Anise oil as PMA precursor

[Jackhammer]

Anise oil as para-methoxyamphetamine (PMA) precursor
D. Waumans, N. Bruneel, J. Tytgat
For. Sci. Int., 133 (2003) 159-170
DOI:

10.1016/S0379-0738(03)00063-X

Abstract
These days, MDMA is one of the most popular drugs of abuse. Due to its illegality, MDMA and its chemical precursors are watched by governmental organizations in many countries. To avoid conflicts with legal instances, underground chemists have tried to market several new unregulated amphetamine analogues, such as 4-MTA. Para-methoxyamphetamine (PMA), on the other hand, is regulated by law but its precursors are easily obtained since they are cheap and unwatched. This article presents such a case, namely the large scale synthesis of PMA using anethole, a main constituent of anise oil, as precursor. Anethole has been converted to its phenyl acetone analogue via peracid oxidation, while PMA itself has been synthesized using this ketone as precursor in the Leuckart synthesis. The synthesis of PMA using anethole as starting product has been investigated applying GC/MS and GC-HSPME/MS techniques, hereby discovering new specific (4-methoxyphenol) and already identified synthesis impurities (4-methyl-5-(4-methoxyphenyl)pyrimidine, N-( -4-methoxyphenylisopropyl)-4-methoxybenzyl methyl ketimine, 1-(4-methoxyphenyl)-N-(2-(4-methoxyphenyl)-1-methylethyl-2-propanamine, 1-(4-methoxyphenyl)-N-methyl-N-(2-(4-methoxyphenyl)-1-methylethyl-2-propanamine, N-( -4-methoxyphenylisopropyl)-4-methoxybenzaldimine). The new impurity 4-methoxyphenol is specific for the application of a peracid oxidation method where anethole is used as precursor.

[Rhodium]

Forensic Sicence International 133, 159-170 (2003)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/forensic/anethole.pma.precursor.pdf)

[senzualus]

I think it's a great idea (at least for me) since in my country -one ex communist, non USSR, little country in eastern Europe- the public perception of drugs is: "drugs=heroin , something you inject in your veins an makes you do crazy things".

Besides that I don't think the law authority here makes much difference between the various substituted amphetamine derivates and MDMA -they recently (a couple of months ago) put safrole on the precursors list...

.... so you can get 10ml freshly squeezed, fennel oil(~90% anthole) for about 1.5$ from the "aromatherapy, natural stuff & more" store (among other oily, goody-smelly things )...I don't know about you, but for my needs is just perfect  

my experiments:

anethole--(Br₂/bromhydrin/epoxide oxidation)-->ketone

the ketone -(NH₄Cl/NaOH Al/Hg)-> amine reaction was a failure (I really don't want to talk about that)

any refs and sugestions are welcome....

[GC_MS]

any refs and sugestions are welcome....

Read CA, it's FULL with references to anethole.

... so you can get 10ml freshly squeezed, fennel oil(~90% anthole) for about 1.5$ from the "aromatherapy, natural stuff & more" store (among other oily, goody-smelly things )...I don't know about you, but for my needs is just perfect

Wrong, fennel oil contains much less anethole: 50-70%. Anise oil derived from Illiceum verum and Pimpinella anisum is what you need (80-95%). Or should I say "need". I never understood why somebody wants to take PMA deliberately if he/she has experienced the effects before. I tried the drug only twice (I guess about 4 years ago), and brought back the memories of bad trips. It caused serious overheating and a flood of sweat. Very unpleasant. Now, I only have a small bottle of sweet anise left, just for its odor.

[java]

One can also add methylamine to the allene in the presence of a catalytic amount of CuBr. or palladium compounds.  That would make P-methoxy Methamphetamine. What I like to know is how  to remove the methoxy or change it to a less inactive component or get rid of it ......java

[senzualus]

I've read some reference about cleavege of the methoxy group here on the hive (it was somthing about eugenol I think...?)
It was a method involving AlCl₃ I guess...

I'll get back to you on that...

[GC_MS]

You can convert anethole to anol using several methods, but they usually give low yields. I'm not sure AlCl3 (or AlI3) will work for anethole, since I'm affraid a Friedel-Crafts polymerization reaction might kick in.
However, conversion of p-methoxybenzaldehyde to p-hydroxybenzaldehyde is feasible if you have aluminium foil and I2 crystals (AlI3 is a very good ether cleavage Lewis acid; e.g.

Post 422757

(GC_MS: "Aluminium iodide in ether cleavage", Methods Discourse)). In a pure theoretical way, p-hydroxybenzaldehyde is a gateway toward two classes of goodies:
1. by monobromination of p-hydroxybenzaldehyde, 3-bromo-4-hydroxybenzaldehyde is obtained. What happens if the bromo group is substituted for hydroxy? Yup, correct. But I don't understand why one would try this alternative though. Vanilline is much easier and requires less hazardous chemicals (like the bromine).
2. by dibromination of p-hydroxybenzaldehyde, a precursor for 3,4,5-trimethoxy and triethoxybenzaldehyde is obtained. p-Methoxybenzaldehyde can be dibrominated as well, wich might be an interesting precursor for EME.

All pure theoretically though.

[senzualus]

about the use of lewis acids to cleave aryl methoxy groups...

I haven't tried it (and I don't know if anyone has) but maybe someday...

https://www.thevespiary.org/rhodium/Rhodium/chemistry/eugenol.mdma.html

[GC_MS]

I remember subjecting anise oil to a bromination reaction and had a yellow oil as result.

[hypo]

> ~100% anise was brominated.

how do you know?
weight increase? tlc? boiling point?

(can you try with KBr?)

[GC_MS]

Also, you should consider that - if not using pure anethole - that anise oil contains other components which also have (multiple) double bonds.

[senzualus]

In my experiments (not always so fortunate) I used Br₂ (not NaBr/H₂SO₄/DMSO).
I prepared the bromine using KBr and H₂SO₄ added from a dropping funnel. The flask containing KBr was slightly heated and the bromine vapours were colected through a glass tube (use rubber tubing just for the joints 'cause the bromine will turn it into breakable shit and may cause plugging) into an ice cooled flask.
You should also be careful because of bromine vapours that are quite nasty (take my word for it).
In the articles I've read the bromine solution (in DCM, CCl₄, or naphta lighter fluid) was added to the anethole.
In my case I did just the opposite (I'm not so keen on handling bromine in confined space)- I've added a solution of anise oil in DCM to a bromine solution (also DCM) using an addition funnel.(I've read bromine, also idine and chlorine, reacts quikly in DCM, CCl₄, and naphta).
During addition the color remained the same(dark brown-red). At the end upon stiring the solution became slightly reddish, there was a sudden release of some gas (vapors of somekind???), and the solution became a little warm.

And that's about it....

You can read more somewhere on rhodium's page and probably here at the hive as well.

...so....post your results  

[senzualus]

also about anise oil becoming magenta - it happend to me to
and I thought it was somekind of reaction (polymerisation) cause by the conc. sulfuric acid...I don't know...

[hypo]

you made dibromo anethole, doofus    

[senzualus]

https://www.thevespiary.org/rhodium/Rhodium/chemistry/mdp2p.dibromide.html

anethole --Br₂--> dibromide >bromohydrin >epoxide >ketone ---NH₃/Al/Hg---> PMA

https://www.thevespiary.org/rhodium/Rhodium/chemistry/tcboe/index.html

- chapter5

That was the general idea and in my case is much more
aplicable since DMSO and DMF are not accesible.

https://www.thevespiary.org/rhodium/Rhodium/chemistry/epoxide.html

- epoxides from propenylbenzenes - someone might find it useful...I guess

[hypo]

that sounds like a painful way to PMA  

oh, and btw, the NH3/Al/Hg doesn't work. utfse.
(rhodium: does "Nichols et al, J. Med. Chem., 29, 2009-2015 (1986)." really prepare
MDA with NH3/Al/Hg like stated in TCBOE? if not, how about adding a big red warning
to the passage that says so?)

[Rhodium]

J. Med. Chem., 29, 2009-2015 (1986)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/nichols/nichols-mbdb-bdb.pdf) is about the synthesis of MBDB and BDB (the alpha-ethyl homologs of MDMA/MDA), and only the N-Methylated amine is made by Al/Hg reductive amination, the primary amine is made from NH₄OAc/NaBH₃CN - yet again TCBOE is at fault.

I'd really like to have warnings added to the many incorrect passages of TCBOE, but I'd like to have it done thoroughly then - if only a fraction of the glaring errors are commented upon, people are probably more likely to assume that the rest is fully correct.

Would you like to help me go through the entire book and write correctional footnotes, so that I can insert them in the documents later?

[Vibrating_Lights]

HOw can anyone here even talk about making this primary amine after all the toxic reports.  HOwever as i have been saying for a while. The n'methyl derivitive is awesome. 

The Para methoxy group is not very prone to polymerization with any of the peracid reactions.  Reactions to the ketone that involve the glycol are slightly lower yeilding than reactions that procede through the epoxide.  This may be due to the fact that the reactivity of the peracid is lower in reactions that procede throught he epoxide due to the conditions nescesary for it formation. 

IN swims experience the best method for producing the ketone is VIa the MeCN/MeOH/H2O2 Method.

This is a rediculas almost one pot to the ketone.

This is how it goes. FIll in your own ammounts
__________________________tearhere_________________________

Alkene to Solvent    V/V  Alkene:MeOH:MeCN:H2O2     PH 8.8
                             1  :  5 : 5             *NaCO3
Alkene to Oxident    M/M     1  : -------- 1.13

------------------------tear here--------------------------

Add all reactants together with the exception of the H2O2
Use enough sodium carbonate to make the reaction have a PH of 8.8 The sodium carbonate will not dissolve.  The add your 35%H2O2.  Stirr this for 24hrs at room temp.

After 24 hrs has elapsed filter the solution to remove the Sodium Carbonate. Then place this on some heat and distill off all the MeCn/MeOH.
WHen the temp starts to climb past 80 or so Change recieving flasks and keep the MeOH/MeCN to use on the next run. Keep the temp at 100 till the waters gone from the 35%H2O2.
Now rotate the rig so the condensor is slightly inclined like a reflux condensor. now turn the heat up slowly till the epoxide starts to boil.  Watch the kneck of the flask to see when the drip back is ketone green.  hold it here for a few minutes then turn the conmdensor downward and slowly distill the ketone at atm pressure. there is no other fraction that comes over.  It is actually not epoxide that is boiling at first but ketone that was just formed.  the Bp Of the ketone is lower than that of the epoxide.  If you do your distillation slowly no epoxide will make it over as it is converted to ketone before it reaches it's boiling point.  Yeild from 170gms raw oil was 140gms.  Reductive aminations with nitromethane yeilded 75-80%with ketone made ni this manner; 80-85%with MeAm and NaBH4.

4MeO'NN'Diethylamphtamine has also been syhthesized in good yeild from this ketone with NaBH4.  Pending BioAssay.

Anethol is also a good starting point for some interesting trisubstituted amphetamines.
Take for example 3,5bromo,4 methoxy amphetamine:  Compare this to 4 bromo2,5dimethoxyamphetamine.  I am not aware that this compound ha sbeen explored yet but i would likely guess that they would be very similar.
  One bee has sampled the dibrominated N'Methyl analog and is preparing a report to the future. All you get now is that he was estatic.  The Amphetamine is in line for synthesis next.
  The only other mention of dihalogenated methoxy compounds was by G-pig a few years ago.  He prepared the PEA and was also very excited about his findings. 
   The 4 position seems to be the most important position for substitution of the ring.  a resourceful chemist would somehow turn that methoxy into a single flourineMMMMMM yum.
Peace
VL_

[senzualus]

Well I guess someone should try and correct any mistakes found on Rhodium's....at least no one got hurt..
Since Al/Hg/NH₃ reduction does not work on the primary amine and works fine (at least so I've read) on N-methylated amine (as in some MDMA methods) I think it would work on a N-methyl PMA reaction.

So I have this in mind:
 anethole - Br₂ > epoxide > ketone
 ketone > MeNH₂ /Al/Hg > N-methyl PMA (as in "Osmium's variation on the Al/Hg reductive amination of MDP2P")

So...am I right ...
Please post any comments or experimental notes  

[Vitus_Verdegast]

Please post any comments or experimental notes 

I.  UTFSE!!!  N-methyl-PMA, or commonly called PMMA, has been fully covered here before. To obtain it just substitute the correct molar amount of anethole for isosafrole in a peracid, oxone,... oxidation, followed by a reductive amination of 4-MP2P with MeNO₂ or MeNH₂

II. I'd think twice about ingesting a substance like PMMA.
Read

PiHKaL #130

(http://www.erowid.org/library/books_online/pihkal/pihkal130.shtml) :

 In truth, METHYL-MA is a well studied drug, at least in animals. In both mice and rats, it is an exceptionally potent agent in creating the state of catatonia. Animal studies, prompted by the clandestine synthesis of METHYL-MA, have shown that there is indeed locomotor stimulation and some central effects, but these effects are somehow different than those of a simple amphetamine-like agent. The experimenter's conclusions, based on its structural resemblance to 4-MA and its proclivity to produce catatonia in some animal species and the ever-present possibility that there might be unsuspected neurochemical changes to be seen with its use, are that human experimentation should be discouraged. I have come to the same conclusion, but in my case this is based on a much more succinct observation: I tried it and I didn't like it.

and

None

(https://www.thevespiary.org/rhodium/Rhodium/pharmacology/pmma.txt)


Around here only V_L appears to like it.