Synthesis of mescaline using Al/Hg reduction

tetraedr · Mon Apr 18, 2005 11:08 pm

Here I want to present some partly successful synthesis of M.

In 0.5 L glass was amalgamated 6 g of aluminium foil (see more detail about amalgamation in PiHKAL). To this wet foil was added the solution of 4.03 g (16.86 mmol) of 3,4,5-trimethoxyphenylnitrostirene in hot mixture of 10 mL of AcOH (GAA) and 40 mL of IPA. Reaction mixture have to continuous mix by stick within next 10 min. After 1-2 min an exothermic reaction was started, solution becomes colorless and boiled. When this process becomes to run so intensive, it can takes easy by addition some water into glass. The external cooling not a necessary (?). Reaction was complete after approx 1 hour. Almost all foil should be dissolved. The mixture was diluted with 150 mL of cold water, basified with alkaline solution, the product was extracted three times with DCM, organic layers were washed with water, dried with sodium sulfate and solvent was removed under reduced pressure (temperature not higher, than 40 grad). The clear almost colorless residue was dissolved in IPA, acidified carefully with cooling by conc. HCl until pH 5-6, diluted with ether. Then solvents were removed from obtained brown oil, and residue was treated with acetone, filtered off, washed with acetone with obtaining the white crystals of M. Yield – 1.12 g (27%) – hydrochloride.

After some works, I have collected some experimental data about reduction of nitropropenes and nitrostirenes using LAH or Al/Hg conditions for different starting materials. Here I give it in a table.

Entry..Substrate............................................LAH yield......Al/Hg yield..PiHKAL yield
1........2,5-Dimethoxyphenylnitrostirene..........96 (solvent)..93 (bad?).....81
2........2,5-Dimethoxyphenylnitropropene........99 (solvent)..failed...........92
3........4-Fluorophenylnitropropene..................no data........80...............no data
4........3,4-Methylenedioxyphenylnitropropene..74...............83...............56
5........Phenylnitropropene..............................no data........56...............no data
6........3,4,5-Trimethoxyphenylnitrostirene.......69................27...............84

It is interesting to note, that using Al/Hg conditions are better than using LAH only in the case of MDA and 4-FA. Probably, also for amphetamine and 2C-H. The data for 2,5-dimethoxyphenyl derivatives are not correct, because there are oils, and they were not dried completely from the solvents, but next steps for LAH- products for entries 1 and 2 proceeded with satisfied yields, but preparing 2C-B from 2C-H, obtained using Al/Hg method was with yield about 30-40%.

Amount of free bases, obtained using Al/Hg method for entries 5 and 6 was quite good (approx 80-95% yield), but, I think, these bases contain impurities and some solvents. Therefore the yield of white pure (ready-for-use) crystals from these oils was low.

anime · Mon Apr 18, 2005 11:29 pm

Is the 2C-H obtained from the Al/Hg reduction purified or is the crude product subjected to the bromination. What bromination method are you using for this? 93% yield on the reduction seems pretty good.

Concerning the reduction of the 3,4,5 precursor. I know that the nitrostyrene has to be fairly pure for this reaction to occur successfully or with high(er) yields. Curious to whether the nitrostyrene was recrystallized or not.

Sandmeyer · Tue Apr 19, 2005 12:24 am

I'm more curious in the details (catalyst employed, yields obtained) of 3,4,5-trimethoxynitrostyrene synthesis. Could you bee kind to post it?

biobrew · Tue Apr 19, 2005 6:57 am

I am also curious about the 2-CH. Size of RXN?....93% does sound enticing.

IndoleAmine · Dreamreader Deluxe

Thanks, now I've got nothing more to discover and will turn to other reduction methods, since you have tested Al/Hg on virtually all important nitropropenes/styrenes so far, nothing to do for me anymore here. (Hmpf) Evil or Very Mad

No serious, good work!! Very Happy

i_a

IndoleAmine · Dreamreader Deluxe

And you're sure about 2,5-dimethoxynitrostyrene? I don't believe you got better yield with Al/Hg than with LAH used on this substrate, especially since you mention that the amines obtained are not pure sometimes?

for the 3,4,5-triMeO, maybe try using no additional H2O, instead better use alcohol solvent and external cooling to keep things below 40-50°C, and let the reaction run longer. Your rxn conditions for this substrate sound very, well - vigorous.... Wink

tetraedr · Tue Apr 19, 2005 9:39 am

Sorry, only some short answers and additions - have no time in present.

All starting aldehydes were not a home-made - commercial products.
Conditions for Henry reaction (as a rewiev) will be published later.

SWIM did NOT recrystallisid starting nitropropenes (and nitrostirenes) for ALL cases - LAH and Al/Hg reductions.

Scale for 2C-H was about 4-5 g of starting nitrostirene.

Bromination method - just droppind bromine to MeOH solution of starting material, mix at r.t. for 1 h, then work up as usually. Yields for bromination products, have been made from LAH reduction products - about 75%.

jory · Sun Apr 24, 2005 8:48 pm

brain · Linguist Extraordinaire

i tried this, get gray crystals ! with brown spots !!

can't you clen it on tlc ? it is the best way for puryfy this substance?

tetraedr · Mon Apr 25, 2005 12:34 am

you can simply wash the crystals on the filter with dry acetone. Until the white colour. But, probably you will lose some part of substance during this procedure...

brain · Linguist Extraordinaire

than you can freez acetone-then rest of mescaline willl crystalize...?

IndoleAmine · Dreamreader Deluxe

What about the sulfate, which can be recrystallized from H2O very nicely?

tetraedr · Mon Apr 25, 2005 9:14 am

I did not try the sulphate.

And also, I did not try to get the rest of product from filtrate. I just tried to evaporate the filtrates, dissolved it in water, basyfied, exftracted with DCM, evaporated, dissolved in IPA and made the new HCl salt again. No sucessful.

But this product VERY sensitive to heat and to acid-base manipulation. It is converted into brown shit very quickly. Try to cool solutions on every stages!!

IndoleAmine · Dreamreader Deluxe

And avoid having local pH spikes of extreme values when doing a/b extractions - always use dilute solutions of everything.

About "basyfied, exftracted with DCM": DCM is too reactive, better use Et2O instead.

For purifying small amounts, theres always column chromatography if recrystallization doesn't work..

jory · Mon Apr 25, 2005 6:39 pm