) supply of 3,4,5-benzaldhyde and the possibility of the appropriate amount of LAH. This just might bee a once in a lifetime chance and needless to say the most must bee made of this wonderful situation.

Maximum yields and negligible mechanical loss is the goal, so any words from elder wiser bees are very much appreciated.

After some study at Rhodium and TFSE, some questions remain,

Aldhyde>styrene Best method?

From what it can gather the cyclohexylamine/glacial acetic acid method would be best for 3,4,5 (ala Shulgin) In this case 10g aldhyde, 20-25 ml nitromethane, and 10 ml cyclohexylamine? Any thoughts on side reactions/yield loss concerning the time and temp of reaction? Plan on 100 C for one hour (ala Shulgin)

If cyclohexylamine can not bee had then the straight nitro/anhydrous ammonium acetate reflux will be used. Is .5g catalyst overkill? Reflux for 4-6 hours? Concerned about side reactions mentioned by Shulgin.

Again wish to avoid mechanical loss, Zwtterion (at Rhodium) say’s the hell with a recrystallization of the styrene:

 “No, we didn’t recrystallize from boiling isopropyl alcohol, because, well, why? It’s a clean nitro product, and it’s going to get reduced by a very specific reducing agent later on, so there.”

He was speaking of the 2,5, can I assume the same with the 3,4,5?

LAH Reduction:

OK, let it get this straight, the styrene has a low solubility in et2O? That’s why this coffee drip modified soxhlet thing can be used with out delivering the styrene to fast? If one can be had, great, but she isn’t so lazy that she can’t just drip the styrene (in et2O) slowly through the condenser by hand. Would love to have this thing do the addition all by its self but she doesn’t feel comfortable with it. Any thoughts on this?

Any way, LAH strategy:

In well ventilated area, no smoking, with fire extinguisher handy. A blanket of nitrogen is added to Dry Et2O; chilled on cold oil bath, stirring, and LAH is slowly added. Grams of LAH used=80% of grams styrene used. True?

Styrene is dissolved in et2O and small drop by drop is slowly, slowly added through condenser keeping the reaction nice and calm (screw that mod soxhlet thing, she don’t think she trust it).  Once addition is complete bath is allowed to slowly come to room temp and a nice slow reflux is started. So how long? Can I assume that there is no such thing as too long a reflux? How bout 24 hours? That’s a nice round #. Again, yield is the word.

Work up:

OK, sludge sucks. So ether a work up with potassium sodium tartrate (ala shulgin) or Beagle’s method (“notes on LAH reduction of nitrostyrenes” at Rhodium) will be used.
She thinks she will go with Beagle’s method (proper amount of h20, naoh result in granular consistency of salts). Slowly with ventilation….Any thoughts on the quench are very much appreciated.

She has little confidence in this acid base stuff, please proof read carefully,

After filtration:
Aqueous layer saved and washed with some et2o.
Aqueous layer basified with concentrated naoh to at least pH 9 .
Aqueous layer extracted with DCM
DCM layer saved and evaporated.
Residue dissolved in 99% IPA
Concentrated HCl added until no more crystals form.
Crystals filtered.
 
Did she get that right? (want to avoid the HCl gassing method)
She assumes that concentrated HCl must be used, not the 3?% muritic acid variety, true?

 She knows this synth has little impact on most hive members as old school LAH is such a bitch and 2C-H is more popular, but this does mean a lot to a small bunch of bees who have yet to get their wings. Your time just reading this rambly mess is appreciated; your comments/advice/experience is honey to me.

Well that’s the story, hope to adapt it to a screen play soon, your comments will help insure the scientific accuracy of this exciting piece of fiction.
Thank you.

[Rhodium]

Again wish to avoid mechanical loss, Zwtterion (at Rhodium) say’s the hell with a recrystallization of the styrene:

 “No, we didn’t recrystallize from boiling isopropyl alcohol, because, well, why? It’s a clean nitro product, and it’s going to get reduced by a very specific reducing agent later on, so there.”

He was speaking of the 2,5, can I assume the same with the 3,4,5?

No, it depends on too many factors. Either recrystallize or confirm purity by TLC or melting point test.

OK, let it get this straight, the styrene has a low solubility in et2O? That’s why this coffee drip modified soxhlet thing can be used with out delivering the styrene to fast?

Yes & Yes.

If one can be had, great, but she isn’t so lazy that she can’t just drip the styrene (in et2O) slowly through the condenser by hand. Would love to have this thing do the addition all by its self but she doesn’t feel comfortable with it. Any thoughts on this?

Due to the low solubility in ether, you need to dissolve it in an unrealistically large volume of solvent before the addition. Adding the nitrostyrene dry may lead to inreased byproduct formation.

I suggest that you either add the nitrostyrene as a THF solution or that you use a pressure-equalized addition funnel placed inbetween the reaction flask and the condenser instead of that "modified soxhlet extractor" as both setups will in essence function identically. A soxhlet filter or equivalent is still needed so that undissolved nitrostyrene isn't washed into the reaction flask.

Residue dissolved in 99% IPA
Concentrated HCl added until no more crystals form.
Crystals filtered.
 
Did she get that right? (want to avoid the HCl gassing method)
She assumes that concentrated HCl must be used, not the 3?% muritic acid variety, true?

You may lose product this way regardless if you use 30 or 37% HCl, depending on how soluble mescaline hydrochloride is in the resulting wet IPA solution.

[L42L]

You’re the best Rhodium, no really.

#1. Will recrystallize then.

#2. Then THF will be used as the styrene addition solvent (if she cant get some sort of coffee drip style delivery system) seems like an unpacked fractionating column filled with a matrix of glass wool and styrene could be used if only it was very sure not to plug up (that would suck or should I say blow).

#3. Well at this scale I guess gassing isn’t that big of deal.

Ok, getting warmer. All I need now is some bee with real 3,4,5 experience to tell me that a 24 hr reflux is/isn’t overkill. Should she just Shulgin it and go 48 (if I remember correctly) hours?

Ya all rock,
Thanks Rhodium

[terbium]

Mescaline is often crystallized from water as the sulfate because this salt is very soluble in hot water and only sparing soluble in cold water.

From the Merck Index:

  5965.    Mescaline. 
  3,4,5-Trimethoxybenzeneethanamine; 3,4,5-trimethoxyphenethylamine; mezcaline.  C11H17NO3; mol wt 211.26.  C 62.54%, H 8.11%, N 6.63%, O 22.72%.    Psychotomimetic alkaloid isolated from peyote (mescal buttons), the flowering heads of Lophophora williamsii (Lemaire) Coult., Cactaceae.  Isoln:  A. Heffter, Ber. 29, 221 (1896).  Structure and synthesis:  E. Spth, Monatsh. 40, 129 (1919); K. H. Slotta, H. Heller, Ber. 63, 3029 (1930); E. Spth, F. Becke, Monatsh. 66, 327 (1935); M. U. Tsao, J. Am. Chem. Soc. 73, 5495 (1951); K. Banholzer et al., Helv. Chim. Acta 35, 1577 (1952).  Novel synthesis:  M. N. Aboul-Enein, A. I. Eid, Acta Pharm. Suec. 16, 267 (1979).  MS determn:  S. P. Jindal, T. Lutz, Eur. J. Mass Spectrom. Biochem. Med. Environ. Res. 2, 117 (1982). 
  Pharmacokinetics in rabbits:  C. Van Peteghem et al., Eur. J. Drug Metab. Pharmacokinet. 7, 1 (1982).  Mode of action study:  M. E. Trulson et al., Eur. J. Pharmacol. 96, 151 (1983).  Use in evaluating serotonin S2 antagonists:  C. J. E. Niemegeers et al., Drug Dev. Res. 3, 123 (1983).  Evaluation of use with chlorpromazine, q.v., in various psychoses:  H. C. B. Denber, S. Merlis:  J. Nerv. Ment. Dis. 122, 463 (1955).  Toxicity data:  L. B. Speck, J. Pharmacol. Exp. Ther. 119, 78 (1957); H. F. Hardman et al., Toxicol. Appl. Pharmacol. 25, 299 (1973).  Reviews:  A. R. Patel, Progress in Drug Research vol. 11, E. Jucker, Ed. (Birkhauser Verlag, Basel, 1968) pp 11-47; G. J. Kapadia, M. B. E. Fayez, J. Pharm. Sci. 59, 1699-1727 (1970).
          Crystals, mp 35-36 deg.  bp12 180 deg.  Moderately sol in water; sol in alcohol, chloroform, benzene.  Practically insol in ether, petr ether.  Takes up CO2 from the air and forms a crystalline carbonate.  LD50 i.p. in rats:  370 mg/kg (Speck).
          Caution:  This is a controlled substance (hallucinogen) listed in the U.S. Code of Federal Regulations, Title 21 Part 1308.11 (1995).

          Hydrochloride, C11H17NO3.HCl, needles, mp 181 deg.  Sol in water, alcohol.  LD50 in mice, rats, guinea pigs (mg/kg):  212, 132, 328 i.p. (Hardman).

          Sulfate dihydrate, (C11H17NO3)2.H2SO4.2H2O, prisms, mp 183-186 deg.  Sol in hot water, methanol; sparingly sol in cold water, ethanol.

          Acid sulfate, C11H17NO3.H2SO4, crystals, mp 158 deg.

          N-Benzoylmescaline, needles from aq alc, mp 121 deg.  Very sol in alcohol, ether.

          N-Methylmescaline, occurs naturally, bp 130-140 deg.

          N-Acetylmescaline, occurs naturally, mp 94 deg.

[L42L]

The prop dept has further concerns,

Any bee have any suggestions as to an appropriate amount of et2o and size flask to use assuming a 10g nitro/LAH using the mod soxhlet method? Would rather error on the side of safety. Any bee have an idea just what is the solubility of the 3,4,5-nitro in et2o?

Thanks all.

[hest]

The condensation of the aldehyde with nitromethane is the big problem. The reduction will work in almost kvant. yeald.
read

Post 422844

(Bandil: "Verification of Bariums research", Methods Discourse)(the whole post) Barium makes the ethene in 92%. I'm sure that an 0,5L ether in an 2L flask will work.
Dont use a soxhlet !!!! use an modified soxlet as Shulgin does. Teknical it just an pressure-equalized addition funnel with an soxhlethfilter inside. Just as the cheef sayes
You don't want to add alot of styrene at once (as you will with an soxhlet) I'v once sean a 30g reduction explode with STP becourse the chemist did'nt know the diff. betwean an modified soxhlet and an ordinarye soxhlet.

[L42L]

Thanks Hest!

I love the hive, where one bee’s common sense and reckless ignorance can be found to be the exact opposite in another bee.

Her “common sense” (ha)
Yes she know the difference between mod and normal soxhlet, thank you though, if she didn’t…..yea, this is a no stunt crew movie.

Her reckless ignorance
If she took Shulgin as her guide (his ratio of et2o/lah) I think I would run a 10g reaction (mod soxhlet style) in a L worth of et20. Just seems like over kill, yea 500 mL “seems” appropriate to me, but would love to hear thoughts from the hive. Thanks all

Any way…

Thanks for the link, can’t remember seeing that one from her original searching.
Unfortunately it just confirms what “conclusions” she already has come to:

The highest yielding method “known” (aldehyde too syrene) for the 3,4,5, (not any other) is the cyclohexamine/glacial acetic acid reflux. IF ANY BEE HAS ANY COMENT ABOUT THIS STATEMENT, BUZZ LOUDLY! Thank you.
 
BTW: Your post No 444231 kinda has her drooling (microwave styration) got some refs?
(Not that she would have the oveez to try with limited 10g aldehyde)

Again bees, any comments welcome! (500 mL ok? any “better” ideas than cyclohexamine/GAA?)
 
A thousand thanks

[GC_MS]

This is how you can make mescaline the easy way (at least in my opinion):

1. Make the nitrostyrene from 3,4,5-trimethoxybenzaldehyde and MeNO2 in GAA with cyclohexylamine a la Shulgin (

http://www.erowid.org/library/books_online/pihkal/pihkal096.shtml

). This method really is very easy and yields are always near what Shulgin writes, even if you are a n00b.

2. Reduction of the nitrostyrene via Zn/HCl, as described in

Post 245040

(Rhodium: "O Leminger's Phenethylamines - posted by Karel", Novel Discourse). Yield of mescaline should be around 50%, even for n00bs (see

Post 400235

(GC_MS: "yield", Novel Discourse)).

3. Crystallization: dissolve the amine freebase in ethanol and neutralize with 50% H2SO4 (as in the Leminger document). Put the crystal mush in the fridge and filter it (vacuum) after a few hours. Recrystallize the mush from hot water and allow to cool it down slowly to get impressive translucent needles.

Bioassaying: If you have never tried mescaline, start with 200 mg (of the sulfate) for the first experiment, and 300 mg for the second. After that, you can take whatever you want   . Also, ingest the weighed amount in at least two times (with ca 30 min inbetween) to limit gastric protest.

Enjoy, you'll find it a most wonderful compound   .

[Grimble_Gromble]

What is the difference between a "modified soxhlet" and an ordinary soxhlet"?. Would be the size of the extraction chamber?
I didn´t understand very well: Can I use a pressure-equalized funnel with a thimble inside, put a condenser on the top of the funnel and I open the tap a little bit?
Why Can´t I use a commom funnel?

Sorry the lots of "whys"

Regards,

[hest]

Well I have a good day so I anser.
An soxhlet is a chamber witch will bee filled with solvent and emtyet at once dovn the reaction, jus like a bucket you fill with wather and then turn upside down. result is a lot of disolved nitrostyrene added to your LAH and somtimes a wiolent reacton. A modified is just the material hanging in the air where the condensed solvent drip dovn and then drip into the reacton, rsult is small drops of disolved material added to the reacton and no wiolent reacton.

[L42L]

Thanks GC-MS,
but yeilds are the key (only 10g aldhyde)

OK so for whats it worth, the prop department has decided that if we use a 2L RBF and 750mL et2O for the reduction (assume 10g) every thing will be OK and we will have no need for any stunt doubles. IF ANY BEE HAS ANY ISSUE WITH THIS DECISION PLEASE BUZZ NOW!

thanks all!