Author Topic: Contest: anise oil as MDMA precursor  (Read 11285 times)

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  • Guest
Contest: anise oil as MDMA precursor
« on: July 03, 2003, 04:15:00 AM »
This is a contest. The winner will be given sexual compensation by a virtual Thai striptease dancer.

I guess a million bees have had a dream to use anethole (anise oil) as MDMA precursor. However, you don't need much chemistry knowledge to see that this is not an obvious synthesis. I have had the plan to perform the necessary syntheses, but I realize that I don't have enough time nor the necessary interest to end the project fruitfully. Hence this contest.
Using TFSE, I haven't seen anybody going into detail on how anethole can be used as MDMA precursor. What you will read now is semi-theoretical, from this point of view that I haven't performed the syntheses myself; but the necessary steps are all described in the literature, and that is what I am going to point at right now. Anybee who does have the time and interest to analyze the possibilities, please do so. You might be able to find improvements or combine 2 or more steps into 1-pot reactions.

Abstract: anethole is the main constituent of anise oil and can be oxidized to 4-methoxybenzaldehyde (aka anisaldehyde). This compound can be demethylated with a strong Lewis acid to obtain 4-hydroxybenzaldehyde. Mono-bromination of this benzaldehyde will yield 3-bromo-4-hydroxybenzaldehyde. The Br can be substituted for hydroxy, giving 3,4-dihydroxybenzaldehyde. Methylenation of this product yield piperonal. Piperonal can be a MDMA precursor in many ways.

Oxidation of anethole to anisaldehyde: There are several ways to accomplish this oxidation: sodium bichromate and potassium permanganate are the best known. I assume the experienced chemist has the necessary knowledge to perform this reaction. Some examples are available for isosafrole and asarone on Rh's website.

Ether cleavage of anisaldehyde: There are several methods to cleave the methoxy bond. The synthesis of 4-hydroxybenzaldehyde from anisaldehyde is described in the following articles:
- Ber Deutsch chem Ges 74 (1941) 1219 (with pyridine.HCl, 200-220°C)
- Ber Deutsch chem Ges 75 (1942) 350 (with pyridine.HCl, 200-220°C)
- J Chem Res Synop 6 (1999) 394 (pyridine.HCl, microwave)
- Synthesis (4) (1985) 437 (AlI3, PCT)
- Tetrahedron Lett 38(50) (1997) 8749 (1-methyl-2-pyrrolidinone)
I guess that the AlI3 method is one of the easiest ones. Check out

Post 422757

(GC_MS: "Aluminium iodide in ether cleavage", Methods Discourse)
on how to make this otherwise very expensive compound yourself.

Monobromination of 4-hydroxybenzaldehyde:
- Tetrahedron Lett 21 (1980) 4931 (Br2)
- Arch Pharm 322 (1989) 477 (Br2, HOAc)
- Tetrahedron Lett 34 (1993) 7401 (Br2, CHCl3)
- Ber Deutsch chem Ges 28 (1895) 2410 (Br2, discusses dibrominated product as well)

Synthesis of 3,4-dihydroxybenzaldehyde:

Patent DE082078

(NaOH, 150-200°C)

Patent DE269544

(NaOH, Cu, pressure)
- Kogyo Kagaku Zasshi 47 (1944) 168 [CA 1949 1974] (NaOH, Cu)

Methylenation of 3,4-dihydroxybenzaldehyde is explained at Rh's website. Please refer to

Iodination instead of bromination should work as well, I guess.

Voila, hopefully somebody sees something interesting in this. I am still convinced that vanillin is an easier precursor, which is equally unwatchable as anise oil. Good luck  ;) .

A fellow bee already proposed the following: Isn't the demethylation of 4-methoxy-benzaldehyde much easier than that of vanillin, making it possible to use refluxing 48% HBr (possibly with a PTC) for the ether cleavage step? As the molar weight of AlI3 exceeds 400, you need quite a lot of that to run a molar batch. After the reaction you just distill off the HBr azeotrope for reuse. Or - maybe it would be possible to add some H2O2 after the demethylation to make Br2 in situ and make the 4-MeO-BA -> 3-Br-4-OH-BA transformation a one-pot reaction. In that case the product is extracted with DCM, any residual bromine reduced with sulfite/phosphite or whatever, followed by recovery of the azeotrope.

So, the aim of this thread is to combine The Hive Brains in an attempt to find a profitable way of turning anise oil into MDMA. It's not sure that this contest will end with good results, but as I know from my experiences in real life, you never know the outcome if sexual compensation is offered as reward. Theoretical AND practical information/remarks are welcome. Note that the given references are just leads and that there might (and most probably will) be better solutions. It would be a nice thing if this thread could be concluded with the sentence on the back of Strike's TSII.


  • Guest
anethole to isosafrole?
« Reply #1 on: July 03, 2003, 03:23:00 PM »
Any chance of employing anethole in place of eugenol in

Post 381882

(GC_MS: "Eugenol -> elemicin and myristicin", Novel Discourse)
Anethole to ‘anethole-5-carboxaldehyde’ then to 5-hydroxy anethole, then ether cleavage, then to isosafrole?

I imagine the yields would be dismal.


  • Guest
very low
« Reply #2 on: July 03, 2003, 03:56:00 PM »
The yields would be extremely low, but it is very good you remind me of this possibility.

Demethylation of anethole to anol (4-hydroxypropenylbenzene) can be accomplished in several ways, but they all have one thing in common: low yields, or nasty procedures. It is advisable to use anol instead of anethole in the Duff formylation step if you want a yield higher as 1% as well...  :)
I looked it up once, and gave it up as well. Very frustrating, very poor yield. I can - if you want - dig up the notes I made about it (if I didn't throw them away, that is  ::) ).


  • Guest
« Reply #3 on: July 03, 2003, 04:21:00 PM »
I can - if you want - dig up the notes I made about it (if I didn't throw them away, that is  ::) ).

If it’s not too much trouble – I would appreciate it greatly. I meant to look into it ages ago, but never got around to it.

I may have to do some searching of my own too - anethol does deserve attention  :)


  • Guest
Some random notes
« Reply #4 on: July 03, 2003, 04:45:00 PM »

Patent US2394565

- Describes the demethylation of anethol using Grignard reagents. Contains several examples.

Monatsh Chem 35 (1914) 332 and Monatsh Chem 36 (1915) 6 - Same reaction (Grignard), using ethylmagnesium iodide.

JCS Perkin Trans 1 (1981) 897 - Uses MeMgI and has 13% yield.

Ber Deutsch chem Ges 74 (1941) 1219 - Describes demethylation with pyridine.HCl at reaction temperatures of 200°C and more. See also Ber Deutsch chem Ges 75 (1942) 350.

About the Duff-formylation: I can't find my notes on that reaction specific for anethole, but I do remember that the yields were low enough for me not to endeavour this reaction any further. But the reference was an old one. In the mean while, there have been

some improvements

( and after all, hexamine is extremely cheap.


  • Guest
The diazotation pathway
« Reply #5 on: July 10, 2003, 01:18:00 AM »
I proposed that 3,4-dihydroxybenzaldehyde could be prepared if 4-hydroxybenzaldehyde would be halogenated (bromination/iodination), but there is  another way of incorporation of the hydroxy group, viz via diazotation.

For this purpose, 4-hydroxybenzaldehyde has to be nitrated. Obviously, 4-methoxybenzaldehyde can be nitrated as well, but there are some things to keep in mind... When 4-hydroxybenzaldehyde dissolved in GAA is treated with an excess of HNO3, 3-nitro-4-hydroxybenzaldehyde is the only reaction product which has been found at the end of the reaction.1 However, when 4-methoxybenzaldehyde is subjected to a nitration reaction (nitration:sulfuric acid mixture 1:20), then 3-nitro-4-hydroxybenzaldehyde is the only product when working at sub-0°C 2; but at temperatures higher as 0°C, 3,5-dinitro-4-methoxybenzaldehyde and 2,4,6-trinitrobenzene are present as well.3

1. C Paal. Ber Deutsch chem Ges 28 (1895) 2413
2. A Einhorn, JP Grabfield. Ann 243 (1880) 370
3. E Woerner, Ber Deutsch chem Ges 29 (1896) 157; F Mauthner. J prakt Chem [2] 104 (1922) 132.

Reference: Houben-Weyl. Stickstoffverbindung I, Teil 1.

I have took a plunge into the printed version of Beilstein (massive piece of work...).

3-nitro-4-methoxybenzaldehyde - Can be obtained by boiling of the benzaldehyde's diacetate in 5% sulfuric acid (De Lange, R 45, 46). Can also be synthesized by nitration of anisaldehyde (Pfeiffer, Ann 460, 190; Mauthner, J prakt Chem [2] 104, 133). The benzaldehyde yields its diacetate when treated with Ac2O. For colour reactions, see Shoesmith. Soc (1927) 2223.

3-nitroo-4-hydroxybenzaldehyde - Can be obtained by oxidation of the corresponding benzyl alcohol in an alkaline permanganate solution (Fishman, JACS 42, 2229). It forms needles from water. A mixture of HNO3 and sulfuric acid give picric acid. The same substance in combination with 3,5-dinitro-4-hydroxybenzaldehyde can be synthesized by treating 4-hydroxybenzaldehyde in 98% HNO3 at 5-10°C (Hodgson, Soc (1927), 2379).

Ber Deutsch chem Ges = Berichte des Deutsche chemischen Gesellschaft
Soc = Journal of the Chemical Society
JACS = Journal of the American Chemical Society
Ann = Justus Liebigs Annalen der Chemie
J prakt Chem = Journal fuer praktische Chemie
R = Recueil des Travaux Chimiques des Pays-Bas


Post 429604

(GC_MS: "translation", Chemistry Discourse)

Old articles from Berichte der Deutschen chemischen Gesellschaft and Journal fuer praktische Chemie may be retrieved via

the Gallica website



  • Guest
flourinate a hydroxyl
« Reply #6 on: July 27, 2003, 02:42:00 AM »
Can one halogenate the HO on the ring???


  • Guest
i shoulda won
« Reply #7 on: October 06, 2004, 02:08:00 AM »
anethol + koh ---> anol  fieser & fieser organic synth
anol + hexamine ---->  4-anol aldehyde
4-anol aldehyde + h2o2 + NaOH ---> 3,4 hydroxy propenylbenzene
3,4 hydroxy propenylbenzene + NaOH ---> 3,4 sodium propenylperoxyphenyl (name may be wrong but it works boil it dry to a salt)
sodium salt of 3,4 hydroxy propenylbenzene + dcm in acetone
---> iso saf ye baby