2-Methoxy-4,5-Methylenedioxybenzaldehyde

[catastrophe]

Any reasons this shouldn't work?:

Piperonal is brominated with Br2 in acetic acid (maybe MeOH instead), giving 2-bromo-4,5-methylenedioxybenzaldehyde. The bromo compound is then refluxed with NaOMe/CuBr giving the desired aldehyde.


The methylenedioxy bridge should be fine, right? Shulgin uses alkoxides for his beta-alkoxy additions with sodium methoxide/ethoxide. Think he beta-methoxylates 3,4-methylenedioxyphenethylamine, because he didn't synthesize any amphetamines.

The aldehyde group should also be fine right?


Exhaustive Ranting...
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Of course the aldehyde is for MMDA-2, but if this works, EMDA-2 would also be very easy to synth (shulgin states intense eyes-closed visuals at 185mg).

Any thoughts on how the 4-carbon amino compound(s), alpha-ethyls, would taste? Considering that MMDA-2 is relatively high in activity (compared to MDA) and more potent than its 3,4,5 sister, MMDA, it would seem to be a logical choice. SWIM has heard that extending the chain to a 4-Carbon eliminates ALL psychedelic properties the shorter chain compounds might have had, so it wouldn't facilitate a hallucinogenic state. The N-alkyl compounds would probably be pretty weak. Anyways, one might name these 2-methoxy-J, and 2-methoxy-(M)ethyl-J. Could be interesting.

How about the beta-alkoxylated compound? A beta -OCH3 would probably give an active compound, but maybe not pleasant(toxic?). Or how about a methyl group at the alpha position to give the amphetamine derivatives. How would synthesis go for that? Condense with nitroethane, then sodium alkoxide?? Would beta attack occur if the alpha position was occupied? Shulgin didn't synthesize one of these, so it's probably not that simple.
Of course he does mention beta additions with alkylthiols. If one had a sodium mercaptide, i.e. methylthiolate, it might work. Have any ever been synthesized?? They might be incredibily potent compounds, especially if the right nitrostyrene was chosen. How about a beta halogen addition? Would bromine attack the nitrostyrene at the beta position? ... This might deserve a thread of its own, as SWIM thinks beta-substitution is all that's left to do with these compounds.

So many choices, so little information as to pharmacology. It's a pity.

Any ideas for the aldehyde synth are welcome.

[hest]

a 'mild' reduction will give you the ephedrine annalog (search). From the alcohol you'r almost home

[Rhodium]

Your aldehyde synthesis sounds just right. For details, just pretend your piperonal is the veratraldehyde of this synth:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/tma2.vanillin.html

And for the methoxylation, just pretend 6-bromopiperonal is the 5-bromovanillin of this synthesis:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/mmda.mescaline.html

Edit: I take that back, see

Post 465752 (missing)

(Rhodium: "6-Bromo- to 6-Methoxy-piperonylic acid", Novel Discourse)

[Nemo_Tenetur]

since piperonal is heavily watched. Sesamol and dimethylsulphate (or KOH/CH3I) gives the methoxymethylenedioxybenzene as intermediate. You can now brominate or formylate or acylate (the latter gives you directly the desired 3-carbon-sidechain). If you choose the latter, brominate the methoxymethylenedioxypropiophenone and react with the desired amine. This product should be active (the methoxymethylenedioxycathinone), but you can reduce it to the ephedrine analog, or finally to the MMDA-2.

Yes, this pathway looks a little bit complicated, but I've completed it until the bromoketone. Less suspicious precursors and unscheduled products are the great advantages of this way, IMHO.

[moo]

I presume the bromoketone works as tear-gas too.

[3base]

Post 319795 (missing)

(3base: "MMDA-2: 6-bromopiperonal from piperonal", Novel Discourse)

if you have Br2 but no piperonal at hands then you can make
it from pepper:

Post 317862

(3base: "MMDA-2 precursor from pepper", Novel Discourse)

or you can make MMDA-2 from sarisan, like MDA from safrole.

sarisan (1-allyl-2-MeO-4,5-MD benzene) can be extracted from plants:

Post 324777

(3base: "ashanti pepper oil: myristicin, sarisan", Novel Discourse)

Post 324027

(3base: "MMDA-2: sarisan in beilschmiedia miersii leaf oil", Chemicals & Equipment)

3base  

[Nemo_Tenetur]

From my experience, poly-substituted bromoketones have only few lacrymatory effects. The worst is alpha-bromopropiophenone, somewhat less are para-methoxy-alpha-bromopropiophenone and para-methyl-alphabromopropiophenone. the para-methoxy is a very fluffy solid and tends to fly with the slightest wind, forming a cloud, therefore aggressive to mucous membranes. The para-methyl forms beatiful crystals, heavy, but tends to sublimize enough to be an irritant. The methoxymethylenedioxy, however, is easy to handle, same like 2,5-dimethoxy.

[catastrophe]

Those are excellent posts 3-base! Absolutely enlightening material, great job!

[catastrophe]

Does anybody know if beta attack will occur if the alpha position on the chain is already occupied?
Also, will halogens attack nitrostyrenes readily?

Thanks.

[Rhodium]

Yes, nitrostyrenes are easily attacked by halogens. I don't know if any usable product can be obtained from the reaction though, or if it all turns into a steaming mudpile.

[Throb]

Just an idea.  The mechanism of the bromination (not showed here) is a radicalar reaction.  You could use Br2 with Fe or AlCl3 instead of CH3CO2H.  Please correct me if I am wrong.

Throb