What is wrong with the MDMA available today?

[Jabberwocky]

And? Unless the MDMA produces of today are using the EXACT same reaction conditions (solvents temperatures reagents and scale) as whoever used PMK glycidate in the past....the products produced could greatly differ....reaction conditions can totally change the game in chemistry....the fact that two different synths start with the same reagent means nothing

1. You obviously don't understand that PMK-gly is converted to MDP2P -- before anything else gets "in the flask"

2. Reaction conditions won't change the chirality of MDMA (because the conditions are highly conserved or the reactions won't work), perhaps a chiral catalyst, but there is no evidence of such.


FYI - MDP2P is not a reagent -- it is the substrate. Duh

 

[Jabberwocky]

The chances that an in situ chiral catalyst is forming from a non chiral catalyst by the glycidic impurity coordinating to the catalyst or the ketone before/during the reduction of MDp2p is very possible. There are many examples of forming in situ chiral catalysts by the pre mixing of a chiral ligand and an non chiral catalyst in the literature....tons of examples in all different kinds of catalystic chemistry including reductions

Not for the well characterized and well understood PMK-gly to MDP2P -- it has been known (and used) for decades, Shulgin even identified the piperonal pathway to MDP2P.

Furthermore, if anybody wanted to prove it out, simply take 10-20 of these suspect pills, and extract the alleged MDMA with acetone.

After washing and drying, first test by melting point -- then send for GCMS - to prove it is MDMA and nothing else.

Then convert to the freebase, then

put into solution with a chiral acid (like r tartaric acid) -- this will precipitate out one stereo-isomer.

If all the MDMA or none of the MDMA freebase precipitates out, there was only 1 stereo-isomer.

If not -- it was racemic

weighing the substances will show the racemic ratio

Simple.

 

[LucidSDreamr]

Not for the well characterized and well understood PMK-gly to MDP2P -- it has been known (and used) for decades, Shulgin even identified the piperonal pathway to MDP2P.

Furthermore, if anybody wanted to prove it out, simply take 10-20 of these suspect pills, and extract the alleged MDMA with acetone.

After washing and drying, first test by melting point -- then send for GCMS - to prove it is MDMA and nothing else.

Then convert to the freebase, then

put into solution with a chiral acid (like r tartaric acid) -- this will precipitate out one stereo-isomer.

If all the MDMA or none of the MDMA freebase precipitates out, there was only 1 stereo-isomer.

If not -- it was racemic

weighing the substances will show the racemic ratio

Simple.

nobody determines enantiomeric excess like this because its not reliable.....either chiral lcms is used or a mosher analysis.

 

[Jabberwocky]

nobody determines enantiomeric excess like this because its not reliable.....either chiral lcms is used or a mosher analysis.

1. it's HPLC not lcms -- and that brings a host of process issues like determining purity, solvent, adsorbent

you cant perform chiral HPLC without a purified substance to make the solute from, and an adsorbent that differentiates between isomers (do you know of one for MDMA ??)

2. Mosher analysis ( mosher's method)

requires a chiral derivatizing agent (a chiral acid) <<<Mosher's acid>>> or another chiral acid like r-tartaric -- gee where did we hear about r-tartaric acid? oh yeah it was in my example which is


a version of mosher analysis -- duh!

Thanks for supporting my example.

BTW -- my process won't cost the couple thousand for chiral column chromatography you would have to pay

 

[LucidSDreamr]

1. it's HPLC not lcms -- and that brings a host of process issues like determining purity, solvent, adsorbent

you cant perform chiral HPLC without a purified substance to make the solute from, and an adsorbent that differentiates between isomers (do you know of one for MDMA ??)

2. Mosher analysis ( mosher's method)

requires a chiral derivatizing agent (a chiral acid) <<<Mosher's acid>>> or another chiral acid like r-tartaric -- gee where did we hear about r-tartaric acid? oh yeah it was in my example which is


a version of mosher analysis -- duh!

Thanks for supporting my example.

BTW -- my process won't cost the couple thousand for chiral column chromatography you would have to pay

It didn't support your example at all....because the essence of a mosher analysis is differentiating the to enantiomers via NMR...it has nothing to do with weighing out amounts crystalized enantiomers....which is a highly unreliabe way to determine EE.....no chemist in the world determines ee by this approach....none...nobody does it.

Its chiral LCMS...not hplc. HPLC is for preparative purposes....LCMS is for analysis hplc is for prep work.

example of LCMS used in chiral resolution of amphetamine and methamphetamine with a chiral column....there are hundreds of different chiral stationary phases that can be used to resolve amphetamine enantiomers....and its done in human urine in this publication which is not purified drug...urine with tons of other drugs metabolites and protiens present in the mix...much more impure than an X pill....purification is not neccessary to determine EE vial chiral chromatography as you stated...especially with LCMS because the chromatography and mass spectrometry has such high specificity for your target it doesn't matter if its impure

http://sciex.com/Documents/Applications/RUO-MKT-02-0403_Amphetamine_chiral_final.pdf

 

[Jabberwocky]

It didn't support your example at all....because the essence of a mosher analysis is differentiating the to enantiomers via NMR...it has nothing to do with weighing out amounts crystalized enantiomers....which is a highly unreliabe way to determine EE.....no chemist in the world determines ee by this approach....none...nobody does it.

Its chiral LCMS...not hplc. HPLC is for preparative purposes....LCMS is for analysis hplc is for prep work.

example of LCMS used in chiral resolution of amphetamine and methamphetamine with a chiral column....there are hundreds of different chiral stationary phases that can be used to resolve amphetamine enantiomers....and its done in human urine in this publication which is not purified drug...urine with tons of other drugs metabolites and protiens present in the mix...much more impure than an X pill....purification is not neccessary to determine EE vial chiral chromatography as you stated...especially with LCMS because the chromatography and mass spectrometry has such high specificity for your target it doesn't matter if its impure

http://sciex.com/Documents/Applications/RUO-MKT-02-0403_Amphetamine_chiral_final.pdf

Mosher uses chrial derivatization, and was around long before nuclear magnetic resonance, hence "mosher's acid"

LCMS cannot determine chirality per your own citation:

" LC-MS/MS eliminates the need toderivitize and allows direct, 100 % detection. Mass spectrometryalone, however, cannot distinguish between stereoisomers,since it characterizes compounds solely in terms of mass."

Chiral Column HPLC is used to determine EE

 

[LucidSDreamr]

Mosher uses chrial derivatization, and was around long before nuclear magnetic resonance, hence "mosher's acid"

LCMS cannot determine chirality per your own citation:

" LC-MS/MS eliminates the need toderivitize and allows direct, 100 % detection. Mass spectrometryalone, however, cannot distinguish between stereoisomers,since it characterizes compounds solely in terms of mass."

Chiral Column HPLC is used to determine EE

you have no idea what you are reading or talking about....i'm not going to explain basic chemistry to you

 

[Jabberwocky]

you have no idea what you are reading or talking about....i'm not going to explain basic chemistry to you

Sure I do.

FYI - I quoted the paper you posted -- lol

LCMS -- is mass spectrometry -- it cannot determine chirality -- period (your own citation even says so)

Chiral HPLC can based on the difference in times the anaylte(s) leave the column

 

[LucidSDreamr]

Sure I do.

FYI - I quoted the paper you posted -- lol

LCMS -- is mass spectrometry -- it cannot determine chirality -- period (your own citation even says so)

Chiral HPLC can based on the difference in times the anaylte(s) leave the column

LCMS stands for Liquid Chromatography coupled to MAss spectrometry. It is the gold standard for determining ee in chemistry.

LCMS is an analytical HPLC sized column coupled to a mass spectrometer ....it is not a mass spectrometer alone which is what you seem to be confusing. In this case the LC would be a chiral LC


Any lab in the world you sent a sample to for determination of the enantiomeric ratio will use LCMS....not HPLC without an mass spectrometer. not hplc with any other kind of detector...any LCMS....let me say that again...they will use an L C M S

you just want to argue. If you walked into any lab in the world and said that LCMS can't determine enantiomeric ratios they would laugh

 

[Jabberwocky]

LCMS stands for Liquid Chromatography coupled to MAss spectrometry. It is the gold standard for determining ee in chemistry.

LCMS is an analytical HPLC sized column coupled to a mass spectrometer ....it is not a mass spectrometer alone which is what you seem to be confusing. In this case the LC would be a chiral LC


Any lab in the world you sent a sample to for determination of the enantiomeric ratio will use LCMS....not HPLC without an mass spectrometer. not hplc with any other kind of detector...any LCMS....let me say that again...they will use an L C M S

you just want to argue. If you walked into any lab in the world and said that LCMS can't determine enantiomeric ratios they would laugh

Chiral HPLC is a separate and effective process that does not include Mass Spectrometry.

sigma-aldrich HPLC only no MS fexofenadine chiral -- http://www.sigmaaldrich.com/technic...al/applications/chiral-hplc-fexofenadine.html

I guess sigma-aldrich has an entire Chiral HPLC (sans MS) line of services for no reason

 

[consumer]

Seems like you are not open to the possibility of a different racemic mix of mdma being produced despite all the anecdotal complaints, the high dosage in the pills, and people like biscuit offering reasonable theories about why this is happening. You may think the mdma has not changed but many others think otherwise.

Clearly something is going on for so many people to be discussing it.

 

[LucidSDreamr]

Chiral HPLC is a separate and effective process that does not include Mass Spectrometry.

sigma-aldrich HPLC only no MS fexofenadine chiral -- http://www.sigmaaldrich.com/technic...al/applications/chiral-hplc-fexofenadine.html

I guess sigma-aldrich has an entire Chiral HPLC (sans MS) line of services for no reason

Your argument was that an LCMS cannot perform a chiral resolution and you need an HPLC to do it. by definition an LCMS is an HPLC + an MS as the detector. I don't understand what you were trying to argue....that and LCMS does not contain an HPLC and you need an HPLC instead/?

you can do a chiral resolution with an HPLC with another type of detector like UV vis....but maybe if you live in a third world country or 50 years ago you would do it like that....sort of like not using an NMR in a mosher analysis and trying to dtermine ee by crystalizing something out and weighing it. We are in the year 2016....we are not concerned with how things would have been done 50 years ago.

Its obvious from this and your previous argument about mosher esters that you jsut read stuff and argue based on statements you read without understanding what people actually do in chemistry in reality.

 

[Jabberwocky]

Your argument was that an LCMS cannot perform a chiral resolution and you need an HPLC to do it. by definition an LCMS is an HPLC + an MS as the detector. I don't understand what you were trying to argue....that and LCMS does not contain an HPLC and you need an HPLC instead/?

you can do a chiral resolution with an HPLC with another type of detector like UV vis....but maybe if you live in a third world country or 50 years ago you would do it like that....sort of like not using an NMR in a mosher analysis and trying to dtermine ee by crystalizing something out and weighing it. We are in the year 2016....we are not concerned with how things would have been done 50 years ago

1. -- MS by itself cannot determine EE, MS is not needed to determine EE -- MS adds nothing other than identifying the substance via mass

2 -- weighing it out after a mosher derivitization by using a chiral acid to precipitate freebase doesn't require a lab, is very cheap, and would be sufficient to resolve the "mostly r-isomer" argument

 

[Jabberwocky]

Seems like you are not open to the possibility of a different racemic mix of mdma being produced despite all the anecdotal complaints, the high dosage in the pills, and people like biscuit offering reasonable theories about why this is happening. You may think the mdma has not changed but many others think otherwise.

Clearly something is going on for so many people to be discussing it.

The only data regarding dose in pills is limited to Zurich, Bern, Vienna and Austria -- as far back as 2015 -- there is no data identifying mg content of any other MDMA containing pills on e-data from Jan 2015 to the present

the theory proposed regarding PMK-gly is not reasonable -- MDP2P is MDP2P -- the catalyst for PMK-gly to PMK is not a chiral catalyst

 

[LucidSDreamr]

The only data regarding dose in pills is limited to Zurich, Bern, Vienna and Austria -- as far back as 2015 -- there is no data identifying mg content of any other MDMA containing pills on e-data from Jan 2015 to the present

the theory proposed regarding PMK-gly is not reasonable -- MDP2P is MDP2P -- the catalyst for PMK-gly to PMK is not a chiral catalyst

You aren't grasping the theory correctly....We are talking about the reductive amination of MDp2p to MDMA....this is the step under question. It is likeley that purification does not happen during any of the steps...as most process scale syntheses go There by leaving a glycidic impurity present during the last step of the synth

 

[LucidSDreamr]

1. -- MS by itself cannot determine EE, MS is not needed to determine EE -- MS adds nothing other than identifying the substance via mass

2 -- weighing it out after a mosher derivitization by using a chiral acid to precipitate freebase doesn't require a lab, is very cheap, and would be sufficient to resolve the "mostly r-isomer" argument

1) show me where I suggested using a mass spectrometer without a chromatography setup up?

2) weighing out a mosher derivitization? lol bro if you only knew how stupid that sounds. I"m done with you man, go back to studying undergraduate organic chemistry for your final

 

[Jabberwocky]

2) weighing out a mosher derivitization? lol bro if you only knew how stupid that sounds. I"m done with you man, go back to studying undergraduate organic chemistry for your final

Are you saying it would not work? or it's low tech?

If the HPLC/MS process you propose is so great -- analyze a pill with it -- oh what? you don't want to spend the $$ or get caught?

 

[JBrandon]

, go back to studying undergraduate organic chemistry for your final

I don't really care much about this little tiff you guys are having, but I just wanted to say this cracked me up

 

[Biscuit]

It may be cheaper to use a catalytic reductive amination because it gets higher yields under the conditions of this process synthesis. Also it may be a very cheap reduction catalyst thats forming an in situ chiral catalyst via coordination of a glycidic impurity to the metal mechanistic organic chemistry can be much more complicated than making assumptions that limit what can be happening in the reaction mixture, I don't think you're giving the complexity of what can be happening with every thing in the flask enough credit....maybe this in situ chiral catalyst only gives a slight enantiomeric excess....nobody is saying that it gives pure R stereoismer...just a ratio that isn't 5050

Another possibility:
Somewhere along the reaction you now have significant amounts of r and s mdma forming.....plus a chiral glycidic impurity...plus more unreacted mdp2p....which is 2 chiral materias that could be doing some 3rd order process with the mdp2p favoring a chiral glycine/R(orS)MDMA/mdp2p intermediate....which produces more R or S mdma preferentially because it forms a more active catalytic species or lower energy transition state. the reaction order can get even higher also....this is just given as an example to show how complex mechanisms can be and there are plenty of studies showing how complicated catalysis really is and not a simple 2nd order process like people assume

Another possibility;
the chiral glycidic impurity could corrdinate to the Mdp2p oxygen...activating it for reduction and making it a chiral substrate favoring the formation of r or s mdma.

I agree with all of this and don't have anymore to say to add to the tiff.

 

[Jabberwocky]

You aren't grasping the theory correctly....We are talking about the reductive amination of MDp2p to MDMA....this is the step under question. It is likeley that purification does not happen during any of the steps...as most process scale syntheses go There by leaving a glycidic impurity present during the last step of the synth

They manage to get extremely pure MDMA into pills -- but don't practice good chemistry anywhere else along the way -- oookay.

Ok. Really? -- Lets talk actual compounds. !!! Glycidate = glycidic acid NOT the amino acid glycine !!!

1. PMK-glycidate is a powdered carboxylate (glycidic acid reacts to form either epoxides or carboxylates)

2. PMK (MDP2P) - is a liquid ketone

3. Why would you believe there is any significant amount of a glycidic impurity in the liquid MDP2P? -- that begs credulity. they can't decant a liquid, and then use a filter? really? really??

4. Any glycidic impurity would be a carboxylate or an epoxide.

5. Please identify the supposed possible epoxides or carboxylates that will interfere with the chirality of the ENTIRE MDP2P -- Nitromethane or MDP2P -- Methylamine reaction (instead of the molar fraction of the proposed impurity). It is chemistry, there are a finite set of epoxides and/or carboxylates that could possibly form.

6. Since you propose they don't purify anything -- where are all the epoxide and carboxylate reaction products?


What's more likely -- and actually plausible:

Someone may have synthed a giant batch of r-MDA -- there is a known synthesis to create the r-isomer as it is the supposedly "desired" isomer for MDA

Then, someone performed the PIHKAL MDMA synthesis from the r-isomer MDA and ended up with a ton of r-MDMA.