What is wrong with the MDMA available today? - v2

[4DQSAR]

@vash445 Believe me, I've also heard rumours but it's beyond general chemistry. But not 'F glycidate'?

I wonder if cinnamic acid / 3,4-methylendioxycinnamic acid derivatives are the starting point? After all, both are cheap and common in China.

CN Patent 109534970A details the benzaldehyde from the cinnamic acids.

I still think the 'secret ingredient' is SCALE. Once hobbyists would make a couple hundreds of grams of MDMA and think it a pretty good week. Now it seems like industrial processes have been adapted.

Those impurities that were later largely overcome suggests that SOMEONE is continusally working on telescoping the process.

 

[vash445]

@vash445 Believe me, I've also heard rumours but it's beyond general chemistry. But not 'F glycidate'?

I wonder if cinnamic acid / 3,4-methylendioxycinnamic acid derivatives are the starting point? After all, both are cheap and common in China.

CN Patent 109534970A details the benzaldehyde from the cinnamic acids.

I still think the 'secret ingredient' is SCALE. Once hobbyists would make a couple hundreds of grams of MDMA and think it a pretty good week. Now it seems like industrial processes have been adapted.

Those impurities that were later largely overcome suggests that SOMEONE is continusally working on telescoping the process.

It was f glycidate because it was so cheap..

Granted a liter of safrole can be had for $20-50 a liter.

 

[unodelacosa]

1 — Postimages

postimg.cc

Voila.

Interesting that people were so keen to argue the toss without even appearing to understan the chemistry.

Speaking of chemistry, this is not safrole, aka: 3,4-methylenedioxyallylbenzene, above. Safrole looks like this:

Notice where the double bond is. Also there's no such thing as "pipeerinol", but I think you meant "piperonal", aka: heliotropin, which looks like this:

You were much closer on this one.

It seems that @vash445 has much more intimate knowledge of what is actually going on in current MDMA production that anyone else I've talked to

That's one hell of a distinction to lay on a person publicly. Probably something best not to be declared, particularly when you still have some fundamental misunderstandings of the chemistry, demonstrated by this link you shared with the labels "MD methyl glycidate" and "MD ethyl glycidate", neither of which are real things. What you mean is "3,4-MDP-2-P methyl glycidate" and "3,4-MDP-2-P ethyl glycidate", and neither of these is represented by the bizarre-looking pseudo-chemical structures in the image.

It's worth reading the above paper.

All due respect, It's worth reading, studying and understanding this subject more thoroughly before littering the thread with bad intel and incorrect assumptions based on your limited understanding of organic chemistry, clandestine practices and psychoactive drug manufacturing.

MDMA derivatives that have chlorinde and or bromine ions on the aromatic ring. So they become part of the very MDMA molecule itself

These compounds you mention are distinct and separate compounds entirely from MDMA. In other words, 2-Br-3,4-MDMA is not the same compound as 3,4-MDMA. We're discussing the latter, not the former.

But double that because the -Br ions can just as easily be -Cl ions.

Or Fl atoms or a number of various moieties/molecules. Hence the broad scope and expanse of the compounds presented and discussed in PiHKAL and TiHKAL.

Then consider the mixtures of disubstitutions (8) and trisubstitutions (8) and in fact, that's a LOT of different impurities.

These are substituted analogs, which when unwanted can be thought of as "impurities", but probably more accurately should be considered active side-products of synthesis.

I think that's a very important detail. It seems like MDMA producers are going from precursors to pre-precursors and now to pre-pre-precursors.

This is neither accurate nor the right way to view the subject. It risks leading to unscientific and inaccurate theories that cause widespread misunderstanding, hysteria, and openly idiotic legislation. There are myriad ways to synthesize MDMA, and of course the rules of crapitalism and the obvious appeal of simplicity make it so that producers will seek the most cost efficient and simple methods available, all other factors being equal like risk and feasibility. Used to be in the 1960s and 1970s, one could order compounds like PMK (aka: 3,4-MDP-2-P) and BMK (aka: phenyl-2-propanone or P-2-P) directly to their residence under the masquerade of being a legit company, and there were hardly any questions asked.

By the 1990s, legislation eventually passed and the DEA setup a list of precursor items that chemical suppliers were required to report to DEA or face consequences. This included items like PMK which they had recovered from busted clandestine labs. So producers moved to obtaining safrole and isosafrole, including natural sources for them like sassafras oil. So with the help of the FDA, DEA had sassafras oil banned for human consumption and they started monitoring all other sales of the product. Safrole converts to isosafrole and then to PMK before reducing to MDMA (or MDA, MDE, et al). This is more-or-less a 2- or 3-step synthesis.

BUT THEN, producers moved back in the other direction when they started ordering PMK glycidate, aka 3,4-MDP-2-P glycidate, which cleverly skirts the ban on 3,4-MDP-2-P. Removing the glycidate molecule is a piece of cake compared to working safrole up to PMK, so this is—at most—a 2-step synthesis, arguably easier than the previous major synthetic routes.

Then there's the route from heliotropin. They're all just different approaches to the same end result, and when properly purified and worked up, they will produce the same product. Any trained chemist worth their salt will attest to this.

Put simply, people make MDMA for MONEY.

Or for their own personal use with various reasons and motivations behind said use, but yes I agree that money is the main motivation. Clearly, virtually every drug, legal or illicit, is being produced primarily for money. In fact, the motivation for the production of practically any product or service in a capitalist system is: money… more precisely: profits… or most precisely: increasing owner's equity in the enterprise selling said goods or providing said services.

If [MDMA producers] can find a cheaper route, they will ALWAYS use that cheaper route.

Just because they can find a cheaper route doesn't necessarily mean they will use it. There are other factors like: are all the precursors and reagents for a cheaper route actually available to them, and how easy and safely can they be procured? If risk is added, does the savings from the cheaper route justify its adoption? Does the cheaper route produce any differences in product in terms of chirality or potentially difficult-to-remove impurities and/or byproducts?

And let's be careful with the word "always" which is rarely the actual case IRL.

Grisham's law demonstrates that such will always be true. You can always sell your product for less than someone with higher costs.

Again with the "always". This statement also fails to consider sales volume and how setting price to optimize this volume results in higher net profits and maximizes the increase to owner's equity.

 

[4DQSAR]

It was f glycidate because it was so cheap..

Granted a liter of safrole can be had for $20-50 a liter.

Well I posted a link to that extremely extensive article which actually looked and the impurities found in MDMA samples and no mention of the glycidate esters were made.

I just remembered another article in which there was a lot of deforestation in Vietnam and Laos being carried out illegally by Chinese companies. So it seems highly likely that safrole is still a major precursor. I noted that multiple other natural products bearing the methylenedioxy ring can be cleaved to piperonal and that was also covered by the paper.

Now IF benzodioxole was being used, it would explain why 'purple moonrock' turned up everywhere for a while but because it uses bromine and hypochlorus acid, the aromatic ring was being halogenated which would explain the funky colours.

But if safrole only costs $20--$50/l, reducing THAT cost would be almost pointless. It's the large amount of solvents that are inevitably used that would represent the bulk of the cost. It's not just the cost of the solvent, it's the fact that you need to use large vessels if you want to produce at scale and you need to recycle the solvents (read about 'solvent management') or dispose of them. Put into perspective, you use around 60 grams of solvent for each gram of product. So rather than focusing on the cost of reagents, check the prices of solvents. Reagents also need to be added to that cost. The paper suggests hydrobromic acid is used to produce bromosafrole and methylamine to produce the final product.

The main reason bromosafrole wasn't the most common route was that it required a large excess of methylamine - increasing the amount of solvent still more.

There are a few tricks one can apply at small scales. Methylamine can be made from nitromethane IF one uses the mercury/aluminium amalgam method - but that doesn't scale well. Now there is no reason why someone couldn't use a reduction JUST to produce methylamine, but guess what? MORE solvent.

Anyone who seeks to telescope the synthesis would look at solvent usage FIRST. If someone has found a way to use vastly less solvent, THAT would be the way to reduce costs. Far more than the ultimate precursor.

I took a look at the chemistry surrounding the glycidate esters and while there may well be some clever shortcuts to allow it's direct usage in MDMA synthesis - it's not actually that cheap to make. The Darzens condensation uses a reagent that while not costly, isn't dirt cheap.

I'm more tempted to think 'F glycidate' refers to a salt rather than an ester. IF methylamine could react directly with the epoxide (I have no proof that this is possible - but it balances), the product would be potassium 2-methyl-2-(methylamino)-3-phenylpropanoate (or whatever salt is involved). Decarboxylation would yield MDMA. BUT as I said, glycidate esters are a bit of a pain to make and I spent several hours searching even the most obscure papers). I just don't think it's the cheaperst route. Safrole --> bromosafrole --> MDMA is the cheapest.

 

[4DQSAR]

BTW the problem will come when a competing group adopts the same methodology as those producing moonrock - this it inevitable.

Finding a vastly cheaper way of making something is a GREAT way to make a lot of money in the short-term. But as soon as competition arrives, people who are prepared to forego profit to establish a market-share will sell the product at cost (or close to it). At 'pennies per dose', to make money, the scale has to be huge.

The fact that methamphetamine can be made from glycidate esters but we haven't seen the price of that collapse does re-enforce the detail that safrole is the precursor.

If someone were to find a dirt-cheap source of allylbenzene, meth would likewise cost pennies per dose. But that hasn't happened (AFAIK) which sugggests pseudoephedrine or maybe L-PAC are now the common precursors for that compound.

BTW L-PAC is legal and produced on vast scales via genetically modified yeast converting benzaldehyde IS interesting as 3,4-MD L-PAC would, in theory, offer another precursor.

 

[4DQSAR]

BTW one thing I cannot find is an example of AMMONIUM glycidate salts. It's more than likely that the methylammonium salt could be formed using, you guessed it, methylamine.

A rearrangement of THAT might well yield that intermediate I named - the one that produces MDMA upon decarboxylation.

A lot of chemisty is carried out by Chinese researchers - I can believe someone intent on making MDMA in bulk would PAY for such research and it would never see a translation into English.

 

[user666]

BTW L-PAC is legal and produced on vast scales via genetically modified yeast converting benzaldehyde IS interesting as 3,4-MD L-PAC would, in theory, offer another precursor.

Do you mean (L)-Phenylacetylcarbinol from Benzaldehyde ?
Do you mean "3,4-MD L-PAC" from Piperonyl Aldehyde by the same yeast ?

 

[4DQSAR]

Do you mean (L)-Phenylacetylcarbinol from Benzaldehyde ?
Do you mean "3,4-MD L-PAC" from Piperonyl Aldehyde by the same yeast ?

Piperonal is the common name for 3,4-methylenedioxy benzaldehyde. Sorry if that wasn't clear.

While nobody has 'officially' tried piperonal in place of benzaldehyde, I found research papers that demonstrated the same biosynthesis with various ring-substituted benzaldehydes to demonstrate the scope of the reaction.

To be clear, L-PAC is only cheap because the ambient temperature in some regions of India is ideal. No heating or cooling required - thus lower costs. It's also a process only used on a vast scale. I mean 50000l vessels. If I'm remembering correctly, the original method could produce 25g of L-PAC per liter but hybrid yeasts and the use of some related unicellular fungi pushed that up to 40 or 50g per liter.

It's very much an emergent technology and a LOT of research grants in India are given to people seeking to optimize the route.

 

[unodelacosa]

Piperonal is the common name for 3,4-methylenedioxy benzaldehyde. Sorry if that wasn't clear.

Aka: heliotropin

To be clear, L-PAC is only cheap because the ambient temperature in some regions of India is ideal. No heating or cooling required - thus lower costs. It's also a process only used on a vast scale. I mean 50000l vessels. If I'm remembering correctly, the original method could produce 25g of L-PAC per liter but hybrid yeasts and the use of some related unicellular fungi pushed that up to 40 or 50g per liter.

I could see this being the case.

It's very much an emergent technology and a LOT of research grants in India are given to people seeking to optimize the route.

No doubt. Relevant: https://pmc.ncbi.nlm.nih.gov/articles/PMC10533076/

Also relevant: https://www.deskera.com/blog/the-role-of-process-development-in-chemical-manufacturing/

 

[vash445]

I'm more tempted to think 'F glycidate' refers to a salt rather than an ester

No need for proline esterification if you look at the latest findings.

Or the other, not so recent finding of our cowboy.

Amino acid esterification and production of the HCl is actually quite easy... you just need thionyl chloride.
Or, dry HCl gas in your alcohol dissolved, simply dry with mol sieves then.
But as said, no need for that, please check the most recent papers that could be organised by some of our members.

There are actually many papers out there on the production of amino acid ester hydrochlorides.
And they work well as written, if you do them as written(eg with SOCl2).

helional to mdp2p it's been done officially

also Re: One-pot helional to MDP2P done, actually. (with analysis and photos).



Recently, Jamieson group discovered an one-pot approach for amidation of aldehydes that involved multiple steps. [117] The reaction initiated with aldehydes and o-nitro phenylhydrazines in DMF which interacted with each other at room temperature, led to in situ formation of corresponding hydrazones. Then KBr, oxone and potassium carbonate was added to the reaction mixture simultaneously and hydrazones were converted to highly reactive nitrile imine intermediates.. Nitriles react with Grignard reagents to form an imine salt intermediate, which, upon hydrolysis under acidic conditions, yields a ketone at least how I read it... or N-acyl to MDMA variation

In summary, we have developed a one-pot procedure that consists of five distinct steps for the synthesis of amide bonds directly from the requisite aldehyde in a formal oxidative process using readily available reagents. This involves the condensation of a simple 2-nitrophenyl-substituted hydrazine with an aldehyde, followed by KBr-Oxone-mediated bromination of the hydrazone intermediate. In contrast to our previous studies utilizing N-(2-nitrophenyl)-hydrazonyl bromides and tetrazoles as NI precursors, this process does not proceed via the anticipated formation of an HOBt-type active ester instead proceeding via a distinct reaction pathway. Upon the generation of the NI dipole under these strongly oxidative conditions, our observations suggest the formation of an acyl diazene species, which then serves as an activated N-acylating agent, allowing the synthesis of a small library of amide products and known drug procainamide

A one-pot procedure for the oxidative amidation of aldehydes via the in situ generation of reactive nitrile imine (NI) intermediates has been developed. Distinct from our progenitor processes, mechanistic and control experiments revealed that the NI undergoes rapid oxidation to an acyl diazene species, which then facilitates N-acylation of an amine. A range of substrates have been explored, including application in the synthesis of pharmaceutically relevant compounds.

https://www.researchgate.net/publication/380816481_One-Pot_Oxidative_Amidation_of_Aldehydes_via_the_Generation_of_Nitrile_Imine_Intermediates

 

[4DQSAR]

Oh there is a HUGE segment of chemistry devoted to the production of amino-acids.

But you can't just decarboxylate - you would have to reduce the carboxylic acid to an alkane. Not an easy thing to do.

That's the payoff with the glycidate esters. You DO decarboxylate and the product is the appropriate ketone.

 

[vash445]

You DO decarboxylate and the product is the appropriate ketone

Sorry maybe I was saying or thinking wrong... Or hell maybe i'm wrong now... but I was thinking to start?

think like Diethyl(phenylacetyl)malonate to P2P I guess? Not quite... Anyways best I got...

We next set out to determine the scope of the reaction by applying these conditions to various propargylic alcohols (Scheme 3). Pleasingly, a selection of different α,α-diiodo-β-hydroxyketones 3a–3 i could be obtained in moderate to excellent yield from the corresponding alcohols. As well as secondary alcohols, a primary alcohol (3c) could also be employed. Tertiary alcohols were not suitable substrates, though this is perhaps unsurprising given the large steric demands of the geminal diiodo unit. The reaction could also be applied to the synthesis of a diiodohydroxyester (3 i) from the corresponding alkynyl ether.

novel metal-free intramolecular oxidative decarboxylative coupling of primary α-amino acids with 2-aminobenzoketones with different quinazolines can be selectively obtained by various oxidants?

https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cssc.202100373

α‐Amino Acid Esters via Palladium‐Catalyzed Oxidative Amination of Vinyl Ethers Using Hydrogen Peroxide as Oxidant and Oxygen Source


Enantioselective Hydroalkoxylation of 1,3-Dienes via Ni-Catalysis Seems... interesting?

Through our independent investigations, we discovered a complementary and enantioselective Ni-catalyzed hydroalkoxylation of dienes. Petroleum feedstocks and readily available dienes can be transformed into chiral allylic ether building blocks with high regio- and enantiocontrol via Ni-catalysis under solvent-free conditions

https://www.researchgate.net/journa...1YmxpY2F0aW9uIiwicGFnZSI6InB1YmxpY2F0aW9uIn19



maybe α‑Acyloxylation ? Or am I wrong thinking I need... 1,2-diol? β-diketones, β-Enaminones,β-diketone compounds with nitriles to give enaminones ?



Perchloric Acid Adsorbed on Silica Gel (HClO4—SiO2) as an Inexpensive, Extremely Efficient, and Reusable Dual Catalyst System for Acetal/Ketal Formation and Their Deprotection to Aldehydes/Ketones
DOI:10.1002/chin.200720046



α‑Acyloxylation of Ketones/Cyclic Ethers Mediated by Hypervalent Iodine(III) Reagents as Oxidants and Nucleophilic Sources

Though I guess where i'm not thinking right is Secondary Amides with Enamines or Ketones

also this peaked interest of course...

1,3-Dioxanes, 1,3-Dioxolanes

Most interesting glancing is

Commercially available MSTFA [2,2,2-trifluoro-N-methyl-N-(trimethylsilyl)acetamide] is a highly effective TMS (trimethylsilyl) source for the convenient preparation of cyclic acetals under modified Noyori's conditions. The reactions proceeded smoothly under mild conditions, affording a wide range of the corresponding cyclic acetals with excellent yields in the presence of catalytic TMSOTf.
S. Radomkit, J. A. H. White, E. Chong, Y. Zhang, J. Org. Chem., 2024, 89, 5555-5559.

Reactions of β-diketone compounds with nitriles catalyzed by Lewis acids: a simple approach to β-enaminone synthesis


Using a photochemical method for acetalization of aldehydes under low-energy visible light irradiation, a broad range of aromatic, heteroaromatic, and aliphatic aldehydes have been protected under neutral conditions in good to excellent yields using a catalytic amount of Eosin Y as the photocatalyst. Even challenging acid-sensitive aldehydes and sterically hindered aldehydes can be converted, while ketones remain intact.
H. Yi, L. Niu, S. Wang, T. Liu, A. K. Singh, A. Lei, Org. Lett., 2017, 19, 122-125.


Ammonium salts that can act as hydrogen-bond donors exert a remarkable acceleration on the rates of the regioselective arylation of electron-rich olefins by aryl halides in ionic liquids and common solvents.
J. Mo, J. Xiao, Angew. Chem. Int. Ed., 2006, 45, 4152-4157.





A catalytic method has been developed, which allows aryl halides to couple with various electron-rich olefins to give 1,1 0 -substituted olefins. The palladium-catalysed coupling in ionic liquid solvent proceeds with high efficiency and remarkable regioselectivity without the need for any costly or toxic halide scavengers. Parallel to this, an environmentally-appealing method for the asymmetric reduction of ketones has been established, with which a variety of chiral alcohols can be accessed with high enantioselectivity in water with no need for any organic solvents. The same chemistry has been explored for the reduction of aldehydes, which is shown to be fast and highly chemoselective. These methods add new tools to the armoury of synthetic chemists.

Progress in Electrochemically Empowered C−O Bond Formation: Unveiling the Pathway of Efficient Green Synthesis


The invention provides a method for synthesizing alpha-iodo-beta keto acetal compounds, which comprises the steps of feeding enamine ketone containing N, N-disubstituted structure and iodine simple substance in 1:2 molar equivalents, adding alcohol as solvent and reactant, heating for reaction, and purifying by silica gel column chromatography to obtain target products; the product is characterized by an acetal having an iodo substitution in the alpha-position and a ketocarbonyl group in the beta-position. The method has the advantages that (1) the reaction does not need any metal catalysis or any additional organic solvent, the alcohol is a reactant and also acts as a solvent, and the atom economy is high; (2) the raw materials are simple and easy to obtain, and the reaction of the easily obtained enaminone and alcohol in the elemental iodine is adopted; (3) simple operation and good total yield.



I heard this is probably used or looks familiar or most common

Various types of carbonyl compounds are efficiently converted to their 1,3-dioxanes by the use of 1,3-bis(trimethylsiloxy)propane (BTSP) and a catalytic amount of iodine under essentially neutral aprotic condition.
B. Karimi, B. Golshani, Synthesis, 2002, 784-788.

A thiol-promoted site-specific addition of 1,3-dioxolane to imines through a radical chain process enables a metal-free and redox-neutral conversion of inexpensive materials to a broad range of protected α-amino aldehydes in very good yields using only a catalytic amount of radical precursor. Both the thiol and a small amount of oxygen from air are indispensable to the success of this reaction.
H. Zeng, S. Yang, H. Li, D. Lu, Y. Gong, J.-T. Zhu, J. Org. Chem., 2018, 83, 5256-5266.

Aliphatic and aromatic ketones can be directly converted into their corresponding α-chloroketone acetals in very good yields using iodobenzene dichloride in ethylene glycol in the presence of 4 Å molecular sieves at room temperature.
J. Yu, C. Zhang, Synthesis, 2009, 2324-2328.[/URL]

 

[4DQSAR]

Well, consider that phenylanaline is so close to amphetamine - and yet only a msall unmber of speculative routes have ever been suggested.


Even things like LiAlH4 will only reduce to the alcohol. That step is quite well known. But to reduce that alcohol? Vraxy ideas like HI - which I'm unsure even works.

So those glycidate esters are convenient - they yield the appropriate P2P without too much work and there is no shortate of routes for reductive amination.

 

[unodelacosa]

https://www.researchgate.net/publication/380816481_One-Pot_Oxidative_Amidation_of_Aldehydes_via_the_Generation_of_Nitrile_Imine_Intermediates

Interesting link.

That's the payoff with the glycidate esters. You DO decarboxylate and the product is the appropriate ketone.

Obviously.

I think we might be veering too far off topic. Remember to relate this back to harm reduction. I don't think some of these points are worth bee-laboring here if you catch my drift

 

[4DQSAR]

I couldn't quite figure out how the link could be practical - hey, maybe that's on me.

I think it's well worth systematically going through the various potential routes used by those who produce MDMA at large scales.

I think we now know why 'purple moonrock' was a thing. Why 'moonrock' at all is itself an interesting question. My best guess is that it's one HUGE crystal. The benefit being that if you just melt your product and place it in a large vessel, on cooling it will ALWAYS form a crystal. Even if it's not as pure. I don't mean it's dreck, but it's not as pure. It also means that the consumer knows that what they get is what was made - it cannot be cut. I've seen a few pictures that show the beautiful monoclinic crystals - that's VERY pure.

But I do have to ask if MDMA is the best product and/or is it the product that is the cheapest to produce.

Because someone really has telescoped down the synthesis to be as simple as possible.

 

[vash445]

I couldn't quite figure out how the link could be practical - hey, maybe that's on me.

I usually need photo's, or a cas.. so maybe this might help?

• This new method directly converts aldehydes into amides by exploiting the oxidative protocol involving the in situ generation of nitrile imine (NI) intermediates.
  
  
  
  

  One-Pot Oxidative Amidation of Aldehydes via the Generation of Nitrile Imine Intermediates - PMC

  A one-pot procedure for the oxidative amidation of aldehydes via the in situ generation of reactive nitrile imine (NI) intermediates has been developed. Distinct from our progenitor processes, mechanistic and control experiments revealed that the NI ...

  pmc.ncbi.nlm.nih.gov
  
  

 

[unodelacosa]

I think we now know why 'purple moonrock' was a thing. Why 'moonrock' at all is itself an interesting question. My best guess is that it's one HUGE crystal.

First you say we know, but then you say you're guessing. I haven't arrived at any conclusions regarding this other than it's mostly marketing re-rock moves. Some cuts co-crystallize, too, which is why contiguous crystal formation does not always indicate purity, though I will admit that it often times is a good start/sign. Nothing's guaranteed, and we still can't account for what pharmacological action would lead to consistent sub-par experiences for some people when taking what's presented as "MDMA".

But I do have to ask if MDMA is the best product and/or is it the product that is the cheapest to produce.

Interesting question, and while I wonder this too, I also wonder how in scope this question is in this thread… I'm just attempting to keep mods from redacting some of these recent comments with connections to the topic that aren't immediately obvious.

Because someone really has telescoped down the synthesis to be as simple as possible.

Reductive amination of the ketone to the product is already relatively simple. PCP precursors on the other hand are telescoped in a Grignard as I understand it. Indeed this leads to impurities, but judging on what seems most likely, I'm inclined to think the majority of active MDMA labs still operate in mostly predictable patterns w/known syntheses that remain difficult to disrupt due to the relatively simple structure of the molecule and its precursors + needed reagents compared to the vast majority of other drugs.

But maybe I'm wrong. What do you mean by "telescoping" here? How would this affect the safety profile and qualitative effects of the end product for consumers, and can you present hard evidence that this is the case and cause of "meh-DMA" anecdotes from some users?

EDIT: Not to discount conjecture, I just think it's worth keeping speculation separate from what we know and can prove. And I say this with all due respect and as a fellow speculator myself.

 

[vash445]

But maybe I'm wrong. What do you mean by "telescoping", how would this affect the safety profile of the end product for consumers, and can you present hard evidence that this is the case and cause of "meh-DMA" anecdotes from some users?

In chemistry, "telescoping" refers to performing multiple chemical reactions in a single reactor without isolating the intermediate products, aiming for efficiency and reduced waste.Continuous multi-step synthesis by extrusion – telescoping solvent-free reactions for greater efficiency†
Chemical manufacturing typically requires more than one step, involving multiple batch processes, which makes synthesis at scale laborious and wasteful. Herein, we demonstrate that several reactions can be telescoped into a single continuous process and/or be carried out as a continuous multi-component reaction (MCR), by twin screw extrusion (TSE), in the complete absence of solvent.

Continuous multi-step synthesis by extrusion – telescoping solvent-free reactions for greater efficiency

Chemical manufacturing typically requires more than one step, involving multiple batch processes, which makes synthesis at scale laborious and wasteful. Herein, we demonstrate that several reactions can be telescoped into a single continuous process and/or be carried out as a continuous...

pubs.rsc.org

Mechanochemistry can be employed to carry out chemical reactions whilst eliminating or reducing the use of solvents, thereby making chemical synthesis less hazardous and more economical.1Recently, this form of synthesis has been scaled up from batch ball milling experiments (typically ghr‐1 scale) to continuous processing using extrusion (kghr‐1 scale) (Figure 1).2 Extrusion is an umbrella term used to describe a family of techniques that involve the conveying of material through a confined space. As a result, both shear and compressive forces are applied to the material, which can in turn instigate chemical reactions and drive them to completion.3 Initially, Paradkar et al. reported the use of Hot Melt Extrusion (HME) for the formation of co‐crystals.4 Subsequently, we have reported the use of Twin Screw Extrusion (TSE) for the manufacture of Metal Organic Frameworks (MOFs)5 and Deep Eutectic Solvents (DESs).6 Due to the noted advantages of employing TSE for the synthesis of high quality materials, that in most cases did not
require post process purification, we recently extended the technique successfully to four types of organic condensation reaction (Knoevenagel condensation, imine formation, Michael addition and Aldol reaction) which were successfully carried out by TSE. In addition, the Michael addition was found to be chemoselective under these conditions.7 Herein, we report that multiple sequential reactions can be telescoped together into a single extrusion process. Reaction telescoping in general can have significant benefits as noted already in solution‐based Continuous Flow Technology.8 In particular we demonstrate the synthesis of a nitrile followed by a subsequent Michael addition. Furthermore, we demonstrate that such reactions can alternatively be combined into a single multi‐component process, which is arguably more efficient than telescoping. This has also been demonstrated through two further examples, one of which is the Petasis reaction, the first organic non‐condensation reaction to be conducted by TSE.

Rest could/should be used by someones dreams

 

[unodelacosa]

In chemistry, "telescoping" refers to performing multiple chemical reactions in a single reactor without isolating the intermediate products, aiming for efficiency and reduced waste.Continuous multi-step synthesis by extrusion – telescoping solvent-free reactions for greater efficiency†
Chemical manufacturing typically requires more than one step, involving multiple batch processes, which makes synthesis at scale laborious and wasteful. Herein, we demonstrate that several reactions can be telescoped into a single continuous process and/or be carried out as a continuous multi-component reaction (MCR), by twin screw extrusion (TSE), in the complete absence of solvent.

Continuous multi-step synthesis by extrusion – telescoping solvent-free reactions for greater efficiency

Chemical manufacturing typically requires more than one step, involving multiple batch processes, which makes synthesis at scale laborious and wasteful. Herein, we demonstrate that several reactions can be telescoped into a single continuous process and/or be carried out as a continuous...

pubs.rsc.org

No, I realize what it means in chemistry. I thought maybe it was being used in some other manner, b/c there's really not much to telescope in the case of MDMA production from the starting points of PMK or PMK glycidate, or arguably even isosafrole, safrole or heliotropin.

One-pots often suffer from shitty yields though and still require work up. EDIT: I do of course realize that we're talking about solventless techniques; but what's the evidence that we're seeing this on the clandestine level in 2025?

 

[vash445]

No, I realize what it means in chemistry. I thought maybe it was being used in some other manner, b/c there's really not much to telescope in the case of MDMA production from the starting points of PMK or PMK glycidate, or arguably even isosafrole, safrole or heliotropin.

One-pots often suffer from shitty yields though and still require work up. EDIT: I do of course realize that we're talking about solventless techniques; but what's the evidence that we're seeing this on the clandestine level in 2025?

I don't but a lot of new work ups at least end of 2024 starting becoming more popular?